The Cafe au-lait Macules and its importance, a Review.
Las maculas cafe con leche y su importancia, Revision.
EDITORIAL ENGLISH
==================
Hello friends of the network, DERMAGIC EXPRESS brings you a very interesting review today: THE CAFE AU-LAIT MACULES (CALMs), also called "BROWN SPOTS" and "LENTIGINOUS SPOTS OR MACULES". The word comes from the French "COFFEE with MILK" and refers to the light brown color of the same.
These macules can be of congenital origin or present in the first years of life, do not disappear and can increase in size and number over time. They are typically light brown, oval, and may appear anywhere on the body.
These macules may NOT MEAN ANYTHING IMPORTANT in children who present them, but in many cases may be the warning of DISEASES that have been described associated with them, among which they stand out:
1.) VON RECKLINGHAUNSEN'S NEUROFIBROMATOSIS.
2.) FANCONI ANEMIA.
3.) BANNAYAN-RILEY-RUVALCABA SYNDROME.
4.) MULTIPLE LENTIGIN SYNDROME.
5.) LEOPARD SYNDROME.
6.) NOONAN SYNDROME.
7.) ALBRIGHT SYNDROME.
8.) McCUNE-ALBRIGHT SYNDROME.
9.) ATAXIA-TELANGIECTASIA.
10.) TUBEROUS SCLEROSIS (BOURNEVILLE DISEASE).
11.) SILVER-RUSELL SYNDROME.
12.) WATSON SYNDROME.
13.) NEVOIDE BASAL CELL CARCINOMA SYNDROME.
14.) LEGIUS SYNDROME.
15.) BLOOM SYNDROME.
16.) GAUCHER'S DISEASE.
17.) PULMONARY STENOSIS.
18.) WESTERHOF SYNDROME
19.) TURNER SYNDROME.
20.) COWDEN DISEASE.
21.) HUNTER'S DISEASE
22.) MAFFUCCI SYNDROME.
23.) CHEDIAK-HIGASHI SYNDROME.
24.) MULTIPLE MUCOSAL NEUROMA SYNDROME.
25.) WISKOTT-ALDRICH SYNDROME.
26.) JAFFE-CAMPANACCI SYNDROME.
27.) CONGENITAL NEVUS.
28.) AGMINATED LENTIGINOSIS.
29.) ANHYDROTIC ECTODERMAL DISYPLASIA.
30.) POLYOSTOTIC FIBROUS DYSPLASIA.
31.) PROTEUS SYNDROME.
32.) JUVENILE XANTHOGRANULOMA.
33.) GASTROINTESTINAL TRACT POLYPOSIS.
34.) DARIER'S DISEASE (KERATOSIS FOLLICULARIS)).
The most frequent of all this is NEUROFIBROMATOSIS type 1 (NF-1), through scientific studies it has been concluded that: Most patients with 6 or more CAFE AU-LAIT MACULES (CALMs) will eventually meet the criteria Of NF1, usually at 6 years of age, and this probability increases with increasing numbers and the typical morphological appearance of these.
Another diagnostic criterion for NEUROFIBROMATOSIS type 1 (NF-1) is the presence of 6 or more CAFE AU-LAIT MACULES (CALMs) and 5 mm in diameter before puberty or greater than 15 mm in diameter after puberty , But other features are necessary to diagnose NF-1, including: Lisch nodules, presence of neurofibromas, axillary efelides Crowe's sign), osseous anomalies, optic nerve glioma and antecedents of parents or siblings with neurofibromatosis.
I bring you this review, because these simple "spots" brown color in children are suddenly irrelevant, and are not associated with any disease, are only a simple "NAEVUS" congenituses that do not bring consequences.
But I leave you a "LIST" in which the CAFE AU-LAIT MACULES (CALMs) has been associated with several syndromes and diseases, and as described, most commonly, VON RECKLINGHAUSEN NEUROFIBROMATOSIS TYPE 1 (NF-1). So if your child presents these spots you should be vigilant.
In the 70 references the facts and in the attached an 8 year old boy with CAFE AU-LAIT MACULES completely healthy.
The treatment of them today is done with different types of Laser, giving good results.
Greetings to all.
Dr. Jose Lapenta.
These macules can be of congenital origin or present in the first years of life, do not disappear and can increase in size and number over time. They are typically light brown, oval, and may appear anywhere on the body.
These macules may NOT MEAN ANYTHING IMPORTANT in children who present them, but in many cases may be the warning of DISEASES that have been described associated with them, among which they stand out:
1.) VON RECKLINGHAUNSEN'S NEUROFIBROMATOSIS.
2.) FANCONI ANEMIA.
3.) BANNAYAN-RILEY-RUVALCABA SYNDROME.
4.) MULTIPLE LENTIGIN SYNDROME.
5.) LEOPARD SYNDROME.
6.) NOONAN SYNDROME.
7.) ALBRIGHT SYNDROME.
8.) McCUNE-ALBRIGHT SYNDROME.
9.) ATAXIA-TELANGIECTASIA.
10.) TUBEROUS SCLEROSIS (BOURNEVILLE DISEASE).
11.) SILVER-RUSELL SYNDROME.
12.) WATSON SYNDROME.
13.) NEVOIDE BASAL CELL CARCINOMA SYNDROME.
14.) LEGIUS SYNDROME.
15.) BLOOM SYNDROME.
16.) GAUCHER'S DISEASE.
17.) PULMONARY STENOSIS.
18.) WESTERHOF SYNDROME
19.) TURNER SYNDROME.
20.) COWDEN DISEASE.
21.) HUNTER'S DISEASE
22.) MAFFUCCI SYNDROME.
23.) CHEDIAK-HIGASHI SYNDROME.
24.) MULTIPLE MUCOSAL NEUROMA SYNDROME.
25.) WISKOTT-ALDRICH SYNDROME.
26.) JAFFE-CAMPANACCI SYNDROME.
27.) CONGENITAL NEVUS.
28.) AGMINATED LENTIGINOSIS.
29.) ANHYDROTIC ECTODERMAL DISYPLASIA.
30.) POLYOSTOTIC FIBROUS DYSPLASIA.
31.) PROTEUS SYNDROME.
32.) JUVENILE XANTHOGRANULOMA.
33.) GASTROINTESTINAL TRACT POLYPOSIS.
34.) DARIER'S DISEASE (KERATOSIS FOLLICULARIS)).
The most frequent of all this is NEUROFIBROMATOSIS type 1 (NF-1), through scientific studies it has been concluded that: Most patients with 6 or more CAFE AU-LAIT MACULES (CALMs) will eventually meet the criteria Of NF1, usually at 6 years of age, and this probability increases with increasing numbers and the typical morphological appearance of these.
Another diagnostic criterion for NEUROFIBROMATOSIS type 1 (NF-1) is the presence of 6 or more CAFE AU-LAIT MACULES (CALMs) and 5 mm in diameter before puberty or greater than 15 mm in diameter after puberty , But other features are necessary to diagnose NF-1, including: Lisch nodules, presence of neurofibromas, axillary efelides Crowe's sign), osseous anomalies, optic nerve glioma and antecedents of parents or siblings with neurofibromatosis.
I bring you this review, because these simple "spots" brown color in children are suddenly irrelevant, and are not associated with any disease, are only a simple "NAEVUS" congenituses that do not bring consequences.
But I leave you a "LIST" in which the CAFE AU-LAIT MACULES (CALMs) has been associated with several syndromes and diseases, and as described, most commonly, VON RECKLINGHAUSEN NEUROFIBROMATOSIS TYPE 1 (NF-1). So if your child presents these spots you should be vigilant.
In the 70 references the facts and in the attached an 8 year old boy with CAFE AU-LAIT MACULES completely healthy.
The treatment of them today is done with different types of Laser, giving good results.
Greetings to all.
Dr. Jose Lapenta.
EDITORIAL ESPAÑOL
==================
Hola amigos de la red, DERMAGIC EXPRESS les trae hoy una revision bastante interesante: LAS MACULAS CAFE CON LECHE, (CAFE AU-LAIT), denominadas tambien "MACULAS COLOR MARRON" y "MACULAS O MANCHAS LENTIGINOSAS". La palabra viene del frances "CAFE con LECHE) y se refiere al color marron claro de las mismas.
Esttas maculas pueden ser de origen congenito o presentarse en los primeros años de vida, no desaparecen y pueden aumentar en tamaño y numero con el tiempo. Tipicamente son de color marron claro, ovales y pueden presentarse en cualquier parte del cuerpo.
Estas maculas pueden NO SIGNIFICAR NADA DE IMPORTANCIA en los niños que las presentan, pero en muchos casos pueden ser el aviso de ENFERMEDADES que se han descrito asociadas a ellas, entre las que destacan:
1.) NEUROFIBROMATOSIS DE VON RECKLINGHAUNSEN.
2.) ANEMIA DE FANCONI.
3.) SINDROME DE BANNAYAN- RILEY-RUVALCABA.
4.) SINDROME DE LENTIGINES MULTIPLES.
5.) SINDROME DE LEOPARD.
6.) SINDROME DE NOONAN.
7.) SINDROME DE ALBRIGHT.
8.) SINDROME DE McCUNE-ALBRIGHT.
9.) ATAXIA-TELANGIECTASIA.
10.) ESCLEROSIS TUBEROSA (ENFERMEDAD DE BOURNEVILLE).
11.) SINDROME DE SILVER-RUSELL.
12.) SINDROME DE WATSON.
13.) SINDROME DEL CARCINOMA BASO CELULAR NEVOIDE.
14.) SINDROME DE LEGIUS.
15.) SINDROME DE BLOOM.
16.) ENFERMEDAD DE GAUCHER.
17.) ESTENOSIS PULMONAR.
18.) SINDROME DE WESTERHOF
19.) SINDROME DE TURNER.
20.) ENFERMEDAD DE COWDEN.
21.) ENFERMEDAD DE HUNTER
22.) SINDROME DE MAFFUCCI.
23.) SINDROME DE CHEDIAK-HIGASHI.
24.) SINDROME DEL NEUROMA MUCOSA MULTIPLE.
25.) SINDROME DE WISKOTT-ALDRICH.
26.) SINDROME DE JAFFE-CAMPANACCI.
27.) NEVUS CONGENITO.
28.) LENTIGINOSIS AGUDIZADA.
29.) DISPLASIA ECTODERMICA ANHIDROTICA.
30.) DISPLASIA FIBROSA POLIOSTOTICA.
31.) SINDROME DE PROTEUS.
32.) XANTOGRANULOMA JUVENIL.
33.) POLIPOS DEL TRACTO GASTRO INTESTINAL.
34.) ENFERMEDAD DE DARIER (QUERATOSIS FOLICULAR).
La mas frecuente de todas esta es la NEUROFIBROMATOSIS tipo 1 (NF-1), mediante estudios cientificos se ha llegado a la conclusion que: La mayoría de los pacientes con 6 o más MACULAS CAFE CON LECHE (CALMs) con el tiempo cumplirá los criterios de diagnóstico de NF1, por lo general a los 6 años de edad, y esta probabilidad aumenta con el aumento del número y la apariencia morfológica típica de estas.
Otro criterio diagnostico para la NEUROFIBROMATOSIS tipo 1 (NF-1) es la presencia de 6 o mas maculas CAFE CON LECHE(CALMs) y con tamaño 5 mm de diámetro antes de la pubertad, o mayores de 15 mm de diámetro después de la pubertad, pero otras características son necesarias para diagnosticar NF-1, entre ellas: Nodulos de Lisch, presencia de neurofibromas, efelides axilares (signo de Crowe), anomalias oseas, glioma del nervio optico y antecedentes de padres o hermanos con neurofibromatosis.
Te traigo esta revision, porque estas simples "MANCHAS" color marron en los niños, de pronto son irrelevantes, y no estan asociada a ninguna enfermedad, es decir, son "LUNARES"
congenitos que no traen consecuencias.
Pero te dejo una "LISTA" en las que se ha asociado LAS MACULAS CAFE CON LECHE con varios sindromes y enfermedades, y como describi, la mas comun, la NEUROFIBROMATOSIS DE VON RECKLINGHAUSEN TIPO 1 (NF-1). De modo que si tu niño presenta estas maculas debes estar vigilante.
En las 70 referencias los hechos y en el adjunto un niño de 8 años con MACULAS CAFE CON LECHE completamente sano.
El tratamiento de ellas hoy dia se hace con diverso tipos de Laser, dando buenos resultados.
Saludos a todos.
Dr. Jose Lapenta.
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REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES
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1.) Multiple lentigines syndrome (LEOPARD syndrome or progressive cardiomyopathic lentiginosis).
2.) Multiple facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1.
3.) [Neurofibromatosis type 1: a survey of 195 patients]
4.) Darier's disease associated with multiple cafe-au-lait macules.
5.) Pigmentary anomalies in the multiple lentigines syndrome: Is it distinct from
LEOPARD syndrome?
6.) Long-term follow-up in treatment of solar lentigo and cafe-au-lait macules with Q-switched ruby laser.
7.) Skin abnormalities in neurofibromatosis 2.
8.) Segmental neurofibromatosis: case reports and review.
9.) Recurrent ovarian cyst and mutation of the Gs alpha gene in ovarian cyst fluid cells: what is the link with McCune-Albright syndrome?
10.) Familial multiple cafe au lait spots.
11.) Diagnostic outcome in children with multiple cafe au lait spots.
12.) Cutaneous nerves in cafe au lait spots with white halos in
infants with neurofibromatosis. An electron microscopic study.
13.) McCune-Albright syndrome with multiple bilateral cafe au lait spots.
14.) Radiosensitivity of fibroblasts obtained from a cafe-au-lait spot and normal-appearing skin of a patient with neurofibromatosis (NF-6).
