Improved effectiveness of an increased dose of griseofulvin for treating Tinea capitis among refugee children in Israel: A retrospective cohort study.

BACKGROUND: Tinea capitis (TC), a fungal infection that occurs in children, is primarily caused by dermatophytes such as Trichophyton and Microsporum species. For Trichophyton species, treatment with terbinafine is considered more effective than griseofulvin treatment. Specific populations, such as refugee children, are more susceptible to TC. OBJECTIVE: This study aimed to describe and compare the response to treatment among Israeli and refugee children with TC. PATIENTS/METHODS: We retrospectively reviewed data collected on refugee and Israeli children with TC between January 2004 and January 2020. RESULTS: Overall, 3358 children with TC (refugees: 1497; Israelis: 1861) were identified. Among these, 86% of the refugee children had TC caused by Trichophyton violaceum, 65% of the Israeli children had TC caused by Microsporum canis and 83% of all children were treated with griseofulvin. Overall, 14% of the refugees showed a partial response to a griseofulvin dose of ≤25 mg/kg/day; however, they showed a complete response upon increasing the dose to ≥30 mg/kg/day. No significant adverse effects were observed. CONCLUSION: The over-crowded day care centres and dense living make refugee children more susceptible to TC than the general population, and griseofulvin dosage adjustment is necessary. TC, due to Trichophyton species, could benefit from receiving an increased dose of griseofulvin in a suspension form, which is cheaper than terbinafine.

Unusual forms of cutaneous leishmaniasis due to Leishmania major.

BACKGROUND: Cutaneous leishmaniasis (CL) due to Leishmania major (L. major) is common in the Middle East; however, this skin infection may be under-diagnosed when it presents atypically. OBJECTIVE: To highlight the occurrence of uncommon presentations of CL that may elude diagnosis. MATERIALS AND METHODS: A retrospective study was performed among patients who presented at The Sheba Medical Center between 2005 and 2014 with atypical clinical presentations of CL due to L. major. RESULTS: Twelve patients with unusual clinical presentations of L. major CL were identified. All infections were acquired in L. major - endemic areas of Israel. The average age was 37 years. The average number of lesions was 2. Nine patients presented with a form that mimicked other forms of CL, such as lupoid, giant ulcer, sporotrichoid and recidivans, and three had a variant resembling other infectious skin diseases, such as erysipeloid and verruciform. All patients required systemic therapy. CONCLUSION: Cutaneous leishmaniasis due to L. major can masquerade as many other infectious and inflammatory diseases. In addition, it can mimic clinical forms of New World CL. We suggest that in endemic countries or in travellers returning from countries where L. major is endemic, polymerase chain reaction (PCR) for Leishmania-specific DNA should be performed routinely in cases of unusual presentations of dermatitis with a single or a few lesions, even if a diagnosis of CL was not considered by the referring clinician.

Late-onset onchocercal skin disease among Ethiopian immigrants.

BACKGROUND: Onchocerciasis is an infectious disease caused by the filaria Onchocerca volvulus. Very little is known regarding onchocerciasis imported from endemic to nonendemic areas. OBJECTIVES: To evaluate pruritic dermatitis simulating atopic dermatitis in Ethiopian immigrants in Israel. PATIENTS AND METHODS: A retrospective study of 27 Ethiopian immigrants to Israel was conducted. Demographics and clinical and laboratory data were collected. RESULTS: Of the group of 27 patients, 10 (37%) were men and 17 (63%) were women. The average age at referral was 29 years. All of the patients emigrated from Kuwara, Ethiopia. Diagnosis was done by either positive skin snip test or immunoglobulin (Ig) G4 serology of onchocerciasis in 14 patients. The most common presentation was a combination of lichenified onchodermatitis with atrophy and depigmentation (36%). Eosinophilia and elevated IgE levels were common. Seventeen patients were treated with a single administration of oral ivermectin 200 µg mg(-1). Thirteen patients responded to the treatment. CONCLUSIONS: Immigrants from endemic regions to developed countries presenting with pruritic diseases, especially those with a clinical picture suggestive of atopic dermatitis, should be evaluated for possible onchocerciasis infection. Ivermectin, a relatively safe and low-cost treatment, should be considered even in the absence of a proven disease. Physicians should have a high index of suspicion in patients with the corresponding residential history.

Treatment of plaque-type psoriasis with oral CF101: data from an exploratory randomized phase 2 clinical trial.

