Generalized vitiligo is an autoimmune disorder characterized by acquired white patches of skin and overlying hair, the result of loss of melanocytes from involved areas. The most common disorder of pigmentation, vitiligo occurs with a frequency of 0.1-2.0% in various populations. Family clustering of cases is not uncommon, in a non-Mendelian pattern suggestive of multifactorial, polygenic inheritance. We surveyed 2624 vitiligo probands from North America and the UK regarding clinical characteristics, familial involvement, and association with other autoimmune disorders, the largest such survey ever performed. More than 83% of probands were Caucasians, and the frequency of vitiligo appeared approximately equal in males and females. The frequency of vitiligo in probands' siblings was 6.1%, about 18 times the population frequency, suggesting a major genetic component in disease pathogenesis. Nevertheless, the concordance of vitiligo in monozygotic twins was only 23%, indicating that a non-genetic component also plays an important role. Probands with earlier disease onset tended to have more relatives affected with vitiligo, suggesting a greater genetic component in early onset families. The frequencies of six autoimmune disorders were significantly elevated in vitiligo probands and their first-degree relatives: vitiligo itself, autoimmune thyroid disease (particularly hypothyroidism), pernicious anaemia, Addison's disease, systemic lupus erythematosus, and probably inflammatory bowel disease. These associations indicate that vitiligo shares common genetic aetiologic links with these other autoimmune disorders. These results suggest that genomic analysis of families with generalized vitiligo and this specific constellation of associated autoimmune disorders will be important to identify the mechanisms of genetic susceptibility to autoimmunity.

Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families.

Hemangiomas are the most common soft-tissue tumors of infancy, occurring in approximately 5 to 10 percent of one-year-old children. Despite the frequency of these tumors, their pathogenesis is not completely understood, and the best approach to their management remains controversial. Research on angiogenesis, an improved knowledge of the classification of the vascular anomalies of infancy, advances in imaging techniques, recently identified complications, and new therapeutic approaches, such as treatment with interferon and lasers, have altered our understanding of this common childhood problem and the way we approach it. The term hemangioma has traditionally been applied to a variety of vascular . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199907153410307

Hemangiomas in Children

Aplasia cutis congenita is a condition in which localized or widespread areas of skin are absent at birth. Several distinct clinical subtypes occur, characterized by the location and pattern of skin absence, the presence of associated malformations, and the mode of inheritance. The disorder is seen most frequently on the scalp, often as a solitary lesion without other anomalies. Scalp lesions can be seen in association with limb reduction defects and in association with epidermal and organoid nevi. Lesions may overlie overt or occult embryologic malformations. A form of aplasia cutis congenita occurs in association with placental infarcts or the in utero death of a twin fetus. The condition may be associated with epidermolysis bullosa, specific teratogens or intrauterine infections, or it may occur in the presence of chromosomal abnormalities, ectodermal dysplasias, or other syndromes of malformation. A classification for aplasia cutis congenita is proposed.

Aplasia cutis congenita: A clinical review and proposal for classification

Summary

Background The risk of malignant melanoma in congenital melanocytic naevi (CMN) is a matter of controversial and ongoing debate.



Objectives  The purpose of this systematic review is to provide a careful and detailed summary of the published data, including several recently published studies.



Methods  Articles on CMN (n = 1424) were retrieved from Medline, 1966–October 2005. Case reports and studies lacking relevant clinical information were excluded. Only systematic collections of cases were taken into consideration. Series with fewer than 20 patients or studies with a mean follow-up of <3 years were regarded as epidemiologically less significant.



Results  Fourteen articles were finally chosen for further analysis. The studies varied significantly with respect to study design (source of cases; retrospective vs. prospective analysis), age of patients, follow-up time, and naevus characteristics. The frequency of melanomas ranged between 0·05% and 10·7% and was significantly higher in smaller studies (P < 0·0001). In a total of 6571 patients with CMN who were followed for a mean of 3·4–23·7 years, 46 patients (0·7%) developed 49 melanomas. The mean age at diagnosis of melanoma was 15·5 years (median 7). By comparison with age-adjusted data from the Surveillance, Epidemiology and End Results database, we calculated that patients with CMN carry an approximately 465-fold increased relative risk of developing melanoma during childhood and adolescence. Primary melanomas arose inside the naevi in 33 of 49 cases (67%). In seven cases (14%), metastatic melanoma with unknown primary was encountered; in four cases (8%) the melanoma developed at an extracutaneous site. The risk of developing melanoma and the rate of fatal courses were by far highest in CMN ≥40 cm in diameter.



Conclusions  The overall risk of melanoma of 0·7% in all 14 studies was lower than expected. The higher incidence of melanomas in smaller studies indicates selection bias. The melanoma risk strongly depends on the size of CMN and is highest in those naevi traditionally designated as garment naevi. The median age of 7 years at diagnosis of melanoma points to a risk maximum in childhood and adolescence. Future studies on CMN should report: (i) diameter, percentage of body surface, and localization of the CMN; (ii) percentage of naevus area removed by excision or subject to dermabrasion or other superficial treatments; (iii) mean and median age at entry into the study; (iv) mean and median follow-up time; (v) details on each melanoma case; (vi) standardized morbidity ratio of melanoma; and (vii) percentage of neurocutaneous melanosis.

https://www.naevus-netzwerk.de/wp-content/uploads/Krengel_2006.pdf

Melanoma risk in congenital melanocytic naevi: a systematic review.