15.) A computed image analyzing system for quantitation of
melanocyte morphology in cafe-au-lait macules of neurofibromatosis.
16.) Prevalence of congenital-nevus-like nevi, nevi spili, and cafe au lait spots.
17.) Congenital-nevus-like nevi, nevi spili, and cafe-au-lait spots in patients with malignant melanoma.
18.) Cafe-au-lait spots in schoolchildren.
19.) Cafe au lait spots in ataxia-telangiectasia (A.T.).
20.) "Sunburn" freckles, cafe-au-lait macules, and other pigmented lesions of schoolchildren: the Vancouver Mole Study.
21.) Melanotic macules following Blaschko's lines in McCune-Albright syndrome.
22.) Treatment of benign pigmented epidermal lesions by Q-switched ruby laser.
23.) 510-nm pigmented lesion dye laser. Its characteristics and clinical uses.
24.) McCune-Albright syndrome: how many endocrinopathies can one patient have?
25.) Aspects in neurofibromatosis from the viewpoint of dermatology.
26.) [Unilateral lentiginosis--a segmental neurofibromatosis without neurofibromas]
27.) Non-von Recklinghausen's neurofibromatosis presenting as hemifacial neurofibromas and contralateral cafe au lait spots.
28.) The prevalence of cafe-au-lait patches in tuberous sclerosis.
29.) Common and uncommon cutaneous findings in patients with ataxia-telangiectasia.
30.) [Diagnostic value of cafe-au-lait spots (author's transl)]
31.) The eastern Australian childhood nevus study: prevalence of atypical nevi, congenital nevus-like nevi, and other pigmented lesions.
32.) [Von Recklinghausen neurofibromatosis and dermal melanocytic nevi]
33.) Fanconi anemia.
34.) Treatment of epidermal pigmented lesions with the frequency-doubled Q-switched Nd:YAG laser. A controlled, single-impact, dose-response, multicenter trial.
35.) Agminated lentiginosis: case report and review of the literature.
36.) Cutaneous melanoma in a patient with neurofibromatosis: a case report and review of the literature.
37.) [Type 1 neurofibromatosis in Tunisia: 66 cases]
38.) Bilateral pheochromocytoma-ganglioneuroma of the adrenal in type 1 neurofibromatosis.
39.) Laser treatment of benign pigmented epidermal lesions using a 300 nsecond pulse and 510 nm wavelength.
40.) Segmental neurofibromatosis with only macular lesions.
41.) Preliminary experience with a flashlamp-pulsed tunable dye laser for treatment of benign pigmented lesions.
42.) Unusual cutaneous manifestations of anhidrotic ectodermal dysplasia--a case report.
43.) Polyostotic fibrous dysplasia associated with extensive linear epidermal naevi.
44.) The diagnosis of neurofibromatosis-1 in the child under the age of 6 years.
45.) Effect of wavelength on cutaneous pigment using pulsed irradiation.
46.) Pigmentary disorders in oriental skin.
47.) [Cutaneous signs of Noonan's syndrome. Apropos of a case with ulerythema ophyogenes, disseminated pilar and sudoral keratosis and progressive alopecia]
48.) Neurofibromatosis and Albright's syndrome.
49.) The Proteus syndrome: the Elephant Man diagnosed.
50.) Juvenile xanthogranuloma: an analysis of 45 cases by clinical follow-up, light- and electron microscopy.
51.) [Several cases of non-phlebologic pigmentation of the lower extremities]
52.) Multiple agminated spindle cell nevi: unique clinical presentation and review.
53.) The invisible dermatoses.
54.) Principles of genetics as related to the chromosome disorders and congenital malformations with reference to prenatal diagnosis and genetic counseling.
55.) Juvenile chronic granulocytic leukemia: emphasis on cutaneous manifestations and underlying neurofibromatosis.
56.) The removal of cutaneous pigmented lesions with the Q-switched ruby laser and the Q-switched neodymium: yttrium-aluminum-garnet laser. A comparative study.
57.) [Smooth muscle hamartoma: anatomoclinical characteristics and nosological limits] 58.) Multiple café au lait spots in familial patients with MAP2K2 mutation.
59.) A severe form of Noonan syndrome and autosomal dominant café-au-lait spots - evidence for different genetic origins.
60.) The diagnostic and clinical significance of café-au-lait macules.
61.) A girl with cutaneous hyperpigmentation, café au lait spots and ring chromosome 15 without significant deletion.
62.) Diagnostic outcome in children with multiple café au lait spots.
63.) Café au lait macules and juvénile polyps.
64.) Café-au-lait spots in neurofibromatosis type 1 and in healthy control individuals: hyperpigmentation of a different kind?
65.) Cafe au lait has hue of its own.
66.) Predictive value of café au lait macules at initial consultation in the diagnosis of neurofibromatosis type 1.
67.) Nevoid basal cell carcinoma syndrome presenting with neck pits and café au lait patches.
68.) Divided café-au-lait macule of the mouth.
69.) Molecular screening strategies for NF1-like syndromes with café-au-lait macules (Review).
70.) The first Slovak Legius syndrome patient carrying the SPRED1 gene mutation.
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1.) Multiple lentigines syndrome (LEOPARD syndrome or progressive cardiomyopathic
lentiginosis).
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Coppin BD; Temple IK
Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
J Med Genet (ENGLAND) Jul 1997 34 (7) p582-6 ISSN: 0022-2593
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9711
Subfile: INDEX MEDICUS
The multiple lentigines syndrome is an autosomal dominant condition which has many
similarities to Noonan syndrome, except in the most striking feature from which its
name is derived. The less neutral but very apt mnemonic, LEOPARD syndrome, was first
used by Gorlin et al to whom the major debt in the definition of this syndrome lies,
that is, Lentigines, ECG abnormalities, Ocular hypertelorism/Obstructive
cardiomyopathy, Pulmonary valve stenosis, Abnormalities of genitalia in males,
Retardation of growth, and Deafness. Not previously included in the mnemonic is
cardiomyopathy which is an important feature because it is associated with
significant mortality.
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2.) Multiple facial angiofibromas and collagenomas in patients with multiple endocrine
neoplasia type 1.
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Darling TN; Skarulis MC; Steinberg SM; Marx SJ; Spiegel AM; Turner M
Dermatology Branch, National Cancer Institute, National Institutes of Health
Bethesda, MD, USA.
Arch Dermatol (UNITED STATES) Jul 1997 133 (7) p853-7 ISSN: 0003-987X
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9710
Subfile: AIM; INDEX MEDICUS
OBJECTIVES: To evaluate patients with multiple endocrine neoplasia type 1 (MEN 1)
for cutaneous manifestations. DESIGN: Survey during a 3-year period. SETTING: The
National Institutes of Health, a tertiary referral research hospital in Bethesda Md.
PATIENTS: A consecutive sample of 32 individuals with previously diagnosed MEN1 who
were not preselected for the presence of skin lesions were examined for cutaneous
abnormalities. None of the patients or family members were diagnosed as having
tuberous sclerosis. INTERVENTIONS: Lesions were identified by clinical appearance,
photographed, and confirmed histologically. MAIN OUTCOME MEASURE: To determine the
frequency of skin lesions in patients with MEN1. RESULTS: Multiple facial
angiofibromas were observed in 28 (88%) of the patients with MEN1, with 16 patients
(50%) having 5 or more. Angiofibromas were clinically and histologically identical
to those in individuals with tuberous sclerosis. Collagenomas were observed in 23
patients (72%). Also observed were cafe au lait macules in 12 patients (38%),
lipomas in 11 patients (34%), confetti-like hypopigmented macules in 2 patients (6%),
and multiple gingival papules in 2 patients (6%). CONCLUSIONS: Multiple
angiofibromas, collagenomas, lipomas, confetti-like hypopigmented macules and
multiple gingival papules are cutaneous manifestations of MEN1 and should be looked
for in both family members of patients with MEN1 and individuals with
hyperparathyroidism of other MEN1-associated tumors. Multiple angiofibromas can no
longer be considered pathognomonic for tuberous sclerosis. The observation of
angiofibromas in individuals without tuberous sclerosis necessitates further
biochemical testing for MEN1.
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3.) [Neurofibromatosis type 1: a survey of 195 patients]
Neurofibromatosis type 1: een overzicht van 196 patienten.
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Overweg-Plandsoen WC; Weersink RG; Sillevis Smitt JH; Fleury P; van Asperen CJ
Afd. Neurologie en Kindergeneeskunde, Academisch Medisch Centrum, Amsterdam.
Ned Tijdschr Geneeskd (NETHERLANDS) Mar 29 1997 141 (13) p624-9 ISSN: 0028-2162
Language: DUTCH Summary Language: ENGLISH
Document Type:
JOURNAL ARTICLE English Abstract
Journal Announcement: 9708
Subfile: INDEX MEDICUS
OBJECTIVE: To analyse symptoms and complications in patients with neurofibromatosis
type 1 (NF1). All patients were examined in a multidisciplinary outpatient
neurofibromatosis clinic during a period of 10 years. DESIGN: Retrospective.
SETTING: Academic Medical Center, University Hospital Amsterdam, the Netherlands.
METHOD: All data on 450 persons visiting the neurofibromatosis clinic were stored in
a database. Data were collected on the results of dermatological, neurological,
ophthalmological and general examinations and on family history. For this study the
follow-up data of 196 patients with a definite diagnosis of 'NF1' were analysed.
RESULTS: In childhood diagnosis NF1 is predominantly based on specific dermatological
symptoms such as > 6 cafe-au-lait (CAL) spots and freckling and on the presence of
characteristic ophthalmological signs as two or more Lisch nodules. In this study
the frequencies of these symptoms were 98% (CAL). 92% (freckles), and 93% (Lisch
nodules) respectively. The frequencies of well-known complications of this disorder
are comparable with the literature findings. In this study we found optic pathway
glioma (OPG) in 10%, macrocephaly in 36%, hydrocephalus in 5%, retardation in 14%,
brain tumours in 5%, kyphoscoliosis in 13%. renal artery stenosis in 0.5% and
neurofibrosarcoma in 0.5% of NF1 patients. In children the degree of severity of
this disorder is less than in adults, demonstrating the progressive character of the
disease. CONCLUSION: The diagnosis of 'NF1' can usually be made by dermatological
and ophthalmological examination. In case of a definite diagnosis in childhood
regular follow-up is recommended since severe complications, such as OPG and
kyphoscoliosis, may occur specifically in childhood and adolescence. For adult
patients determination of the degree of severity is essential for the decision
whether or not they need regular follow-up; they should have their blood pressure
measured annually.
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4.) Darier's disease associated with multiple cafe-au-lait macules.
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Soroush V; Gurevitch AW
UCLA School of Medicine, Harbor-UCLA Medical Center, Department of Medicine,
Torrance 90509, USA.
Cutis (UNITED STATES) Apr 1997 59 (4) p193-5 ISSN: 0011-4162
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9708
Subfile: INDEX MEDICUS
Darier's disease, or keratosis follicularis, is an autosomal dominant inherited
skin disease characterized by keratotic papules predominantly on the upper trunk and
scalp, palmar pits, and nail dystrophy. It has been reported in association with
basal cell carcinoma and other skin cancers, neuropsychiatric disorders, salivary
gland obstruction, renal and testicular agenesis, bone cysts, and psoriasis. We
describe the first report of a patient with multiple cafe-au-lait macules, but no
personal or family history of neurofibromatosis, who developed Darier's disease.
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5.) Pigmentary anomalies in the multiple lentigines syndrome: Is it distinct from
LEOPARD syndrome?
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Arnsmeier SL; Paller AS
Department of Pediatrics, Children's Memorial Medical Center, Northwestern
University Medical School, Chicago, Illinois, USA.
Pediatr Dermatol (UNITED STATES) Mar-Apr 1996 13 (2) p100-4 ISSN: 0736-8046
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9706
Subfile: INDEX MEDICUS
We observed 2 families with 26 individuals affected by multiple lentigines syndrome
(MLS). All patients had extensive generalized lentigines, including in the axillary
and inguinal regions, diffuse hyperpigmentation, hypopigmented patches, and
hyperpigmented patches, many of which appeared clinically to be cafe au lait spots.
Multiple lentigines syndrome should be considered in the differential diagnosis of
multiple cafe au lait spots in children, particularly since the spots are usually
present before the lentigines develop and may be clinically indistinguishable from
the cafe au lait spots of neurofibromatosis. No significant noncutaneous features
occurred in the two families with three generations of affected individuals,
suggesting that MLS is a distinct entity. However, patients with the noncutaneous
abnormalities of the LEOPARD syndrome have been described in families in which most
members had pigmentary lesions only. Therefore, patients with multiple lentigines
should be evaluated for noncutaneous abnormalities, particularly hearing loss and
cardiac anomalies. Similarly, until investigators demonstrate lack of genetic
linkage between MLS and LEOPARD syndrome, genetic counseling of patients affected by
the cutaneous features of the former should include the potential for noncutaneous
features in offspring.
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6.) Long-term follow-up in treatment of solar lentigo and cafe-au-lait macules with Q-switched ruby laser.
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AU: Shimbashi-T; Kamide-R; Hashimoto-T
AD: Tokyo, Japan.
SO: Aesthetic-Plast-Surg. 1997 Nov-Dec; 21(6): 445-8
ISSN: 0364-216X
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: A Q-switched ruby laser was used for treatment of 10 patients with solar lentigo and 12 patients with cafe-au-lait macules. In this study, the lesions were treated with the laser at a rate of 6 J/cm2. The patients were observed for 10-21 months with an average of 13.8 months after the final session. Solar lentigos were treated once or twice, and the response rate was 70%. Cafe-au-lait macules were treated one to six times, and the response rate was 33%. Side effects, such as hyperpigmentation and scar formation, were rarely seen. Therefore, Q-switched ruby laser treatment is an effective treatment for epidermal pigmented lesions; however, in patients with cafe-au-lait macules, the responses to the treatment varied, and a repigmentation was seen in 50% of these patients. Thus, long-term follow-up is required for patients with cafe-au-lait macules.