AIMS: CF101 demonstrated a marked anti-inflammatory effect in Phase 2 studies conducted in patients with rheumatoid arthritis and dry eye syndrome. The aim of this study was to evaluate the safety and efficacy of CF101 for the treatment of patients with moderate to severe plaque-type psoriasis. MATERIALS AND METHODS: This was a phase 2, multicentre, randomized, double-blind, dose-ranging, placebo-controlled study. Seventy five patients with moderate to severe plaque-type psoriasis were enrolled, randomized and treated with CF101 (1, 2, or 4 mg) or placebo administered orally twice daily for 12 weeks. Safety and change from base line of Psoriasis Area and Severity Index (PASI) score and physician's global assessment (PGA) score over 12 weeks. RESULTS: In the 2 mg CF101-treated group, a progressive improvement in the mean change from baseline in the PASI score vs. placebo throughout the study period was observed, with a statistically significant difference on weeks 8 and 12 (P = 0.047; P = 0.031, respectively). In this group, 35.3% of the patients achieved PASI ≥ 50 response, and 23.5% of the patients achieved a PGA score of 0 or 1. CF101 was safe and well tolerated. CONCLUSIONS: CF101 was well tolerated and demonstrated clear evidence of efficacy in patients with moderate to severe plaque psoriasis.

Narrow band UVB: is it effective and safe for paediatric psoriasis and atopic dermatitis?

BACKGROUND: Phototherapy has a time-honoured place in the treatment of variety of skin diseases in adults. The use of this modality in children is limited mainly due to concerns about long-term carcinogenic potential. Only a few clinical trials have been performed on the efficacy and safety of phototherapy in children. OBJECTIVES: To determine the efficacy and safety of NB-UVB phototherapy in children with atopic dermatitis (AD) and psoriasis. METHODS: This is a retrospective review of the treatment outcomes of 129 children with psoriasis and AD, who were treated with NB-UVB between 1998 and 2006 at our institute. RESULTS: Fifty per cent of the psoriatic patients and 25% of patients with AD achieved clearance by the end of the treatment. NB-UVB phototherapy was well-tolerated, with no serious adverse effects except one doubtful case of melanoma in situ. CONCLUSIONS: NB-UVB may be considered as a viable therapeutic option in children with psoriasis and AD. Children who are treated by phototherapy should remain under annual dermatologic observation. To determine true carcinogenic risk of UV therapy, longer follow-up is essential.

Liposomal amphotericin B treatment of cutaneous leishmaniasis due to Leishmania tropica.

BACKGROUND: Cutaneous leishmaniasis (CL) is endemic in Israel, and in the past, has been attributed almost exclusively to Leishmania major. Over the last decade or so, an increase in Leishmania tropica (L. tropica) infections has occurred in several regions of Israel. Topical treatment of Old World CL is usually the rule, however, in some cases systemic treatment is indicated. Liposomal amphotericin B (L-AmB) is efficacious and safe for treating visceral leishmaniasis but its role in treating various forms of CL is yet to be defined. In this study, we summarize the efficacy and safety of L-AmB treatment in a series of Israeli patients with L. tropica infection. METHODS: Cases of PCR-proven CL caused by L. tropica were treated in an outpatient setting. Treatment schedule consisted of five consecutive days of 3 mg/kg L-AmB, followed by a sixth dose on day 10. RESULTS: Thirteen consecutive patients (11 men, two women), received L-AmB. Mean age was 15.3 years; of the 13 patients, 85% had facial lesions. Six had previously failed intralesional sodium stibogluconate treatment and four had failed topical paromomycin treatment. Eleven of 13 patients (84%) achieved complete clinical cure within 2 months. Mean follow-up of 11 months revealed no relapses. Side effects were mild and none terminated treatment prematurely. LIMITATIONS: A non-randomized study, with a small number of patients. CONCLUSION: Liposomal amphotericin B treatment for L. tropica is effective, well tolerated and cost beneficial in countries where cost of hospital-care is significant.

Treatment of cutaneous leishmaniasis with intralesional sodium stibogluconate.

