Israel Medical Association Journal

For centuries skin pigmentation has played a major societal role. Genetic disorders of skin pigmentation have therefore always evoked the curiosity of both laypersons and physicians. Normal skin pigmentation is a complex process that begins with the synthesis of melanin within the melanocytes, followed by its transfer to neighboring keratinocytes where it is translocated to the upper pole of the nucleus and degraded as the keratinocyte undergoes terminal differentiation. Mutations in various genes involved in melanocyte migration during embryogenesis, melanin synthesis and melanosomal function and transfer have been shown to cause pigmentation disorders. In the present review, we discuss normal skin pigmentation and the genetic underpinning of selected disorders of hypo- and hyperpigmentation.

Background: With regard to ethnic predilections for Gaucher disease, the most common storage disorder, Ashkenazi Jews are at risk for the non-neuronopathic form (type I), Norbottnian Swedes are at risk for the sub-acute neuronopathic form (type III), and perhaps Arabs are at risk for the very rare cardiac variant of the sub-acute neuronopathic form (type IIIc) for which there is a relatively tight genotype-phenotype correlation. Type II, the acute infantile form, being the rarest form, has not been associated with any ethnic predilection.

Objectives: To examine whether Arab ethnicity influences the Gaucher phenotype.

Methods: We reviewed the records of all Arab patients in a referral clinic of 586 patients in Israel.

Results: There were 46 patients (7.8%) of Arab ethnicity: 23 (50%) had type I disease, 16 (34.8%) had type IIIc disease, 4 (8.7%) had type IIIb disease, and 3 (6.5%) had type II disease. Type IIIc disease was characterized by genotype-phenotype correlation with homozygosity for the D409H (1342C) mutation. All five Bedouin patients (10.9%) had the R48W (C259T) mutation on at least one allele.

Conclusions: For all genotypes, disease severity among Arab patients was relatively similar to that reported among other Caucasian patients. Apparently Arab ethnicity does not impact phenotypic expression in Gaucher disease in a unique manner. The predilection for type IIIc may be a result of consanguinity.
 

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD[1] development in women are limited and conflicting.

Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel.

Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age ≤ 65 years. DNA samples from 235 women served as the control.

Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 ± 7.0 years vs. 48.3 ± 7.5 and 46.3 ± 7.7 years, respectively, P = 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P = 0.037) and Ashkenazi control subjects (23.3%, P = 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 50 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12–13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P = 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI[2] 0.189–1.114) and in women of other origins, 5.84 (95%CI 1.76–19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR[3] 1.42, 95%CI 1.06–1.89).

Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.

Background: Atopic dermatitis or atopic eczema is an itchy inflammatory skin condition with a predilection of the skin flexures. Most cases start in children although some have been reported in adults. Patients with moderate to severe disease refractory to topical corticosteroid or calcineurin inhibitors may require second-line treatment such as phototherapy or systemic immunosuppressants. Methotrexate therapy has been suggested to be a useful immunosuppressant in adult atopic dermatitis.

Objectives: To further determine the efficacy of low dose methotrexate therapy in adults with new-onset atopic dermatitis or with idiopathic eczema.

Methods: All adult patients with new-onset atopic dermatitis or idiopathic eczema treated by methotrexate in our clinics from 2004 to 2006 were included in the study. All had failed prolonged therapy with oral antihistamines and local corticosteroid creams. Methotrexate, 10–20 mg, was given orally once a week along with folic acid supplements 5 days a week. Additional therapies included predominantly emollients. During the entire treatment period the investigators made global assessments of the clinical response.

Results: Nine patients diagnosed with late-onset atopic dermatitis (n=6) or idiopathic eczema (n=3) were treated with methotrexate. All patients responded to the drug. The initial response was noted after 3–7 weeks. Six patients achieved complete remission after 3 months of methotrexate therapy and three patients had significant improvement. One patient's the condition worsened after achieving a complete response while on methotrexate and it was withdrawn completely. No serious adverse events were noted during treatment.

Conclusions: Low dose methotrexate is an effective therapeutic alternative for late-onset atopic dermatitis or idiopathic eczema in patients unresponsive to local and other systemic therapies.
 

Background: Seborrheic dermatitis is a common chronic disease. Malassezia yeasts have been implicated in the pathogenesis of this disease. Antifungal agents are known to be effective in the treatment of Malassezia yeast infections.

Objectives To evaluate the efficacy of itraconazole in the treatment of mild to severe facial seborrheic dermatitis.

Methods: Sixty patients with moderate to severe seborrheic dermatitis were evaluated in an open non-comparative study. Patients were treated with oral itraconazole, initially 200 mg/day for a week, followed by a maintenance therapy of a single dose of 200 mg every 2 weeks. Four clinical parameters (erythema, scaling, burning, itching) were assessed using a 0–3 score. Mycological evaluation determined the presence of Malassezia spores in the scales using a direct smear.

Results: At the end of the initial treatment significant improvement was reported in three clinical parameters: erythema, scaling, itching. Maintenance therapy led to only slight further improvement. Burning sensation was only mildly improved during the treatment. The quantity of Malassezia spores present in the direct smear decreased throughout the treatment period. No blood test abnormalities were found during the treatment.

Conclusions: In this study initial treatment with itraconazole was beneficial in patients with moderate to severe seborrheic dermatitis.

Neonatal lupus erythematosus is an uncommon transplacentally Acquired Autoimmune Disorder. The most common clinical manifestations are skin rash, congenital atrioventricular block, thrombocytopenia, leucopenia, anemia, and hepatosplenomegaly. Usually, the skin rash resembles subacute cutaneous lupus, but different forms of rash have been reported in Neonatal lupus erythematosus and some are rare forms. NLE should be suspected in babies with atypical skin lesions, even if present at birth.