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7.) Skin abnormalities in neurofibromatosis 2.
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AU: Mautner-VF; Lindenau-M; Baser-ME; Kluwe-L; Gottschalk-J
AD: Neurology Department, Allgemeines Krankenhaus Ochsenzoll, Heidlberg, Germany.
SO: Arch-Dermatol. 1997 Dec; 133(12): 1539-43
ISSN: 0003-987X
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: OBJECTIVE: To determine the prevalence, distribution, and histopathological conditions of skin abnormalities in neurofibromatosis 2 (NF2). DESIGN: Case series. SETTING: Hospital neurology department. PATIENTS: Consecutive sample of 88 patients with NF2 referred through workshops and publications, genetic counseling, and referral from neurosurgical departments; 81 patients met the National Institutes of Health, Bethesda, Md, NF2 diagnostic criteria and the diagnosis was established by mutation or segregation analyses in 7 patients. MAIN OUTCOME MEASURES: Prevalence, distribution, and type of skin abnormalities; histopathological features of 29 skin tumors selected primarily for medical indications. RESULTS: Fifty-two patients (59.1%) had 458 skin tumors, which were the first presenting sign in 27.3% of patients and usually appeared as flat dysplastic tumors or subcutaneous spherical nodular tumors of the peripheral nerves, on the limbs and trunk. Although 29 patients (33.0%) had cafe au lait spots, only 2 patients had as many as 6 spots. compared with patients with milder disease, patients with more severe disease had a significantly greater prevalence of skin tumors (24.0% and 71.0%, P < .001), more than 10 skin tumors (0.0% and 27.4%, P = .004), flat dysplastic skin tumors (8.0% and 54.8%, P < .001), and subcutaneous spherical nodular tumors (24.0% and 58.1%, P = .004). The histologically analyzed tumors were predominantly schwannomas, but 5 were neurofibromas and 2 were mixed tumors. CONCLUSIONS: The prevalence of some skin tumor types in NF2 is high and varies with disease severity, and schwannomas predominate in sampled tumors. The occurrence of neurofibromas is surprising, but could be explained by an interaction between neurofibromin and the NF2 gene product in regulating the ras proto-oncogene.
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8.) Segmental neurofibromatosis: case reports and review.
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AU: Hager-CM; Cohen-PR; Tschen-JA
AD: Department of Dermatology, Universitat zu Koln, Germany.
SO: J-Am-Acad-Dermatol. 1997 Nov; 37(5 Pt 2): 864-9
ISSN: 0190-9622
PY: 1997
LA: ENGLISH
CP: UNITED-STATES
AB: Segmental neurofibromatosis (neurofibromatosis type V) is a rare disorder characterized by cafe-lu-lait macules and neurofibromas, or only neurofibromas, limited to one region of the body. Three patients with segmental neurofibromatosis are described, and cases of this condition in the world literature are reviewed. Segmental neurofibromatosis has only been described in 82 patients, including our three. The median age at onset was 28 years and the incidence was higher in women (58%). The neurofibromas most commonly occupied either a cervical or thoracic dermatome and were unilateral, occurring more often on the right side (43 patients) than the left (34 patients). Cafe-au-lait macules were present in 26% of patients. Axillary freckling was described in only nine patients. Disease-associated systemic involvement was uncommon. Most patients with segmental neurofibromatosis (93%) do not have a family history of neurofibromatosis.
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9.) Recurrent ovarian cyst and mutation of the Gs alpha gene in ovarian cyst fluid cells: what is the link with McCune-Albright syndrome?
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AU: Pienkowski-C; Lumbroso-S; Bieth-E; Sultan-C; Rochiccioli-P; Tauber-M
AD: Unite d'Endocrinologie et de Genetique Medicale, Service de Pediatrie, Toulouse, France.
SO: Acta-Paediatr. 1997 Sep; 86(9): 1019-21
ISSN: 0803-5253
PY: 1997
LA: ENGLISH
CP: NORWAY
AB: Isolated peripheral precocious puberty due to recurrent ovarian cysts evokes a McCune-Albright syndrome (MAS). This syndrome associates endocrine dysfunction such as precocious puberty, polyostotic fibrous dysplasia, and "cafe-au-lait" skin lesions. We report the case of a 3-y-old girl who presented with peripheral puberty with extremely elevated oestradiol level, low LH and FSH levels, and an ovarian cyst that quickly resolved. Skeletal X-rays were normal and she had no cafe-au-lait spots. GnRH analogue treatment was ineffective. A second ovarian cyst appeared and was completely drained under ultrasonographic guidance. Molecular biological analysis performed on fluid cells revealed the Arg201-->His mutation of the Gs alpha gene described in MAS. Percutaneous aspiration of simple ovarian cyst to detect "MAS" mutation is of interest in the diagnosis of recurrent ovarian cyst.
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10.) Familial multiple cafe au lait spots.
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SO - Arch Dermatol 1994 Nov;130(11):1425-6
AU - Arnsmeier SL; Riccardi VM; Paller AS
PT - JOURNAL ARTICLE
AB - BACKGROUND: Familial multiple cafe au lait spots (CLS) represent a rare, autosomal dominant pigmentary disorder characterized by the multiple CLS seen in neurofibromatosis type 1 (NF-1) but differing from NF-1 by the absence of neurofibromas and other neural crest tumors. OBSERVATIONS: We describe multiple CLS in 12 patients from three families, each with at least two generations of affected adults. The clinical presentation was consistent within families. In one family, the CLS were accompanied by axillary and inguinal freckling and Lisch nodules. Otherwise, none of the 12 patients had neurofibromas or noncutaneous manifestations of NF-1. CONCLUSIONS: These families provide further evidence that patients may have multiple CLS, with or without axillary freckling or Lisch nodules, and yet not have NF-1. Care must be taken when counseling families with CLS that the diagnosis of NF-1, with its many associated potential problems, is not made erroneously. Studies of the gene mutation(s) of patients with familial multiple CLS are needed to distinguish NF-1 and familial multiple CLS as distinct disorders.
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11.) Diagnostic outcome in children with multiple cafe au lait spots.
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SO - Pediatrics 1992 Dec;90(6):924-7
AU - Korf BR
PT - JOURNAL ARTICLE
AB - Forty-one children, ranging in age from 1 month to 14 years, had six or more cafe au lait spots at their initial visit and were examined annually. Signs of neurofibromatosis type 1 eventually developed in 24. The most common feature to appear to confirm the diagnosis was skin-fold freckling, which occurred in 18 subjects. Diagnosis was based on the appearance of Lisch nodules in 5, and on neurofibromas in 3. In most instances, diagnosis was established within 3 years of initial evaluation, usually before 5 years of age. Six children had a segmental distribution of cafe au lait spots, suggesting segmental neurofibromatosis. In 3, diagnoses other than neurofibromatosis type 1 were established (Bannayan-Riley-Rulvalcaba syndrome, multiple lentigines syndrome, and fibrous dysplasia). In 8 subjects only multiple cafe au lait spots are present, and no definite diagnosis has been established. It is concluded that with regular follow-up, including physical and ophthalmological examinations, a definite diagnosis, most commonly neurofibromatosis type 1, can be established for most children having multiple cafe au lait spots.
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12.) Cutaneous nerves in cafe au lait spots with white halos in
infants with neurofibromatosis. An electron microscopic study.
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SO - Arch Dermatol 1992 Jul;128(7):957-61
AU - Mihara M; Nakayama H; Aki T; Inoue T; Shimao S
PT - JOURNAL ARTICLE
AB - BACKGROUND AND DESIGN--Although two cardinal skin manifestations of neurofibromatosis are cutaneous neurofibromas and cafe au lait spots, the pathogenesis of cafe au lait spots are very poorly known compared with that of cutaneous neurofibromas. Thus, the cafe au lait spots in two Japanese infants were clinically, histologically, and electron-microscopically investigated. OBSERVATIONS--Some of the cafe au lait spots in the mongolian spots were surrounded by white halos. Histologically, in the cafe au lait spots, the epidermal basal cells had abundant melanin pigment, but macromelanosomes were not seen throughout the epidermis. In the white halo, the epidermal basal cells had a small amount of melanin pigment. Electron microscopically, the cafe au lait spots and their white halos had many subepidermal and intraepidermal nerves that belonged to free nerve endings. All the cutaneous nerves were mature. Some of the intraepidermal nerves had partially or completely naked axons that contacted tightly with the cytomembranes of the basal keratinocytes. Some of the axons in the subepidermal nerves showed degenerative changes only in the white halos. No ultrastructural pathologic changes were observed in the melanocytes, the epidermal keratinocytes, or melanosomes in those cells in the cafe au lait spots and their white halos; also, dermal melanocytes were absent in the both areas. CONCLUSIONS--The increase of the cutaneous nerves and the absence of dermal melanocytes in the cafe au lait spots and their white halos may be considered as characteristic histologic cutaneous findings in infants with neurofibromatosis. However, no evidence indicates that the cutaneous nerves may participate closely in the pathogenesis of the white halos.
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13.) McCune-Albright syndrome with multiple bilateral cafe au lait spots.
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SO - Pediatr Dermatol 1991 Mar;8(1):35-9
AU - Roth JG; Esterly NB
PT - JOURNAL ARTICLE
AB - A 7-week-old infant developed hyperpigmented lesions at 5 days of age that gradually progressed to sharply demarcated, medium-brown macules of unusual configuration involving the neck, trunk, buttocks, upper arms, and right upper thigh. A biopsy specimen of a representative lesion showed changes of epidermal melanosis consistent with cafe au lait spot. At age 15 months the patient developed a limp. Roentgenographic evaluation showed widespread, bilateral changes of fibrous dysplasia, most severe in the right pelvis, femur, and tibia. At the present time he has no evidence of precocious puberty or other endocrinopathies. Despite the absence of endocrine abnormalities, these findings are consistent with a diagnosis of McCune-Albright syndrome with extensive bony and cutaneous lesions.
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14.) Radiosensitivity of fibroblasts obtained from a cafe-au-lait spot and normal-appearing skin of a patient with neurofibromatosis (NF-6).
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SO - Cancer Genet Cytogenet 1990 Jul 15;47(2):191-6
AU - Hannan MA; Smith BP; Sigut D; Sackey K
PT - JOURNAL ARTICLE
AB - Fibroblast cells derived from a cafe-au-lait spot and normal-appearing skin of a neurofibromatosis (NF-6) patient were studied for radiosensitivity in comparison with two normal cell lines used as "controls." No difference in radiosensitivity was observed between the patient's cell lines and the controls using acute gamma-irradiation. However, a markedly increased radiosensitivity of the fibroblasts obtained from the patient's skin of normal appearance was demonstrated after chronic gamma-irradiation. The cells from the cafe-au-lait spot showed intermediate sensitivity to chronic irradiation as compared with the control cell lines and the fibroblasts derived from the normal skin of the patient. These results showed the usefulness of chronic irradiation in detecting increased cellular radiosensitivity which may result from a unique DNA repair defect in an NF patient. We suggest that enhanced genetic changes in radiosensitive NF patients may lead to formation of cafe-au-lait lesions and certain tumors. Such a transformation may be associated with production of radiotolerant cells.
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15.) A computed image analyzing system for quantitation of
melanocyte morphology in cafe-au-lait macules of neurofibromatosis.
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SO - J Invest Dermatol 1987 Mar;88(3):287-91
AU - Ishida O; Jimbow K
PT - JOURNAL ARTICLE
AB - Split-dopa preparation is a commonly used technique to visualize the epidermal melanocytes. It can characterize the number of melanocytes and their tyrosinase (dopa-oxidase) activities. There is not, however, any method to quantitate the morphologic changes of dopa-positive melanocytes in the split preparation. This study designed a computed image analyzing system and evaluated the structure of epidermal melanocytes in cafe-au-lait macules with comparison to normally pigmented skin in 5 patients with neurofibromatosis. By this method we were able to delineate the melanocyte structure with melanocyte population and coloration of the macules. We found that the population and structure of melanocytes differ greatly depending on the coloration of the cafe-au-lait macules. The light brown and brown macules showed the normal population of melanocytes with an increase in the area and perimeter of whole cell; the area, perimeter, and diameter of cytoplasm; and the area, length, and breadth of dendrites. In contrast, the dark brown macules revealed a significant increase of the epidermal melanocytes with a decrease in all of these parameters. Thus, the methodologic design presented here may enable a quantitative, two-dimensional analysis of melanocyte structure at the light microscopic level in the normal skin and in various pigmentary disorders.
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16.) Prevalence of congenital-nevus-like nevi, nevi spili, and cafe au lait spots.
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SO - Arch Dermatol 1985 Jun;121(6):766-9
AU - Kopf AW; Levine LJ; Rigel DS; Friedman RJ; Levenstein M
PT - JOURNAL ARTICLE
AB - To determine the clinical prevalence of medium-sized (1.5- to 19.9-cm-diameter) congenital-nevus-like nevi (CNLN), a consecutive series of 601 patients (mostly adults) had total cutaneous examinations. In this series, 15 (2.5%) were found to have such lesions. In addition, 14 (2.3%) had nevi spili and 83 (13.8%) had cafe au lait spots. All three types of lesions were equally represented in both sexes and tended to spare the head, neck, and upper extremities. Compared with CNLN, nevi spili were found to have significantly larger diameters and lower mean age, suggesting that these are different types of lesions. Some recommend the surgical removal of all congenital nevocytic nevi because of their malignant potential. Since it is not possible to clinically distinguish congenital nevocytic nevi and CNLN and since the observed prevalence of these lesions in adults is over four times that previously reported in newborns, such a recommendation becomes less feasible.