BACKGROUND: Cutaneous leishmaniasis is endemic in Israel. Leishmania major is the most prevalent species that cause cutaneous leishmaniasis. Current treatment options are limited and there are few investigations in search of alternative ones. OBJECTIVE: This study aims to assess our experience with intralesional sodium stibogluconate (SSG) in the treatment of cutaneous leishmaniasis. METHODS: A retrospective evaluation for all adult cases of cutaneous leishmaniasis treated by intralesional and intravenous SSG (Pentostam, GlaxoSmithKline) between 2004 and 2006 was performed, for cases referred to a tertiary care university-affiliated medical centre in Israel. Intralesional SSG was injected at 0.5 mL per lesion (50 mg). Treatment was repeated every 2-3 weeks for a total of 12 weeks. Intravenous SSG was administered at a dose of 20 mg/kg for 10-20 days. RESULTS: Thirty-three cases of cutaneous leishmaniasis were treated with intralesional SSG during the study period. The patients consist of 26 males and 7 females, mostly Israeli military personnel, and there were a total of 93 lesions. Within 3 months from treatment onset, 91% (30/33) had completed healing of the cutaneous lesions after an average of 3 treatments (range 1-6). Side-effects were mild and were mostly pain during injection, with two patients developing mild local site reaction after the injection. CONCLUSIONS: Intralesional SSG treatment is safe, effective and well tolerated with minimal side-effects.

UVB therapy of pityriasis lichenoides--our experience with 29 patients.

BACKGROUND: Pityriasis lichenoides comprises a clinical and pathological spectrum of disorders. So far no highly effective treatment has been reported. Previous small studies have suggested that ultraviolet B (UVB) is a good alternative. METHODS: This is a retrospective analysis of 29 pityriasis lichenoides patients treated in our institution with broad- or narrow-band UVB during the period 1996-2002. Twenty-one of these patients had one or more previous unsuccessful treatments. RESULTS: Complete response was achieved in 93.1% in both treatment groups, with 73% of them still relapse free after a mean follow-up of 58 and 38 months in broad- and narrow-band UVB treatment groups, respectively. Mild side-effects were observed in about one-third of the patients. CONCLUSION: We believe both forms of UVB are a good option for pityriasis lichenoides and should be considered as the first line in generalized cases interested in treatment.

UVB in the management of early stage mycosis fungoides.

BACKGROUND: Several options for treatment of early mycosis fungoides (MF) offer similar success rates. Previous small studies have shown UVB to be at least as effective as PUVA. OBJECTIVE: To summarize our experience with UVB treatment of early MF. METHODS: A retrospective analysis of early-stage MF patients treated by narrow band (NB) or broad band (BB) UVB in our institution between 1996 and 2002. Most patients achieving complete response (CR) were put on maintenance until natural sun exposure was possible and followed up every 3-6 months. The results were compared to those previously reported regarding PUVA. RESULTS: Sixty-eight and 43 patients were treated by NB and BB UVB, respectively. Eighty-six per cent (84 and 89% in NB and BB UVB groups, respectively) of IA and 71% (78 and 44% in NB and BB UVB groups, respectively) of IB patients achieved CR within a mean of 12.8 and 10.6 weeks, respectively. When maintenance was stopped, 65 and 30% had not relapsed after an average follow up of 27 and 222 weeks, respectively. Non-relapse rate was 33 and 48% for those having had vs. those not having had maintenance, respectively. CONCLUSIONS: Our results are comparable to all previously reported for skin-targeted treatments, including PUVA and, to our belief, reflect the nature of early MF, in which CR can probably be achieved in most of the patients. Among the responding patients there is no relapse during prolonged follow-up in about one third of the cases. Thus, we believe treatment should be stopped completely following first CR induction and maintenance treatment should be considered for relapsing patients only. Both broad and narrow UVB options are good and future choices should be made on the basis of short- and long-term side-effects.

Search for germline alterations in CDKN2A/ARF and CDK4 of 42 Jewish melanoma families with or without neural system tumours.

To gain insight into the molecular mechanisms involved in the inherited predisposition to melanoma and associated neural system tumours, 42 Jewish, mainly Ashkenazi, melanoma families with or without neural system tumours were genotyped for germline point mutations and genomic deletions at the CDKN2A/ARF and CDK4 loci. CDKN2A/ARF deletion detection was performed using D9S1748, an intragenic microsatellite marker. Allele dosage at the p14ARF locus was analysed by quantitative real-time PCR employing a TaqMan probe that anneals specifically to exon 1beta of the p14ARF gene. For detecting point mutations, dHPLC and direct sequencing of the coding sequences of CDKN2A/ARF and CDK4 was used. No germline alterations in any of the tested genes were detected among the families under study. We conclude that in the majority of Ashkenazi Jewish families, the genes tested are unlikely to be implicated in the predisposition to melanoma and associated neural system tumours.