Listeriosis during pregnancy: a case series and review of 222 cases.

Giant pigmented nevi: clinical, histopathologic, and therapeutic considerations.

We conducted a 20-year prospective review of 41 pediatric patients with a diagnosis of hypomelanosis of Ito. No evidence pointed to hereditary transmission of the disease. Associated extracutaneous pathology was mainly of the nervous and musculoskeletal systems. Three of 19 patients had chromosomal anomalies. Hypomelanosis of Ito is a clinically well-characterized syndrome in which chromosomal instability may be a component. Criteria for its presumptive and definitive diagnosis are proposed.

Hypomelanosis of Ito: Diagnostic Criteria and Report of 41 Cases

Background: Because of their size and the possibility of complications, giant hemangiomas represent a therapeutic challenge Various forms of treatment have been used, with variable results, including surgery, embolization, lasers, pentoxifylline, and corticosteroids Interferon alfa has been used successfully to treat life-threatening hemangiomas, possibly by means of its antiangiogengenic activity Observations: We treated 7 infants with organ-interfering and/or life-threatening giant hemangiomas with subcutaneous injections of 3 million U/m 2 per day of interferon alfa-2b during the first month and subsequently every 48 to 72 hours, depending on the evolution in each case The treatment lasted from 3 to 12 months In 2 patients, interferon alfa-2b was administered while prednisone therapy was being tapered In all 7 patients, there was considerable reduction of the volume of the hemangiomas and remission of their complications All patients presented with fever, neutropenia, and an increase in serum aminotransferase levels The patients who received interferon alfa-2b and prednisone seemed to improve at a faster rate Conclusions: Interferon alfa-2b is a good option for the treatment of patients with steroid-resistant, organ-interfering and/or life-threatening giant hemangiomas In our experience, the adverse effects were transient and minor and did not require the interruption of the treatment Arch Dermatol 1997;133:1567-1571

Therapeutic efficacy of interferon alfa-2b in infants with life-threatening giant hemangiomas.

Background Silvery hair and severe dysfunction of the central nervous system (neuroectodermal melanolysosomal disease or Elejalde syndrome) characterize this rare autosomal recessive disease. Main clinical features include silver-leaden hair, bronze skin after sun exposure, and neurologic involvement (seizures, severe hypotonia, and mental retardation). Large granules of melanin unevenly distributed in the hair shaft are observed. Abnormal melanocytes and melanosomes and abnormal inclusion bodies in fibroblasts may be present. Differential diagnosis with Chediak-Higashi syndrome and Griscelli syndrome must be done. Observations We studied pediatric patients with silvery hair and profound neurologic dysfunction. Immune impairment was absent. Age of onset of neurologic signs ranged from 1 month to 11 years; the signs included severe muscular hypotonia, ocular alterations, and seizures. Mental retardation since the first months of life was noted in 4 cases. Psychomotor development was normal in 3 cases, but suddenly the patients presented with a regressive neurologic process. Four patients died between 6 months and 3 years after the onset of neurologic dysfunction. One patient showed characteristic ultrastructural findings of Elejalde syndrome. Conclusions Elejalde syndrome is different from Chediak-Higashi and Griscelli syndrome and is characterized by silvery hair and frequent occurrence of fatal neurologic alterations. Psychomotor impairment may have 2 forms of presentation: congenital or infantile. Although Elejalde syndrome and Griscelli syndrome are similar, the possibility that they are 2 different diseases, although probably allelic related, is suggested.

https://jamanetwork.com/journals/jamadermatology/articlepdf/477721/dob8029.pdf

Elejalde syndrome--a melanolysosomal neurocutaneous syndrome: clinical and morphological findings in 7 patients.

The number of local and systemic side effects reported with the use and abuse of topically applied corticosteroids in children increases every year. 1-3 Among the main factors responsible are the availability of higher-potency corticosteroids in deeply penetrating vehicles, inadequate knowledge of their side effects, over-the-counter availability, and increased susceptibility of infants and small children to topically applied corticosteroids. 4,5 The following case report is a dramatic example of local and systemic side effects due to misprescription of a topically applied corticosteroid. Report of a Case .—The patient, aged 2 years and 4 months, was the normal product of an uncomplicated pregnancy and normal delivery. He had weighed 3,600 g at birth. At age 11 months, he had suffered an accidental second-degree burn, caused by boiling water, on the neck, pectoral area, and right upper arm. The burned areas had been treated with topical application of a cream containing a

Lourdes Tamayo

Papers

Giant pigmented nevi: clinical, histopathologic, and therapeutic considerations.

Hypomelanosis of Ito: Diagnostic Criteria and Report of 41 Cases

Therapeutic efficacy of interferon alfa-2b in infants with life-threatening giant hemangiomas.

Elejalde syndrome--a melanolysosomal neurocutaneous syndrome: clinical and morphological findings in 7 patients.

Cushing's syndrome after topical application of corticosteroids.