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17.) Congenital-nevus-like nevi, nevi spili, and cafe-au-lait spots in patients with malignant melanoma.
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SO - J Dermatol Surg Oncol 1985 Mar;11(3):275-80
AU - Kopf AW; Levine LJ; Rigel DS; Friedman RJ; Levenstein M
PT - JOURNAL ARTICLE
AB - The prevalence of congenital-nevus-like nevi (CNLN) in a group of 105 adults who had malignant melanoma (MM) was compared with that in a control group of 601 adults not afflicted by MM. Total cutaneous examinations were performed on both groups. The control group presented with complaints other than pigmented lesions. In this series, 10 (9.5%) of the group with MM had clinically diagnosed CNLN 1.5 cm or larger in diameter. These CNLN were not in contiguity with the MM sites. The 9.5% prevalence of CNLN in the group with MM was significantly higher (p less than 0.005) than the 2.5% CNLN observed in the control population. None of the patients in either group had large congenital nevocytic nevi (greater than or equal to 20 cm). In addition, in the group with MM, 5 patients (4.8%) had nevi spili (NS) and 13 (12.4%) had cafe-au-lait spots (CLS). The prevalence rates for these two types of pigmented lesions were not significantly different from those observed in the nonmelanoma control group (2.3% for NS; 13.8% for CLS). The relative risk for developing MM is 4.1 in people with CNLN compared with those without CNLN, which indicates that these nevi may be markers for individuals prone to develop malignant melanoma.
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18.) Cafe-au-lait spots in schoolchildren.
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SO - Arch Dis Child 1982 Aug;57(8):631-2
AU - Burwell RG; James NJ; Johnston DI
PT - JOURNAL ARTICLE
AB - This paper reports a study of cafe-au-lait spots of a minimum diameter of 1 cm in 732 white schoolchildren. Three groups were identified, according to the number of cafe-au-lait spots on each child: (1) those with none (74%), (2) those with fewer than 5 (25%), and (3) those with at least 5 (5 children, 2 considered to be normal, and 3 siblings each presumed to have neurofibromatosis, one having died from leukaemia). Excluding the last group, the number of cafe-au-lait spots in the sample was not significantly related to age or sex. Some support is given for using the number of cafe-au-lait spots as an empirical threshold to diagnose neurofibromatosis.
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19.) Cafe au lait spots in ataxia-telangiectasia (A.T.). ====================================================================
Histochemical and ultrastructural study in one case.
SO - Arch Dermatol Res 1980;268(1):91-9
AU - Ortonne JP; Claudy AL; Freycon F
PT - JOURNAL ARTICLE
AB - Cafe au lait spots appear to represent one of the cutaneous features of Ataxia-telangiectasia (A.T.). At the cellular level, they are characterized by an epidermal hypermelanosis with a normal number of melanocytes. At the subcellular level, two basic abnormalities are observed: (1) an increase in the synthesis of melanosomes; (2) a modification of their distribution within the epidermal keratinocytes. Numerous pendulous melanocytes project into the upper dermis. Altered melanocytes are also observed. These show mitochondrial dilatation, melanosomal autophagic vacuoles, as well as lipid droplets. These abnormalities are not observed in the normal surrounding skin. The significance of these observations is discussed and stress is placed on the difficulty in establishing a differential diagnosis of cafe au lait spots, based on their histoenzymological and ultrastructural features.
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20.) "Sunburn" freckles, cafe-au-lait macules, and other pigmented lesions of schoolchildren: the Vancouver Mole Study.
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SO - J Am Acad Dermatol 1995 Apr;32(4):565-70
AU - McLean DI; Gallagher RP
PT - JOURNAL ARTICLE
AB - BACKGROUND: Relatively few studies have evaluated the prevalence of pigmented lesions in children. OBJECTIVE: We assessed the prevalence and constitutional correlates of "sunburn" freckles, cafe-au-lait macules, congenital nevi, and several other pigmented lesions. METHODS: Six specially trained nurses examined 1592 Vancouver schoolchildren, 6 to 18 years old, under uniform lighting conditions and counted all pigmented lesions except those on the genitals, buttocks, and breasts in girls. RESULTS: In the 1146 white children of European origin, 378 Asian children, and 68 Indo-Pakistani children, the prevalence of one or more cafe-au-lait macules was essentially equivalent (28%). The prevalence of Becker's nevus, nevus spilus, and congenital nevi were also similar among white and Asian children. White children of European origin had a higher prevalence of sunburn freckles than the other ethnic groups. The prevalence among children of European descent was higher in subjects with light skin color, a propensity to burn rather than tan in the sun, a history of severe or frequent sunburn, freckling, and a high count of acquired melanocytic nevi. CONCLUSIONS: For most pigmented lesions prevalence rates were similar in the three ethnic groups examined. The results also suggest that the presence of large sunburn freckles in children of European descent correlates strongly with phenotypic risk factors that have been shown to be predictive of increased melanoma risk in adulthood. Parents should be counseled to take precautions with these children early in life in regard to overexposure to sunlight.
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21.) Melanotic macules following Blaschko's lines in McCune-Albright syndrome.
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SO - Br J Dermatol 1994 Feb;130(2):215-20
AU - Rieger E; Kofler R; Borkenstein M; Schwingshandl J; Soyer HP; Kerl H
PT - JOURNAL ARTICLE
AB - Hyperpigmented macules are a characteristic feature of neurofibromatosis and the McCune-Albright syndrome. Whereas neurofibromatosis 1 has an autosomal dominant mode of inheritance, it has been suggested that McCune-Albright syndrome is the result of a lethal gene surviving by mosaicism. Recent molecular studies have supported this concept by providing evidence of a somatic mutation of the gene encoding the G protein. We report two patients with McCune-Albright syndrome whose melanotic macules show a clear relation to the lines of Blaschko. The lines of Blaschko are thought to represent the dorso-ventral outgrowth of two different cell populations during embryogenesis, thus reflecting genetic mosaicism. A survey of published photographs of patients with McCune-Albright syndrome in the literature revealed additional cases with macules following Blaschko's lines. In other cases, the configuration of the macules was reminiscent of the flag-like rectangular pattern of pigmentation found in human chimaeras. A very early somatic mutation may have similar effects on the pigmentation pattern as a chimaeric state, which is the result of the double fertilization of an ovum. Cafe-au-lait spots in 10 of our own patients with neurofibromatosis 1 could not be associated with either Blaschko's lines or the rectangular pattern of pigmentation in chimaeras. We conclude that, in contrast with the cafe-au-lait spots in autosomal dominant neurofibromatosis 1, the configuration pattern of melanotic macules in McCune-Albright syndrome in many cases characteristically reflects the mosaic state of the organism.
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22.) Treatment of benign pigmented epidermal lesions by Q-switched ruby laser.
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SO - Int J Dermatol 1993 Dec;32(12):908-12
AU - Taylor CR; Anderson RR
PT - JOURNAL ARTICLE
AB - BACKGROUND. Disorders of cutaneous pigmentation are a common problem, which can cause substantial cosmetic morbidity. Traditional treatments are often ineffective and sometimes associated with further hyperpigmentation, hypopigmentation, or scarring. Because the Q-switched ruby laser has proven useful for the treatment of tattoos and, in a small number of cases, benign disorders of the epidermal melanin, we decided to apply this modality systematically to additional benign pigmented lesions. METHODS. Thirty-four benign pigmented epidermal lesions including lentigines, cafe-au-lait macules, and nevi spili in nine white patients were exposed to single pulses of a Q-switched ruby laser (694 nm, 40 ns pulse duration) at 4.5 and/or 7.5 J/cm2. RESULTS. After one treatment, substantial clearing occurred at each fluence in all lentigines and cafe-au-lait macules. Initial improvement was achieved in a small nevus spilus after two treatments at 4.5 J/cm2 and a larger nevus spilus after one treatment at 7.5 J/cm2 with complete removal of the junctional or compound nevi portion but no improvement in the cafe-au-lait portion. Complete return of the background pigment was observed by 1 year. There was no scarring. Immediately after treatment, histology revealed vacuolization of keratinocytes and melanocytes, and occasional subepidermal blisters. CONCLUSIONS. These findings show that while the Q-switched ruby laser may not be entirely useful for treating nevi spili, it does provide an effective treatment for lentigines and cafe-au-lait macules.
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23.) 510-nm pigmented lesion dye laser. Its characteristics and clinical uses.
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SO - J Dermatol Surg Oncol 1993 Apr;19(4):380-7
AU - Grekin RC; Shelton RM; Geisse JK; Frieden I
PT - JOURNAL ARTICLE
AB - BACKGROUND. Benign pigmented lesions are of a cosmetic concern to many individuals. Numerous treatments exist, including several types of lasers. The Candela 510 nm pigmented lesion dye laser has recently been added to this armamentarium. It is designed specifically for the treatment of superficial pigmented lesions while significantly decreasing the risk of scarring and prolonged hypopigmentation. OBJECTIVES. To describe the characteristics of the Candela pigmented lesion dye laser and report on the therapeutic outcome of patients treated for actinic lentigines, cafe-au-lait macules, melasma and red tattoos by one of the authors (RCG). METHODS. The Candela 510 nm pigmented lesion dye laser was used to treat solar lentigines, cafe-au-lait macules, melasma and red tattoo. RESULTS. Excellent outcomes resulted on facial and hand lentigines (89% and 88% of patients had greater than 75% clearing, respectively), but often required more than one treatment. Lentigines located on the upper extremities and trunk improved less dramatically. Immediate greying occurred universally. Bruising was often noted. Treatment failures have been observed especially in treating lentigines located on the lower extremities. Cafe-au-lait macules responded inconsistently, with facial lesions giving the best results. Melasma responded poorly, often with hyperpigmentation. Three red tattoos cleared. Treatment failure may be related to inaccurate clinical assessment of pigment depth or regrowth of the lesion. Several cases are presented to demonstrate clinical and histologic effects of the laser. CONCLUSION. The Candela 510-nm pigmented lesion dye laser is an effective treatment for superficial pigmented lesions. Its associated morbidity is minimal.
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24.) McCune-Albright syndrome: how many endocrinopathies can one patient have?
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SO - South Med J 1993 Mar;86(3):364-7
AU - Cavanah SF; Dons RF
PT - JOURNAL ARTICLE; REVIEW (15 references); REVIEW OF REPORTED CASES
AB - In this one patient with McCune-Albright syndrome are seen a multitude of endocrinopathies--more than in any case previously described. Only fibrous dysplasia with cafe-au-lait spots and/or endocrine hyperfunction are required for the diagnosis of the syndrome. Our patient has polyostotic fibrous dysplasia, cafe-au-lait spots, and at least four primary endocrinopathies. She had shown precocious puberty (with an ovarian follicular cyst later requiring resection), hyperthyroidism due to toxic nodular thyroid disease, primary hyperparathyroidism, and hyperprolactinemia (with associated hypogonadotropic hypogonadism and premature menopause). With this many organs involved in the same patient, it is hard to imagine that a genetic defect will not soon be identified as the unifying cause of the entire syndrome.
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25.) Aspects in neurofibromatosis from the viewpoint of dermatology.
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SO - J Dermatol 1992 Nov;19(11):868-72
AU - Niimura M
PT - JOURNAL ARTICLE
AB - The neurofibromatoses are a heterogenous set of conditions having clinical manifestations such as skin, nervous system, bone and eye disorders. The clinical pictures of the patients will obviously differ, and there is considerable variation of manifestations even within a family. During the last twenty-five years, one thousand and two hundred patients with neurofibromatosis were personally examined. Almost all our patients had classical von Recklinghausen disease. But in addition to these cases, there are 28 cases of NF-2 and 10 patients which we call multiple neurilemmomatosis. Also, there are related groups of patients with conditions which were not neurofibromatosis, such as 40 cases of localized multiple neurofibromas and 61 cases of localized cafe-au-lait spots. The features of neurofibromatosis in Japan are not different, compared with foreign countries, except increased pigmentation is more common. In addition to cafe-au-lait spots, some 20% of Japanese neurofibromatosis patients have pigmentary conditions which I termed hairy fuscoceruleus spots. These spots are blue-brown in colour, and one can see coarse hairs in them. Our recent study indicates that the patients with neurilemmomatosis have loss of heterozygosity of chromosome 22, the same position as the site of patients with NF-2. Neurilemmomatosis may be classified as an NF-2 without acoustic tumors.
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26.) [Unilateral lentiginosis--a segmental neurofibromatosis without neurofibromas]
[Die unilaterale Lentiginose--eine segmentale Neurofibromatose ohne Neurofibrome.]
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SO - Hautarzt 1992 Aug;43(8):491-5
AU - Gerhards G; Hamm H
PT - JOURNAL ARTICLE
AB - Segmental neurofibromatosis (NF) is a usually non-inherited form of NF that is characterized by unilateral neurofibromas and/or cafe-au-lait spots. In partial unilateral lentiginosis (PUL), apart from unilateral lentigines, cafe-au-lait spots of different dimensions have been described in some patients without fulfilling the diagnostic criteria for NF. We report on three patients representing the 4th to 6th cases of segmental NF without neurofibromas. The diagnosis resulted from unilateral cafe-au-lait spots of different sizes in all patients and axillary "freckling" and associated skeletal alterations in two patients each. As these findings are clinically and histologically comparable to reported cases of PUL and moreover fulfil the diagnostic criteria for segmental NF, our cases support the hypothesis that PUL is a segmental NF lacking neurofibromas.