Pulsed versus continuous terbinafine dosing in the treatment of dermatophyte onychomycosis.

BACKGROUND: The accepted regimen for terbinafine, one of the most effective treatments for dermatophyte onychomycosis, is continuous administration of 250 mg/day over 16 weeks. A few small studies, however, have raised the possibility of an alternative regimen: pulsed administration of 500 mg/day for 1 week, every 4 weeks (over 16 weeks), without decreasing treatment efficacy. OBJECTIVE: Our aim was to compare the efficacy and safety of both regimens in a large group of patients. METHODS: Retrospective analysis of 260 patients with culture proven dermatophyte onychomycosis treated in seven outpatient clinics run by two dermatologists using one of the terbinafine protocols on a chronological basis: 105 patients were treated using the continuous regimen during 1998/1999 and 155 patients were treated using the pulsed regimen during 1999/2002. Mycological and clinical cure were assessed 2 and 3 months, respectively, after completion of the last therapeutic course. Side effects were documented for the pulse regimen group only and compared with historical data previously published for the continuous protocol. RESULTS: The mycological, clinical and complete (mycological and clinical) cure rates of the toenails were 72.1%, 53.5% and 47.1% in the pulse regimen versus 82%, 35% and 34% in the continuous regimen, respectively (p=0.091, 0.0002 and 0.047, respectively). The mycological, clinical and complete cure rates of the fingernails were 91.7%, 83.3% and 79.2% respectively in the pulse group versus 100% (all parameters) in the continuous group (no significant difference). In general, both regimens were well tolerated and few side effects were reported. CONCLUSION: The pulsed regimen is at least as effective as continuous dosing and thus, at 50% less cost and more convenience, is preferable to a continuous regimen.

Use of sunscreen is linked with elevated naevi counts in Israeli school children and adolescents.

Epidemiological evidence indicates that a fair complexion and exposure to solar radiation in early years contribute to the proliferation of naevi and subsequent melanoma risk. To determine whether protection from sunlight is associated with lower naevi counts, we examined the prevalence and risk factors of naevi in a sample of Israeli school pupils. Whole body counts of naevi were recorded in 974 out of 1312 (74.2%) recruited pupils (7 and 12 year olds) from Ramat-Gan and Jerusalem. Host characteristics and habits of sun exposure were obtained using questionnaires. In each age group and geographic area, the mean whole body naevi counts, adjusted for confounders, were higher among males, pupils of European-American descent, and those susceptible to sunburn. The contributions to naevi risk of fair skin colour and frequent recreational sun exposure were higher among 7 year olds. Regular sunscreen use contributed to the naevi risk for both age strata in Ramat-Gan (at age 7, rate ratio [RR] = 1.7, 95% confidence interval [CI] = 1.3-2.2; at age 12, RR = 1.5, 95% CI = 1.1-2.1). Among the younger age group in Ramat-Gan, even seldom compared with no use of sunscreen was associated with higher naevi counts (RR= 1.5, 95% CI = 1.2-2.0). Similar patterns were noted with the pupils from Jerusalem. In conclusion, the elevated naevi count with increased sunscreen use indicates that sunscreens apparently do not modify the genetic predisposition to naevi proliferation. For better protection of children and adolescents, including those who use sunscreens, from the naevogenic effect of solar radiation, they should be encouraged to limit their exposure and wear protective clothing when in the sun.

A graded work site intervention program to improve sun protection and skin cancer awareness in outdoor workers in Israel.

OBJECTIVES: A graded worksite intervention program to improve sun protection and skin cancer awareness of outdoor workers was implemented and evaluated longitudinally over a period of 20 months. METHODS: Outdoor male workers (144/213 recruits) from geographically separated units of the Israel National Water Company were allocated to complete (n = 37), partial (n = 72) or minimal (n = 35) intervention groups. Subsequent to the assignment and training of local safety officers, an educational and medical screening package was provided to the corresponding groups either once, or repeatedly a year later. Personal sun protective gear was provided upon repeated intervention. Outcome measures were evaluated through self-response questionnaires administered prior to the first intervention pulse, and 8 months after the first and second interventions. RESULTS: A 15-61% improvement in sun-protection habits was noted in the entire study population 8 months after initialization, compared to no sunscreen use, 20% sun-exposed skin area and highest mean occupational exposure dose of 1.68 MED/day at pre-test. An even greater use of sunscreen was evident 1 year later in the complete and partial intervention groups, + 80% and + 52%, respectively. The baseline rate of self-examination of the skin in the same two groups (49%) increased significantly at post-test (+ 71% and + 53%, respectively). CONCLUSIONS: This integrated intervention program led to significantly improved sun protection and skin cancer awareness. Repeated intervention combined with the supply of sun-protective gear contributed to an even greater impact.