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27.) Non-von Recklinghausen's neurofibromatosis presenting as hemifacial neurofibromas and contralateral cafe au lait spots.
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SO - J Am Acad Dermatol 1987 May;16(5 Pt 2):1090-6
AU - Wasserteil V; Bruce S; Riccardi VM
PT - JOURNAL ARTICLE
AB - The term neurofibromatosis designates a spectrum of disorders, the most common of which is von Recklinghausen's disease. We describe two patients with forms of neurofibromatosis other than von Recklinghausen's neurofibromatosis, characterized by involvement of half of the face and the contralateral lower extremity. Neither patient had a family history of neurofibromatosis, and a thorough evaluation of both patients failed to reveal evidence of von Recklinghausen's disease. The classification of neurofibromatosis is briefly summarized, with special emphasis placed on the need for a specific diagnosis regarding the type of neurofibromatosis for purposes of estimating prognosis and providing genetic counseling. The relationship between pregnancy and neurofibromatosis is also discussed.
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28.) The prevalence of cafe-au-lait patches in tuberous sclerosis.
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SO - Clin Exp Dermatol 1985 Nov;10(6):562-5
AU - Bell SD; MacDonald DM
PT - JOURNAL ARTICLE
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29.) Common and uncommon cutaneous findings in patients with ataxia-telangiectasia.
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SO - J Am Acad Dermatol 1984 Mar;10(3):431-8
AU - Cohen LE; Tanner DJ; Schaefer HG; Levis WR
PT - JOURNAL ARTICLE
AB - This series describes some common and uncommon cutaneous findings in twelve patients with ataxia-telangiectasia (A-T). All patients had the characteristic telangiectasia as described previously. However, the telangiectases did not conform to a classic photodistribution . Our series did include one patient with a pathologic reaction to light-simulating hydroa aestivale or vacciniforme . In addition, there were three patients with acanthosis nigricans in two unrelated families. Vitiligo, impetigo, recurrent herpetic gingivostomatitis, hirsutism, lipoatrophy, gray hair, progeroid changes and hyper- and hypopigmented macules were noted in our patients. Many of our patients had one or more caf'e au lait like-lesions in a dermatomal distribution. In addition, several of the family members showed one or more cafe au lait-like lesions, suggesting the possibility that this finding may represent a phenotypic expression in the skin of carriers of this cancer-prone syndrome.
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30.) [Diagnostic value of cafe-au-lait spots (author's transl)]
[Valeur diagnostique des taches cafe-au-lait (T.C.L.).]
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SO - Ann Dermatol Venereol 1980 Apr;107(4):313-27
AU - Ortonne JP; Brocard E; Floret D; Perrot H; Thivolet J
PT - JOURNAL ARTICLE; REVIEW (80 references)
AB - Clinical, histological and ultrastructural studies of cafe-au-lait spots (C. L. S.) are summarized, in order to establish a differential diagnosis between isolated C. L. S. and C. L. S. associated with polymalformative syndromes. The differential of C. L. S. include nevus spilus and Becker's melanosis. Distinctive clinical and histological features usually differentiate these entities. The incidence of C. L. S. in the general population is about 10 p. 100. It is significantly increased in neurofibromatosis (90 to 100 p. 100), Albright's syndrome (35 p. 100), ataxia telangiectasia (20 p. 100), Silver-Russel syndrome (45 p. 100), Watson's syndrome (60 p. 100), Leopard syndrome (38 p. 100) and Fanconi's anemia. An increased incidence of C. L. S. has been reported in tuberous sclerosis. C. L. S. have been observed in isolated patients with bony skeletal and muscular abnormalities, in Westerhof's syndrome, Leschke's syndrome, Cowden's disease, nevoid basal cell carcinoma syndrome, epidermal nevus syndrome, Gaucher's disease, Hunter's disease, Turner syndrome. Several clinical features of C. L. S. (number, size, distribution, family history) allow to distinguish isolated C. L. S. from C. L. S. associated with polymalformative syndromes. However, the distinction between "normal" and "abnormal" is not always clear cut. A study on the cellular and subcellular characterization of C. L. S. in a case of neurofibromatosis, tuberous sclerosis, Albright's syndrome and ataxia telangiectasia is reported. In each case, the number of epidermal melanocytes, the size of melanosomes and their mode of distribution within epidermal keratinocytes were evaluated. The authors emphasize that no specific histological or ultrastructural "marker" can be helpful for the differential diagnosis between the various forms of C. L. S. (C. L. S. of neurofibromatosis, Albright...).
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31.) The eastern Australian childhood nevus study: prevalence of atypical nevi, congenital nevus-like nevi, and other pigmented lesions.
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SO - J Am Acad Dermatol 1995 Jun;32(6):957-63
AU - Rivers JK; MacLennan R; Kelly JW; Lewis AE; Tate BJ; Harrison S; McCarthy WH
PT - JOURNAL ARTICLE
AB - BACKGROUND: Various melanocytic lesions are frequently observed. An understanding of phenotypic factors and environmental stimuli that are associated with these lesions may help explain their pathogenesis. OBJECTIVE: This study was undertaken to determine the prevalence of atypical nevi, blue nevi, cafe-au-lait macules, congenital nevus-like nevi, halo nevi, nevi spili, nevi 5 mm or more in diameter, and skin-colored melanocytic nevi in a population of schoolchildren and to explore risk factors including solar radiation in the development of these melanocytic lesions. METHODS: A cross-sectional study was performed by the same medical investigators to examine schoolchildren in three Australian cities that span a wide range of latitudes. RESULTS: Data from 1123 white Australian schoolchildren, 6 to 15 years of age, were analyzed. Acquired melanocytic nevi (atypical nevi, nevi or = 5 mm in diameter, and skin-colored nevi) were more likely to develop in older fair-skinned subjects who had freckles and lived closest to the equator. Cafe-au-lait macules and congenital nevus-like nevi were observed in 36.3% and 4.4% of the total population, respectively. Prevalence for both these types of melanocytic lesions increased significantly with decreasing latitude. Halo nevi were present in 5.3% of the subjects and were usually solitary. These lesions were related to the presence of atypical nevi primarily by virtue of their size rather than of other features of clinical atypia. CONCLUSION: Like melanocytic nevi in general, large and atypical nevi are strongly influenced by geographic location and, by implication, degree of solar radiation. The same can be said for congenital nevus-like nevi, which suggests that many so-called congenital nevi are in fact acquired early in life.
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32.) [Von Recklinghausen neurofibromatosis and dermal melanocytic nevi]
[Neurofibromatose von Recklinghausen und dermale melanozytare Navi.]
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SO - Hautarzt 1995 Apr;46(4):263-7
AU - Tanner M; Proksch E; Christophers E
PT - JOURNAL ARTICLE
AB - Neurofibromas, cafe au lait macules and freckles in the axillary or inguinal regions are common manifestations of von Recklinghausen's neurofibromatosis (NF-1). Less known is the simultaneous appearance of dermal melanocytic naevi. We describe the case of a 21-year-old Vietnamese woman who showed generalized, multiple neurofibromas, a solitary plexiform neurofibroma in the left gluteal region and Lisch nodules. In addition, there were several large grey-blue macules histologically characterized by fusiform pigment-bearing cells in the dermis, which we diagnosed as persistent aberrant mongolian spots. In the right zygomatic region she presented a grey-blue, hair-bearing macule, which we saw as a variant of Ota's naevus. A genetic background for this coincidence of a systemic with a local phakomatosis can be supposed, as both Schwann's cells and melanocytes are derived from the neural crest. Such pathologic rearrangement in the embryogenesis of the cellular elements could be important for the pathogenesis of NF-1 and dermal melanocytic nevi.
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33.) Fanconi anemia.
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SO - Dermatol Clin 1995 Jan;13(1):41-9
AU - Auerbach AD
PT - JOURNAL ARTICLE; REVIEW (49 references); REVIEW, TUTORIAL
AB - Fanconi anemia is a phenotypically and genotypically heterogeneous syndrome in which patients manifest various congenital abnormalities, bone marrow failure, and predisposition to malignancy. The primary dermatologic manifestations are pigmentation abnormalities (hyperpigmentation, hypopigmentation, cafe-au-lait spots) and cutaneous malignancies. The gene for one of the complementation groups (FACC) has been cloned, and the gene product has been shown to have a cytoplasmic localization, ruling out a direct role for the Fanconi anemia gene in DNA repair. A better understanding of the function of the FACC polypeptide, and the cloning of genes for the other Fanconi anemia complementation groups, should lead to a better understanding of the basic problems of birth defects and cancer predisposition and the interaction of genetic and epigenetic factors in the pathogenesis of these problems.
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34.) Treatment of epidermal pigmented lesions with the frequency-doubled Q-switched Nd:YAG laser. A controlled, single-impact, dose-response, multicenter trial.
====================================================================
SO - Arch Dermatol 1994 Dec;130(12):1515-9
AU - Kilmer SL; Wheeland RG; Goldberg DJ; Anderson RR
PT - CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; JOURNAL ARTICLE; MULTICENTER STUDY
AB - BACKGROUND AND DESIGN: The removal of benign, aesthetically important, pigmented lesions can be effectively treated with multiple modalities. Selective removal of the pigment by lasers is becoming increasingly popular. A three-center trial evaluated the effectiveness of the frequency-doubled Q-switched neodymium (Nd):YAG laser (532 nm, 2.0-mm spot size, 10 nanoseconds) in removing benign epidermal pigmented lesions with a single treatment. Forty-nine patients were treated for multiple lentigines (n = 37), for cafe au lait macules (n = 7), and for miscellaneous lesions (n = 5). Treatment areas were divided into four quadrants, irradiated with fluences of 2, 3, 4, or 5 J/cm2 and evaluated at 1- and 3-month intervals following treatment. RESULTS: For lentigines, response was related to dose with a greater than 75% pigment removal achieved in 60% of those lesions treated at higher energy fluences. Responses were more variable with other lesions, with fair-to-good improvement noted in most cases. Mild, transient erythema; hypopigmentation; and hyperpigmentation were noted in several patients, but resolved spontaneously within 3 months. No other textural changes, scarring, or other side effects were noted. CONCLUSION: The frequency-doubled Q-switched Nd: YAG laser (532 nm) safely and effectively treats benign epidermal pigmented lesions.
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35.) Agminated lentiginosis: case report and review of the literature.
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SO - Pediatr Dermatol 1994 Sep;11(3):241-5
AU - Micali G; Nasca MR; Innocenzi D; Lembo D
PT - JOURNAL ARTICLE; REVIEW (31 references); REVIEW, TUTORIAL
AB - Agminated lentiginosis (AL) is characterized by numerous lentigines confined to a body segment, with a sharp demarcation at the midline. So far, only 13 cases have been reported in the literature. We report a 30-year-old woman with a multifocal AL. The cutaneous lesions first appeared at 5 years of age and gradually increased in number with time. Clinically, they appeared as numerous brown macules, ranging in size from 1 to 5 mm in diameter, in a peppered distribution over an area extending bilaterally on the neck, chin, and cheeks. On the trunk the lesions were localized to the left shoulder and breast, involving the axilla and upper part of the abdomen down to the umbilicus. Four cafe au lait macules ranging in diameter from 10 to 15 mm were present, with no evidence of neurofibromas. Histopathology of a macule showed the features of lentigo; in addition, groupings of melanocytes were observed at the dermoepidermal junction. The differential diagnosis of AL includes speckled lentiginous nevus and segmental neurofibromatosis.
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36.) Cutaneous melanoma in a patient with neurofibromatosis: a case report and review of the literature.
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SO - Br J Dermatol 1994 Aug;131(2):290-4
AU - Duve S; Rakoski J
PT - JOURNAL ARTICLE; REVIEW (42 references); REVIEW OF REPORTED CASES
AB - We report the occurrence of a malignant melanoma in a patient with neurofibromatosis (von Recklinghausen's disease; NF 1). Neurofibromatosis, like malignant melanoma, is believed to be a disorder of neural crest origin, and is associated with a number of different malignancies, but a definite association between cutaneous malignant melanoma and neurofibromatosis has not been established. We describe a patient with a malignant melanoma and with neurofibromatosis, and review the literature pertinent to this topic. The malignant melanoma was not related to a cafe-au-lait patch or congenital naevus. The paucity of reports of patients with neurofibromatosis associated with cutaneous malignant melanoma suggests that these diseases probably do not occur together with any greater frequency than that determined by chance alone.
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37.) [Type 1 neurofibromatosis in Tunisia: 66 cases]
[Neurofibromatose type 1 en Tunisie: 66 cas.]
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SO - Ann Dermatol Venereol 1994;121(2):185-9
AU - Gouider R; Azaiz MI; Kchouk M; Lasram L; Ben Osman A; Mrabet A
PT - JOURNAL ARTICLE
AB - A multidisciplinary transversal descriptive study was conducted from June to October 1992 to determine the clinical manifestations and laboratory findings observed in 66 patients with type 1 neurofibromatosis. Diagnostic criteria were those of the National Institute of Health as recommended for subjects over 20 years of age. All patients over the age of 25 had cafe au lait spots, neurofibromas, lentigines and nodules. Occurrence of lesions of the central nervous system was significantly earlier than peripheral nervous manifestations. The optic glioma was the most frequent lesion of the central nervous system. Complications were observed during the first twenty years of the disease. Based on these findings, we propose a clinical and laboratory work-up designed as a function of age.
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38.) Bilateral pheochromocytoma-ganglioneuroma of the adrenal in type 1 neurofibromatosis.
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SO - Am J Surg Pathol 1993 Aug;17(8):837-41
AU - Chetty R; Duhig JD
PT - JOURNAL ARTICLE
AB - A 61-year-old woman with cafe-au-lait pigmentation and severe cutaneous neurofibromatosis type I was noted to have persistent hypertension after coronary artery bypass grafts. Clinical investigation revealed bilateral adrenal medullary tumors. The patient did not have a duodenal lesion or gastrointestinal symptoms. Histologic examination showed both tumors to be composed of typical pheochromocytoma with large areas of ganglioneuroma (compound or composite pheochromocytomas). The neuromatous foci contained areas of cystic degeneration and thick-walled vessels. The ganglion cells and neuromatous areas were negative for chromogranin, glial fibrillary acidic protein, synaptophysin and vasoactive intestinal peptide. The typical pheochromocytomatous areas were strongly immunopositive for chromogranin and synaptophysin. Bilateral classic pheochromocytomas are rare in type 1 neurofibromatosis, and we believe that bilateral composite pheochromocytomas are an extension of this association.
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39.) Laser treatment of benign pigmented epidermal lesions using a 300 nsecond pulse and 510 nm wavelength.
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SO - J Dermatol Surg Oncol 1993 Apr;19(4):341-7
AU - Fitzpatrick RE; Goldman MP; Ruiz-Esparza J
PT - JOURNAL ARTICLE
AB - Sixty-five patients having a total of 492 lesions were treated with the Candela pigmented lesion dye laser (510 nm, 300 ns). Lesions treated included cafe-au-lait macules, lentigines, seborrheic keratoses, and postinflammatory hyperpigmentation. Fluences varied from 2.0 J/cm2 to 3.5 J/cm2, but averaged 2.25 J/cm2. Response was good to excellent after one treatment with 40-50% completely clearing and an additional 33% clearing by 75% or more. Repeated treatments were capable of clearing residual lesions. Histologic examination revealed vacuolization of melanin-containing cells and suprabasilar vesicles. The only adverse sequelae were transient hypopigmentation and hyperpigmentation, which resolved in 4 to 6 months.
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40.) Segmental neurofibromatosis with only macular lesions.
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SO - Pediatr Dermatol 1993 Mar;10(1):43-5
AU - Micali G; Lembo D; Giustini S; Calvieri S
PT - JOURNAL ARTICLE
AB - A 16-year-old girl had a three-year history of many cafe au lait spots and freckles in a dermatomal distribution. The diagnosis of segmental neurofibromatosis (NF-5) was made on the basis of the clinical features, distribution of the lesions, and absence of systemic involvement. Only a few cases in the literature describe NF-5 with only macular lesions. An accurate clinical examination is important to identify this unusual presentation.
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41.) Preliminary experience with a flashlamp-pulsed tunable dye laser for treatment of benign pigmented lesions.
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SO - Cutis 1993 Mar;51(3):188-90
AU - Day TW; Pardue CC
PT - JOURNAL ARTICLE
AB - The principle of selective photothermolysis has been extended from the treatment of vascular to benign pigmented lesions. Cafe au lait birthmarks, solar lentigines, and ephelides can now be removed with a new pulsed-dye laser, with a low risk of scarring or hypopigmentation.
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42.) Unusual cutaneous manifestations of anhidrotic ectodermal dysplasia--a case report.
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SO - J Dermatol 1990 Jun;17(6):380-4
AU - Shah KC; Umrigar DD
PT - JOURNAL ARTICLE
AB - Congenital ectodermal dysplasia is a group of familial disorders that affect tissues and organs of ectodermal origin to varying degrees. Our patient with classical X-linked anhidrotic ectodermal dysplasia (AED) showed unusual skin manifestations including cafe-au-lait spots on the face, neck, buttock, and lumbo-sacral region; depigmentation of mucous membrane of the lower lip, buccal cavity, and left arm; absence of tragii; plantar keratoderma; and kyphosis of lower cervical and upper thoracic spines which have not been previously reported in the world literature.
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43.) Polyostotic fibrous dysplasia associated with extensive linear epidermal naevi.
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SO - Clin Exp Dermatol 1989 Sep;14(5):371-5
AU - Rustin MH; Bunker CB; Gilkes JJ; Robinson TW; Dowd PM
PT - JOURNAL ARTICLE
AB - Albright's syndrome is characterized by the combination of polyostotic fibrous dysplasia, precocious puberty and cafe-au-lait spots. We describe a patient with polyostotic fibrous dysplasia who also had extensive linear epidermal naevi, an association that has not been previously described in the English literature.
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44.) The diagnosis of neurofibromatosis-1 in the child under the age of 6 years.
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SO - Am J Dis Child 1989 Jun;143(6):717-9
AU - Obringer AC; Meadows AT; Zackai EH
PT - JOURNAL ARTICLE
AB - One-hundred sixty children under the age of 6 years presented for diagnostic evaluation regarding neurofibromatosis-1 (NF-1). Using the National Institutes of Health Consensus Conference criteria, 151 (94%) of the children were classified on initial examination: 112 were diagnosed as having NF-1 and 39 were found to be unaffected (all 39 have remained asymptomatic on follow-up). Nine could not be classified (3 have subsequently met minimal diagnostic criteria on follow-up). Clinical manifestations of NF-1 include cafe au lait spots (97%), freckling in the axillary or inguinal region (81%), Lisch nodules (30%), neurofibromas (15%), pseudoarthrosis (6%), and optic nerve gliomas (4%). More than minimal diagnostic criteria were met by 80% of the children who had a positive family history and by 32% of those who did not. Thus, the clinical diagnosis of NF-1 is possible in the child who is under 6 years of age, and the National Institutes of Health criteria are useful and applicable.
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45.) Effect of wavelength on cutaneous pigment using pulsed irradiation.
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SO - J Invest Dermatol 1989 May;92(5):717-20
AU - Sherwood KA; Murray S; Kurban AK; Tan OT
PT - JOURNAL ARTICLE
AB - Several reports have been published over the last two decades describing the successful removal of benign cutaneous pigmented lesions such as lentigines, cafe au lait macules' nevi, nevus of Ota, and lentigo maligna by a variety of lasers such as the excimer (351 nm), argon (488,514 nm), ruby (694 nm), Nd:YAG (1060 nm), and CO2 (10,600 nm). Laser treatment has been applied to lesions with a range of pigment depths from superficial lentigines in the epidermis to the nevus of Ota in the reticular dermis. Widely divergent laser parameters of wavelength, pulse duration, energy density, and spotsizes have been used, but the laser parameters used to treat this range of lesions have been arbitrary, with little effort focused on defining optimal laser parameters for removal of each type. In this study, miniature black pig skin was exposed to five wavelengths (504, 590, 694, 720, and 750 nm) covering the absorption spectrum of melanin. At each wavelength, a range of energy densities was examined. Skin biopsies taken from laser-exposed sites were examined histologically in an attempt to establish whether optimal laser parameters exist for destroying pigment cells in skin. Of the five wavelengths examined, 504 nm produced the most pigment specific injury; this specificity being maintained even at the highest energy density of 7.0 J/cm2. Thus, for the destruction of melanin-containing cells in the epidermal compartment, 504 nm wavelength appears optimal.
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46.) Pigmentary disorders in oriental skin.
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SO - Clin Dermatol 1989 Apr-Jun;7(2):11-27
AU - Jimbow M; Jimbow K
PT - JOURNAL ARTICLE; REVIEW (42 references); REVIEW, TUTORIAL
AB - Brown hyperpigmented disorders may be melanotic in which there is a normal number of epidermal melanocytes but melanin pigment is increased in the epidermis (eg, melasma), melanocytotic, in which melanocytes are increased (eg, cafe-au-lait macules), and nonmelanotic hyperpigmentation (eg, minocycline pigmentation). Blue hyperpigmented disorders may also be melanotic in which there is a normal number of epidermal melanocytes, but melanin pigment is present in the upper dermis (eg, gray/slate pigmentation in Riehl's melanosis), melanocytotic in which melanocytes are present in both the epidermis and dermis (eg, blue pigmentation in Nevus Ota and Mongolian spot), and nonmelanotic hyperpigmentation in which pigment is present in the deep dermis (eg, blue pigmentation in tattoos). Hypomelanosis (leukoderma) may be divided histopathologically into melanocytopenic disorders on which melanocytes are absent (eg, Vogt-Koyanagi-Harada syndrome and vitiligo), melanopenic disorders in which melanocytes are present but melanin is reduced (eg, nevus depigmentosus and incontinentia pigmenti achromians), and nonmelanotic disorders in which melanin pigmentation is unaffected (nevus anemicus) and the pigmentary abnormality is caused by something other than melanin. There are numerous pigmentary disorders in the oriental skin, and some of them are either characteristic to or established in the orientals. Importantly, a number of congenital hypermelanotic and hypomelanotic diseases (eg, nevus depigmentosus, incontinentia pigmenti, and incontinentia pigmenti achromians, take a distribution following to the Blaschko's line.
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47.) [Cutaneous signs of Noonan's syndrome. Apropos of a case with ulerythema ophyogenes, disseminated pilar and sudoral keratosis and progressive alopecia]
TT - [Les signes cutanes du syndrome de Noonan. A propos d'une observation avec ulerytheme ophryogene, keratose pilaire et sudorale disseminee et alopecie progressive.]
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SO - Ann Dermatol Venereol 1988;115(3):303-10
AU - Grob JJ; Laure M; Berge G; Taramasco M; Bore P; Benderitter T; Andrac L; Collet AM; Bonerandi JJ
PT - JOURNAL ARTICLE
AB - A case of typical Noonan syndrome (NS) with eye abnormalities, pterygium colli, cryptorchid testes, lymphoedema and asymmetrical cardiac septal hypertrophy is reported in a 8-month old infant. This case was particularly interesting since it included skin manifestations which enabled an early diagnosis to be made. Ulerythema ophryogenes has already been proposed as a cutaneous marker of NS, but the keratinization disorders in our patient also included disseminated keratosis of both hair follicles and sweat glands orifices. Abnormally brittle short curly hair has already been reported, but our patient exhibited progressive alopecia which is very rare in NS. Biochemical hair analysis did not show any abnormalities of aminoacids. All these features were suggestive of keratosis follicularis spinulosa decalvans. It therefore seems very likely that NS is associated with keratinization disorders but ulerythema ophryogenes might only be the limited form of these disorders. The other skin manifestations of NS are reviewed. Since the patient had 4 "cafe au lait" spots, the relation of NS with Von Recklinghausen syndrome, and neurofibromatosis-Noonan syndrome is discussed. Watson's Leopard and cardio-facial syndromes overlap with, and may represent subsets of NS.
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48.) Neurofibromatosis and Albright's syndrome.
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SO - Dermatol Clin 1987 Jan;5(1):193-203
AU - Riccardi VM
PT - JOURNAL ARTICLE; REVIEW (37 references)
AB - For both NF and Albright's syndrome, the pathogenetic relationships between the various elements of the respective syndromes remain a mystery, and the importance of nontumorous endocrine abnormalities in neurofibromatosis has, in my opinion, been overstated. Nonetheless, the parallel between the two disorders is striking, and the consistent occurrence of skin and skeletal dyplasias in both suggests that a search for the fundamental defect in either can be advanced by focusing on what is common to these two types of tissue. For example, how does one reconcile a disturbance of the melanosome with skeletal aberrations? An answer to that question will put us on the right track. One final question must be asked. Are neurofibromatosis and Albright's syndrome alternate manifestations of the same disorder? In a trivial sense, the answer may be yes. That is, in at least some instances, one condition may have been mistaken for the other, and thus a factitious overlap or "sameness" misconstrued. Upon closer scrutiny, however, there are two important points that would cast doubt on a positive response to this question: Neurofibromatosis, or at least neurofibromatosis I, is heritable as an autosomal dominant trait, whereas heritability has not been documented for Albright's syndrome; and I am unaware of reported cases that describe both disorders, diagnosed by criteria beyond cafe au lait spots and bone dysplasia, in one and the same individual, although such a case has been shared with me by S. A. Sorensen, M.D., of the Genetics Institute of Copenhagen, Denmark. The full reporting of such a case would be of great interest.
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49.) The Proteus syndrome: the Elephant Man diagnosed.
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SO - Br Med J (Clin Res Ed) 1986 Sep 13;293(6548):683-5
AU - Tibbles JA; Cohen MM Jr
PT - HISTORICAL ARTICLE; HISTORICAL BIOGRAPHY; JOURNAL ARTICLE
AB - Sir Frederick Treves first showed Joseph Merrick, the famous Elephant Man, to the Pathological Society of London in 1884. A diagnosis of neurofibromatosis was suggested in 1909 and was widely accepted. There is no evidence, however, of cafe au lait spots or histological proof of neurofibromas. It is also clear that Joseph Merrick's manifestations were much more bizarre than those commonly seen in neurofibromatosis. Evidence indicates that Merrick suffered from the Proteus syndrome and had the following features compatible with this diagnosis: macrocephaly; hyperostosis of the skull; hypertrophy of long bones; and thickened skin and subcutaneous tissues, particularly of the hands and feet, including plantar hyperplasia, lipomas, and other unspecified subcutaneous masses.
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50.) Juvenile xanthogranuloma: an analysis of 45 cases by clinical follow-up, light- and electron microscopy.
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SO - Acta Derm Venereol 1985;65(2):167-9
AU - Torok E; Daroczy J
PT - JOURNAL ARTICLE
AB - Juvenile xanthogranuloma is a benign, nevoid histiocytosis not related to histiocytosis X. The lesions wrinkle, then flatten out and in 40% of the cases they leave no trace without any treatment. It is more frequent in boys. One patient also had granulomatous lesions of the eye, 8 had cafe-au-lait spots and 3 epilepsy.
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51.) [Several cases of non-phlebologic pigmentation of the lower extremities]
[Quelques cas de pigmentations des membres inferieurs non ====================================================================
phlebologiques.]