Decreased density of epidermal dendritic cells in melanocytic naevi: the possible role of in vivo sun exposure.

Melanocytic naevi are benign skin tumours that originate in the epidermis. The pathogenesis of naevi and cutaneous malignant melanoma has been linked to sun exposure. This study evaluates alterations in the density of immunologically active epidermal dendritic cells (EDCs) in naevi in response to sun exposure. Immunohistologically stained sections of 266 naevi from patients from Israel (n=135) and Germany (n=131) were evaluated. The proportion of naevi with decreased density of HLA-DR+ (dDR+) and CD1a+ (dCD1a+) EDCs was analysed according to country, last exposure to sunlight, anatomical location and histological subtype. The risk of dDR+ was found to be linked to residence in Israel compared with Germany (odds ratio [OR] = 4.2; 95% confidence interval [CI] = 2.0-8.9), suggesting a latitude-dependent effect. Naevi removed in summer had a higher risk of dCD1a+ (OR = 4.7; 95% CI = 2.3-9.8) compared with those removed in winter. The most conspicuous dDR+ among the German cases, and dCD1a+ among the Israelis, occurred in naevi located on commonly exposed skin. The similar densities of EDCs in the lesional and perilesional skin of the majority of the naevi indicates that the underlying naevus cells have no effect on EDC density. It is not unlikely that an altered immune response due to dDR+ and dCD1a+ in sun-exposed skin in the vicinity of naevi contributes to the subsequent melanoma risk in highly susceptible individuals.

Silver-stained nucleolar organizer regions (AgNORs) as a prognostic value in malignant melanoma.

The nucleolar organizer regions (NORs) are chromosomal loops of DNA and proteins involved in ribosomal synthesis. By silver staining, they can be identified as black dots (AgNORs) in the nuclei. Their size and number reflect cell and nuclear activity. Therefore, AgNOR count may correlate with the proliferative activity of tumors. In malignant melanoma, correlation between AgNOR count and the growth phase was found. However, the value of AgNORs in determining prognosis is disputable. Our purpose was to evaluate the role of AgNORs in predicting the biological behavior of melanoma. Paraffin-embedded sections of 30 cases of primary melanoma, 0.4-5 mm thick (mean, 1.6 mm) were stained with silver. Follow-up of all patients was at least 5 years. For each tumor, at least 50 cells were randomly selected for AgNOR count at a final magnification of 500, and the mean of AgNOR content was calculated. Sample parameters corresponded well to the epidemiology and the natural history of melanoma. AgNOR counts (0.78-4.26; mean, 1.42+/-0.72) correlated with tumor thickness (p = 0.01); thus, most superficial tumors had low AgNOR counts, whereas most deep tumors (> or = 1.5 mm) showed high counts. Patients who had tumors with AgNOR counts lower than the median had longer disease-free interval (DFI) than did patients who had tumors with higher counts (p = 0.02). Furthermore, in a multivariate Cox analysis, AgNOR count was independent of tumor thickness in determining DFI (p = 0.05). Therefore, AgNORs may serve as a parameter to predict more accurately the progression of melanomas (mainly thin ones). Larger studies are needed in order to consolidate these preliminary results and to characterize AgNOR value further as a prognostic factor in melanoma.

Prevalence of melanocytic nevi and freckles in young Israeli males. Correlation with melanoma incidence in Jewish migrants: demographic and host factors.