SO - Phlebologie 1983 Oct-Dec;36(4):321-7
AU - Beurey J; Barthelme D; Eich D; Weber M
PT - JOURNAL ARTICLE
AB - Hyperpigmentation of the lower limbs does not always reflect a phlebological abnormality. The authors briefly recall other pathological circumstances which result in cutaneous hyperpigmentation : cutaneous porphyria (hyperpigmentation of the exposed parts), malignant melanoma, Recklinghausen's neurofibromatosis (cafe-au-lait spots and naevo-cellular naevi), pigmented dermatoses (lichen planus), fixed pigmented toxidermias, drug induced hyperpigmentations (minocyne, synthetic anti-malarials which can provoke the development of large areas of greyish coloured s in), reticular "hot water bottle" dermatitis and malingering syndromes.
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52.) Multiple agminated spindle cell nevi: unique clinical presentation and review.
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SO - J Am Acad Dermatol 1983 May;8(5):707-11
AU - Lancer HA; Muhlbauer JE; Sober AJ
PT - JOURNAL ARTICLE
AB - A boy with agminated spindle cell nevi is described. Present within the area of involvement were congenital nevocellular and composite spindle/nevocellular nevi. Other unusual features included a dynamic pattern of growth and regression of the lesions, with the presence of halo nevi and background cafe au lait pigmentation. This unique presentation of multiple nevi is discussed in the context of previous reports of agminated spindle cell nevi.
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53.) The invisible dermatoses.
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SO - J Am Acad Dermatol 1983 Apr;8(4):579-88
AU - Brownstein MH; Rabinowitz AD
PT - JOURNAL ARTICLE
AB - It is understandable that clinically normal skin may show abnormalities when examined with the light microscope, but paradoxical that biopsy of a clinically significant skin disorder may show a histologic picture that looks like normal skin. From the perspective of the dermatopathologist, the invisible dermatoses are clinically evident skin diseases that show a histologic picture resembling normal skin. A strategy for approaching the problem of the invisible dermatoses is to first examine the epidermis for fungi, cornoid lamellae (disseminated superficial actinic porokeratosis), and absence of the granular layer (dominant ichthyosis vulgaris). The cutis is then studied for hyalin deposition (macular amyloidosis), mast cells, microfilaria, dermal melanocytosis, silver granules, and absence of sweat glands (anhidrotic ectodermal dysplasia). Special stains may be required to uncover conditions like anetoderma and nevus elasticus. Comparison of the specimen with normal skin may disclose atrophoderma, lipoatrophy, vitiligo, or cafe au lait spot. Finally, technical problems should be considered, including sampling errors and mixup of specimens, either by the clinician or the laboratory.
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54.) Principles of genetics as related to the chromosome disorders and congenital malformations with reference to prenatal diagnosis and genetic counseling.
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SO - J Am Acad Dermatol 1981 Apr;4(4):379-94
AU - Alper JC
PT - JOURNAL ARTICLE; REVIEW (27 references)
AB - A basic discussion of the chromosome disorders and congenital malformations with specific reference to syndromes of interest to the dermatologist is presented. Although the chromosome disorders are uncommon, an introduction to the most prevalent clinical findings should enable the clinician to increase his/her index of suspicion as to the presence of one of these disorders. The latest chromosome banding technics and their application to clinical diagnosis are discussed. Congenital malformations are also uncommonly seen in the practice of dermatology. However, approximately 7% of all newborns have a cutaneous lesion at birth; some of these are of serious medical significance or the manifestation of a systemic disease. These include cafe au lait marks, congenital nevocellular nevi, and sebaceous nevi. A basic understanding of the mechanics and theory of prenatal diagnosis is becoming increasingly necessary for the dermatologist. Recently, epidermolytic hyperkeratosis has ben diagnosed antenatally, with the promise of other primary dermatologic disorders also being amenable to detection before birth. As the ability to detect and diagnose genetic disease becomes more refined, patients who are at risk themselves or whose offspring are at risk for these disorders will require more detailed information than ever before. Appropriate advice regarding recurrence risk, full spectrum of disease, availability of prenatal diagnosis, and any potential therapy will have to be proffered via genetic counseling.
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55.) Juvenile chronic granulocytic leukemia: emphasis on cutaneous manifestations and underlying neurofibromatosis.
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SO - Am J Dis Child 1980 Jul;134(7):654-8
AU - Mays JA; Neerhout RC; Bagby GC; Koler RD
PT - JOURNAL ARTICLE
AB - Five patients with juvenile chronic granulocytic leukemia are described. Two patients had multiple cafe-au-lait spots compatible with von Recklinghausen's neurofibromatosis, and three had cutaneous xanthomata. Recurrent cutaneous leukemic infiltrates were noted in two patients. The clinical course of all five patients was characterized by recurrent respiratory symptoms and pulmonary infiltrates that responded to antileukemic therapy in three. Chemotherapy controlled the symptoms but did not influence the eventually fatal outcome.
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56.) The removal of cutaneous pigmented lesions with the Q-switched ruby laser and the Q-switched neodymium: yttrium-aluminum-garnet laser. A comparative study.
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SO - J Dermatol Surg Oncol 1994 Dec;20(12):795-800
AU - Tse Y; Levine VJ; McClain SA; Ashinoff R
PT - JOURNAL ARTICLE
AB - BACKGROUND. The Q-switched ruby laser (QSRL) (694 nm) has been used successfully in the removal of tattoos and a variety of cutaneous pigmented lesions. The frequency-doubled Q-switched neodymium:yttrium-aluminum-garnet laser (QSNd:YAG) (1064 and 532 nm) has also been shown to be effective in the treatment of tattoos, however, little has been published regarding the QSNd:YAG laser in the removal of cutaneous pigmented lesions. OBJECTIVE. The purpose of this study is to compare the efficacy and side effect profile of the QSRL and the frequency-doubled QSNd:YAG lasers in the removal of cutaneous pigmented lesions, including lentigines, cafe-au-lait macules, nevus of Ota, nevus spilus, Becker's nevus, postinflammatory hyperpigmentation, and melasma. METHODS. Twenty patients with pigmented lesions were treated with the QSRL and the frequency-doubled QSNd:YAG lasers. Clinical lightening of the lesion was assessed 1 month after a single treatment. Side effects and patient satisfaction were also evaluated. RESULTS. A minimum of 30% lightening was achieved in all patients after only one treatment with either the QSRL or the frequency-doubled QSNd:YAG laser. The QSRL seems to provide a slightly better treatment response than the QSNd:YAG laser. Neither laser caused scarring or textural change of the skin. Most patients found the QSRL to be more painful during treatment, but the QSNd:YAG laser caused more postoperative discomfort. CONCLUSION. Both the QSRL and the frequency-doubled QSND:YAG laser are safe and effective methods of treatment of epidermal and dermal pigmented lesions.
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57.) [Smooth muscle hamartoma: anatomoclinical characteristics and nosological limits]
[Hamartome musculaire lisse: caracteres anatomo-cliniques et limites nosologiques.]
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SO - Ann Dermatol Venereol 1993;120(12):879-83
AU - de la Espriella J; Grossin M; Marinho E; Belaich S
PT - JOURNAL ARTICLE; REVIEW (37 references); REVIEW, TUTORIAL
AB - Smooth muscle hamartoma is an uncommon cutaneous dysembryoplasia usually diagnosed in infancy. Among the 61 cases published since 1923, 56 were congenital and 3 appeared in young adults. We report a case in which the lesions started at the age of 15 years as a papular plaque in the right mammary region of a young woman. A review of the literature showed that the usual clinical presentation is a frequently pigmented plaque made of often follicular papules and measuring 1 to 10 centimeters on average. Excessive hairiness is the most frequent sign, being observed in more than two-thirds of the cases, and Darier's pseudo-sign is present in about 53 p. 100 of the patients. The disease is electively located on the lumbar region, the back and the root of the limbs. In 3 cases the lesions were generalized and the patients looked like fatty "Michelin-Tire Babies". The course of the disease is always favourable, and associated pathologies remain exceptional: urticaria pigmentosa and psychomotor retardation have been reported in two cases of the generalized form. Histology is characterized by the presence of numerous smooth muscle fibres disseminated in the dermis and diversely oriented, sometimes in contact with hair follicles which retain their normal morphology. The differential clinical diagnosis is with naevocytic naevus, cafe-au-lait spots, mastocytosis and connective tissue hamartoma. Belatedly revealed forms of the disease must be distinguished from Becker's hamartoma, but it must be known that in certain cases the classification is so difficult that some authors have suggested that smooth muscle hamartoma and Becker's hamartoma are only two poles of a single spectrum of dysembryoplastic lesions involving to varying degrees the epidermic and hair structures. Finally, the distinction between the localized forms of late onset smooth muscle hamartoma and multiple leiomyomas "en plaques" remains difficult both anatomico-clinically and nosologically
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58.) Multiple café au lait spots in familial patients with MAP2K2 mutation.
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Takenouchi T1, Shimizu A, Torii C, Kosaki R, Takahashi T, Saya H, Kosaki K.
Author information
1
Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
Abstract
Recent advances in genetic diagnostic technologies have made the classic disease nosology highly complicated. This situation is exemplified by rasopathies, among which neurofibromatosis type 1 and Noonan syndrome represent prototypic entities. The former condition is characterized by multiple café au lait spots and neurofibromas, while the latter is characterized by distinct facial features, webbed neck, congenital heart disease, and a short stature. On rare occasions, the features of both neurofibromatosis and Noonan syndrome co-exist within an individual; such patients are diagnosed as having neurofibromatosis-Noonan syndrome. Here, we report familial patients with multiple café au lait spots and Noonan syndrome-like facial features. A mutation analysis unexpectedly revealed a mutation in MAP2K2 in both the propositus and his mother. The propositus fulfilled the diagnostic criteria for neurofibromatosis type 1, but his mother did not. Their phenotype was not consistent with that of cardio-facio-cutaneous syndrome, which is classically known to be associated with MAP2K2 mutations. The mother of the propositus had cervical cancer at the age of 23 years, consistent with the oncogenic tendency associated with rasopathies. The phenotypic combination of multiple café au lait spots and Noonan syndrome-like facial features suggested a diagnosis of neurofibromatosis-Noonan syndrome. Whether this condition represents a discrete disease entity or a variable expression of neurofibromatosis type 1 has long been debated. The present observation suggests that some perturbation in the RAS/MAPK signaling cascade results in multiple café au lait spots, a key diagnostic phenotype of rasopathies, although the exact mechanism remains to be elucidated.
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59.) A severe form of Noonan syndrome and autosomal dominant café-au-lait spots - evidence for different genetic origins.
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Acta Paediatr. 2009 Apr;98(4):693-8. doi: 10.1111/j.1651-2227.2008.01170.x. Epub 2008 Dec 18.
Nyström AM1, Ekvall S, Strömberg B, Holmström G, Thuresson AC, Annerén G, Bondeson ML.
Author information
1
Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Abstract
AIM:
The clinical overlap among Noonan syndrome (NS), cardio-facio-cutaneous (CFC), LEOPARD and Costello syndromes as well as Neurofibromatosis type 1 is extensive, which complicates the process of diagnosis. Further genotype-phenotype correlations are required to facilitate future diagnosis of these patients. Therefore, investigations of the genetic cause of a severe phenotype in a patient with NS and the presence of multiple café-au-lait spots (CAL) spots in the patient and four members of the family were performed.
METHODS:
Mutation analyses of candidate genes, PTPN11, NF1, SPRED1 and SPRED2, associated with these syndromes, were conducted using DNA sequencing.
RESULTS:
A previously identified de novo mutation, PTPN11 F285L and an inherited NF1 R1809C substitution in the index patient were found. However, neither PTPN11 F285L, NF1 R1809C, SPRED1 nor SPRED2 segregated with CAL spots in the family. The results indicate that the familial CAL spots trait in this family is caused by a mutation in another gene, distinct from previous genes associated with CAL spots in these syndromes.
CONCLUSION:
We suggest that the atypical severe symptoms in the index patient may be caused by an additive effect on the F285L mutation in PTPN11 by another mutation, for example the NF1 R1809C or alternatively, the not yet identified gene mutation associated with CAL spots in this family.
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60.) The diagnostic and clinical significance of café-au-lait macules.
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Pediatr Clin North Am. 2010 Oct;57(5):1131-53. doi: 10.1016/j.pcl.2010.07.002.
Shah KN1.
Author information
1
Department of Pediatrics and Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. shahk@email.chop.edu
Abstract
Café-au-lait, also referred to as café-au-lait spots or café-au-lait macules, present as well-circumscribed, evenly pigmented macules and patches that range in size from 1 to 2 mm to greater than 20 cm in greatest diameter. Café-au-lait are common in children. Although most café-au-lait present as 1 or 2 spots in an otherwise healthy child, the presence of multiple café-au-lait, large segmental café-au-lait, associated facial dysmorphism, other cutaneous anomalies, or unusual findings on physical examination should suggest the possibility of an associated syndrome. While neurofibromatosis type 1 is the most common syndrome seen in children with multiple café-au-lait, other syndromes associated with one or more café-au-lait include McCune-Albright syndrome, Legius syndrome, Noonan syndrome and other neuro-cardio-facialcutaneous syndromes, ring chromosome syndromes, and constitutional mismatch repair deficiency syndrome.
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61.) A girl with cutaneous hyperpigmentation, café au lait spots and ring chromosome 15 without significant deletion.
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Genet Couns. 2003;14(3):337-42.
Morava E1, Bartsch O, Czako M, Frensel A, Kárteszi J, Kosztolányi GY.
Author information
1
University of Pécs, Medical Faculty, Department of Medical Genetics and Child Development, Pécs, 7623 Hungary. emorava@yahoo.com
Abstract
Ring chromosome 15 [r(15)] syndrome is characterised by specific facial features, café au lait spots, failure to thrive, mental retardation and typically with a terminal deletion of the long arm of chromosome 15. We report a 2.5 year old girl showing normal growth and development, large hyperpigmented skin changes showing hypopigmentated areas inside, multiple café au lait spots and premature graying-like hypopigmentation of scalp hair. She had a karyotype of r(15) in peripheral lymphocytes and fibroblasts. By FISH analysis the breakpoint was located distal to locus D15S936 (15q26.3) and within 300 kb of the end of the chromosome, indicating no deletion of functional genes on 15q. Hyperpigmentation and café au lait spots are rare signs in ring chromosome syndromes, but with r(15) syndrome, café au lait spots have been described in about 30% of patients and have been considered to result from the deletion of gene(s) on distal 15q. Based on the frequent observation of patchy hyperpigmentation with the r(15) syndrome, absent hyperpigmentation in cases of distal 15q deletion without a ring chromosome, and the telomeric breakpoint location in our patient indicating no significant deletion, we propose that the cutaneous hyperpigmentation and café au lait spots in our proband represent effects of the r(15) chromosome but are not caused by the deletion of specific gene(s) on distal 15q. Patchy skin hypopigmentation is a well known nonspecific sign in cytogenetic mosaicism which is commonly seen in ring syndrome.
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62.) Diagnostic outcome in children with multiple café au lait spots.
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Pediatrics. 1992 Dec;90(6):924-7.
Korf BR1.
Author information
1
Division of Genetics, Children's Hospital, Boston, MA 02115.
Abstract
Forty-one children, ranging in age from 1 month to 14 years, had six or more café au lait spots at their initial visit and were examined annually. Signs of neurofibromatosis type 1 eventually developed in 24. The most common feature to appear to confirm the diagnosis was skin-fold freckling, which occurred in 18 subjects. Diagnosis was based on the appearance of Lisch nodules in 5, and on neurofibromas in 3. In most instances, diagnosis was established within 3 years of initial evaluation, usually before 5 years of age. Six children had a segmental distribution of café au lait spots, suggesting segmental neurofibromatosis. In 3, diagnoses other than neurofibromatosis type 1 were established (Bannayan-Riley-Rulvalcaba syndrome, multiple lentigines syndrome, and fibrous dysplasia). In 8 subjects only multiple café au lait spots are present, and no definite diagnosis has been established. It is concluded that with regular follow-up, including physical and ophthalmological examinations, a definite diagnosis, most commonly neurofibromatosis type 1, can be established for most children having multiple café au lait spots.
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63.) Café au lait macules and juvénile polyps.
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Pediatr Dermatol. 2007 May-Jun;24(3):E17-21.
Pacheco TR1, Scatena LS, Hoffenberg EJ, Gralla J, Lee LA.
Author information
1
Department of Dermatology, University of Colorado at Denver and the Health Sciences Center, Aurora,Colorado, USA. theresa.pacheco@uchsc.edu
Abstract
Several hereditary and nonhereditary gastrointestinal tract polyposis syndromes exhibit extra-intestinal manifestations, including cutaneous findings. However, a lack of information exists regarding cutaneous features of juvenile polyposis. Our objective was to document the prevalence of cutaneous hyperpigmented lesions in children with juvenile polyposis coli or juvenile polyposis coli and their first degree relatives.Children seen in the gastroenterology practice at The Children's Hospital in Denver, Colorado with polyps (juvenile polyposis coli, sporadic juvenile polyps, and familial adenomatous polyposis coli) and their first degree relatives were invited to participate in the study. A comprehensive skin examination was performed on those who consented to participate. We found that 8 of 14 patients (eight with juvenile polyposis coli, four with juvenile polyposis, and two with familial adenomatous polyposis coli) had at least one café-au-lait macule, compared with three of 27 relatives (p=0.003).The prevalence of at least one café-au-lait macule in our patients (8/14 or 57.1%, CI: 28.9–82.3%) was significantly higher than the general population prevalence of 28.5% (p=0.023). However, if the two patients with familial adenomatous polyposis coli were excluded, the comparison with the general population prevalence did not reach statistical significance (p=0.095). The prevalence of multiple cafe´-au-lait macules in our patients (4/14 or 28.6%; CI:8.4–58.1%) was significantly higher than the general population prevalence of 5.2% (p ¼ 0.005). A notable finding was the presence of multiple café -au-lait macules in 4 of 12 juvenile polyposis coli/juvenile polyposis patients.Two patients with juvenile polyposis coli also had lentigines. In this selected case series, we observed single or multiple café-au-lait macules in a high proportion of children with the three types of polyps. Further studies are needed to assess a possible common pathway for hamartomatous polypsand café-au-lait macules.
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64.) Café-au-lait spots in neurofibromatosis type 1 and in healthy control individuals: hyperpigmentation of a different kind?
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Arch Dermatol Res. 2006 Apr;297(10):439-49. Epub 2006 Feb 15.
De Schepper S1, Boucneau J, Vander Haeghen Y, Messiaen L, Naeyaert JM, Lambert J.
Author information
1
Department of Dermatology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium.
Abstract
Solitary café-au-lait spots are quite common in the general population but multiple café-au-lait macules (CALM) are often indicative of an underlying genetic disorder. The frequency of having more than five CALM is rare in normal individuals and is therefore considered as a cut-off for the diagnosis of neurofibromatosis type 1 (NF1). The etiopathogenesis of these macules is still very obscure. In this study we compared epidermal melanocyte and dermal mast cell numbers between four groups: control normal and control CALM skin, and NF1 normal and NF1 CALM skin and elaborated a possible role for stem cell factor (SCF) in CALM formation. The groups were analyzed by immunohistochemistry for numerical analysis of the melanocyte and mast cell population and by ELISA, western blot analysis and real-time quantitative PCR for further determination of the role of SCF. We found a significant increase in melanocyte density in NF1 CALM skin compared with the isolated CALM in control individuals. However, both groups displayed a similar increase in mast cell density. In addition, we found increased levels of soluble SCF in NF1 CALM and in NF1 normal fibroblast supernatant. We conclude that SCF is an important cytokine in NF1 skin, but that additional (growth) factors and/or genetic mechanisms are needed to induce NF1-specific CALM hyperpigmentation.
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65.) Cafe au lait has hue of its own.
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Dermatol Online J. 2003 Dec;9(5):8.
Orion E1, Matz H, Wolf D, Wolf R.
Author information
1
Dermatology Unit, Kaplan Medical Center, Rechovot, Israel.
Abstract
Segmental pigmentation disorder is a pigmentation disorder (hypo- or hyperpigmentation) first described some 20 years ago. It appears early in life, is segmental, and usually has a sharp border in the midline. It can be confused clinically and histologically with several pigmentary disorders, especially with giant or segmental cafe-au-lait macules. The purpose of this article is to promote, revive, and refresh this somewhat neglected entity, and to further subdivide it into two types: segmental pigmentation disorder simplex and segmental cafe-au-lait. We illustrate our contention with case reports.
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66.) Predictive value of café au lait macules at initial consultation in the diagnosis of neurofibromatosis type 1.
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Arch Dermatol. 2009 Aug;145(8):883-7. doi: 10.1001/archdermatol.2009.169.
Nunley KS1, Gao F, Albers AC, Bayliss SJ, Gutmann DH.
Author information
1
Department of Dermatology, Washington University School of Medicine, St Louis, MO 63110, USA.
Abstract
OBJECTIVE:
To evaluate the predictive utility of the number and morphologic appearance of isolated café au lait macules (CALMs) in establishing the diagnosis of neurofibromatosis type 1 (NF1) in a cohort of children referred to an NF1 subspecialty clinic.
DESIGN:
Retrospective study of patients seen between the years 2004 and 2007.
SETTING:
Tertiary care neurofibromatosis referral clinic at St Louis Children's Hospital. Patients The study population comprised 110 patients who presented with CALMs and no other diagnostic features of NF1. The median number of CALMs at initial presentation was 6, while the median age of the patients was 33 months. The median age at the last follow-up examination was 76.5 months.
MAIN OUTCOME MEASURES:
Number and morphologic appearance of CALMs and diagnosis of NF1.
RESULTS:
Thirty-four of the children met diagnostic criteria for NF1 during the study period. Thirty-two children met criteria prior to age 72 months, and 2 children met criteria after 72 months. The mean number of CALMs at presentation in children eventually diagnosed as having NF1 (11.8 CALMs) was significantly higher than the mean number of CALMs in children not diagnosed as having NF1 (4.6 CALMs). Of the 44 children who had 6 or more typical CALMs at presentation, 34 children met criteria for NF1. Sixty-eight patients had CALMs described as "typical," while 42 patients had "atypical" CALMs. Only 2 patients with atypical CALMs met criteria for NF1. Conclusion The majority of patients with 6 or more CALMs will eventually meet diagnostic criteria for NF1, typically by age 6 years, and this likelihood increases with increasing number and typical morphologic appearance of CALMs.
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67.) Nevoid basal cell carcinoma syndrome presenting with neck pits and café au lait patches.
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J Clin Pediatr Dent. 2010 Fall;35(1):95-100.
Balasundram S1, Kovilpillai FJ, Hopper C.
Author information
1
Eastman Dental Institute, University College London, London, United Kingdom. satbala@yahoo.com
Abstract
BACKGROUND:
A 10- year-old patient presented with a slow growing jaw swelling. The initial general examination did not reveal any significant findings.
METHODS:
Conservative enucleation of the cyst confirmed it to be an odontogenic keratocyst. The patient remained asymptomatic for the following 2 years and subsequently presented cystic lesions in jaws with displaced teeth. These cysts were enucleated and were confirmed to be odontogenic keratocysts . The patient has been on regular follow up since then and subsequent scans have shown further occurrence of cysts in the jaws with displacement of the third molars.
RESULTS:
Clinical examination also revealed macrocephaly, fronto-parietal bossing, pitting on palmar and plantar surfaces, calcification of falx cerebri and splayed ribs, confirming the diagnosis of nevoid basal cell carcinoma syndrome. He also presented with a cafi au lait patch and skin pits on the neck. The family history was negative for features of nevoid basal cell carcinoma syndrome.
CONCLUSION:
Nevoid basal cell carcinoma syndrome is a condition that can cause significant morbidity if not detected early. Over the years this syndrome has presented with many other non specific phenotype presentation, of which the current finding may be one of This calls for meticulous assessment and examination of patients and a standardized protocol in screening and managing these patients that may facilitate a more beneficial outcome for the patient.
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68.) Divided café-au-lait macule of the mouth.
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J Am Acad Dermatol. 2007 May;56(5 Suppl):S98-9.
Sergay A1, Silverberg NB.
Author information
1
Department of Dermatology, St Luke's-Roosevelt Hospital Center, New York, New York 10025, USA.
Abstract
We describe a 4-year-old, otherwise healthy boy with a congenital history of a perioral and labial segmental café-au-lait macule, who was noted to have unilateral localized gingival hyperpigmentation that aligned with the café-au-lait macule. This case is highly illustrative of the embryologic timing of the genetic event locally, which leads to café-au-lait type hyperpigmentation. Because the facial features and the ectoderm overlying the facial muscles develop around the third to fourth week of gestation, the distribution of this café-au-lait macule suggests development at the same time.
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69.) Molecular screening strategies for NF1-like syndromes with café-au-lait macules (Review).
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Mol Med Rep. 2016 Nov;14(5):4023-4029. doi: 10.3892/mmr.2016.5760. Epub 2016 Sep 22.
Zhang J1, Li M1, Yao Z1.
Author information
1
Department of Dermatology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
Abstract
Multiple café-au-lait macules (CALM) are usually associated with neurofibromatosis type 1 (NF1), one of the most common hereditary disorders. However, a group of genetic disorders presenting with CALM have mutations that are involved in human skin pigmentation regulation signaling pathways, including KIT ligand/KIT proto‑oncogene receptor tyrosine kinase and Ras/mitogen‑activated protein kinase. These disorders, which include Legius syndrome, Noonan syndrome with multiple lentigines or LEOPARD syndrome, and familial progressive hyperpigmentation) are difficult to distinguish from NF1 at early stages, using skin appearance alone. Furthermore, certain syndromes are clinically overlapping and molecular testing is a vital diagnostic method. The present review aims to provide an overview of these 'NF1‑like' inherited diseases and recommend a cost‑effective strategy for making a clear diagnosis among these diseases with an ambiguous borderline.
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70.) The first Slovak Legius syndrome patient carrying the SPRED1 gene mutation.
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Gen Physiol Biophys. 2017 Feb 2. doi: 10.4149/gpb_2016032. [Epub ahead of print]
Sekelska M1, Briatkova L, Olcak T, Bolcekova A, Ilencikova D, Kadasi L, Zatkova A.
Author information
1
Department of Molecular Biology, Comenius University, Faculty of Natural Sciences, Mlynska dolina, Ilkovicova 6, 842 15 Bratislava, Slovakia.
Abstract
Autosomal dominant disorder Legius syndrome (NF1- like syndrome) shows phenotype features that overlap with neurofibromatosis type 1 (NF1), such as CALMs, freckling, macrocephaly and learning disability. Mutation analysis provides an important tool in order to distinguish two entities that have different clinical implications. We analyzed SPRED1 gene by cDNA and/or gDNA sequencing in a cohort of 46 Slovak patients in whom previously NF1 mutation was excluded. In one case we identified a nonsense mutation c.46C>T (p.Arg16*) in exon 2 of SPRED1 gene, confirming diagnosis of Legius syndrome. This mutation was reported previously.
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