The role of host and environmental factors in the pathogenesis of multiple melanocytic nevi, atypical nevi, and freckles was studied in 1989 in a random sample of 3,040 Israeli males aged 17 years. Multiple melanocytic nevi were significantly associated with family history of melanoma or multiple melanocytic nevi (odds ratio (OR) = 15.0), fair or lightly pigmented skin color (OR = 2.7 and 2.3, respectively), and affiliation to the high or heterogenous melanoma risk group, determined by the incidence rates of melanoma in Jewish migrants from corresponding origin (OR = 3.1 and 2.1, respectively). An environment-related effect may account for the increased multiple melanocytic nevi risk among second- (OR = 8.2) compared with first-generation, native-born recruits (OR = 3.0) from the high melanoma risk group whose families had been living in Israel the longest. Atypical nevi were associated with fair (OR = 6.1) and lightly pigmented (OR = 3.5) skin color, high and moderate sunburn susceptibility (OR = 4.7 and 2.5, respectively), and family history of melanoma or multiple melanocytic nevi (OR = 4.7). Freckles were significantly associated with sun-sensitive phenotype, family history of melanoma or multiple melanocytic nevi (OR = 1.5). Conservative (OR = 1.9) or nonreligious status (OR = 1.9), and high (OR = 2.4) or heterogenous melanoma risk groups (OR = 1.8). These findings indicate that environmental factors may modify the occurrence of multiple melanocytic nevi and freckles in genetically susceptible ethnic groups.

[Acquired torticollis in hospitalized children].

Torticollis results from various pathological mechanisms, and its elucidation depends on identifying diseases of musculoskeletal, neural and ocular tissues. This study characterized the underlying diseases of children hospitalized with torticollis, excluding congenital torticollis. Records of 36 children with torticollis seen during 4 years were reviewed and categorized according to presumed etiology. Most could be classified into 2 categories: in 39% it was due to trauma and in 36% to upper respiratory tract infection. Most girls were in the first group and most boys in the second group. There were 3 cases of ocular torticollis due to superior-oblique muscle palsy, 1 with a post-burn eschar, 2 with neurological disorders (intramedullary cervical astrocytoma and leukodystrophy with macrencephaly), and in 3 no associated cause was found. There was a clear seasonal trend with 58% of cases presenting from November through February, 33% from April through July, and the rest, of neurological or ocular origin, during the rest of the year. In cases of post-traumatic torticollis 21% had neurological symptoms such as weakness of the limbs, headaches or incontinence. Only a few had prior upper respiratory tract infection. All children whose torticollis was assigned to infection had had fever. Only 8% had had neurological complaints or vomiting, half of whom presented with fever exceeding 37.5 degrees C. 46% had restriction of movement and 38% had tenderness. In over 60% of those in this group there were signs of an upper respiratory tract infection, such as lymphadenopathy or a white blood cell count exceeding 15,000/microliter, 3 patients with recurrent torticollis were diagnosed as having severe neurological diseases. Mean hospitalization time was 4 days (range 1-28). Hospitalization periods were similar for all kinds of patients and treatment by traction or fixation did not affect this period.

Familial cutaneous malignant melanoma and tumors of the nervous system. A hereditary cancer syndrome.

BACKGROUND: Excessive risk of cutaneous melanoma as a second cancer has been associated with benign or malignant tumors of the nervous system. Cutaneous melanoma and nervous system tumors may independently aggregate in families. There are, however, no previous reports of increased likelihood of tumors of the nervous system in families of patients with cutaneous melanoma or--of cutaneous melanoma in families with tumors of the nervous system. METHODS: The occurrence of nervous system tumors as second cancers was examined in a series of 904 patients with cutaneous melanoma and/or their family members. RESULTS: Fifteen families with 17 members with cutaneous melanoma from this series had one or more additional relatives with tumors of the nervous system, including astrocytoma, medulloblastoma, glioblastoma multiforme, ependymoma, glioma, meningioma, and acoustic neurilemmoma. Another subgroup of 10 patients with cutaneous melanoma had either a meningioma (n = 9) or acoustic neurilemmoma (n = 1) as a second tumor. The pattern of atypical melanocytic nevi occurring in the majority (20/25) of cutaneous melanoma patients in our series and in additional first degree relatives of 9 of 11 of the affected families, has been previously associated with the Familial Atypical Multiple Mole-Melanoma syndrome. CONCLUSIONS: This unusual familial and personal occurrence of tumors, showing differentiation toward tissues of the neural crest, neuroepithelium, and/or mesenchymal derivation, supports a putative association with a hereditary cancer susceptibility trait.

[Fabry disease: systemic deposition of a glycolipid].

A 20-year-old man was admitted with telangiectatic skin lesions over the lower abdomen, buttocks and genitals and also hypohidrosis and heat intolerance. Fabry disease was diagnosed on the basis of biochemical and histopathological analyses. The concentration of urinary trihexosyl-ceramide was increased but the activity of galactosidase in serum, urine and lymphocytes was marginal. Typical lipid inclusions, showing a concentrically arranged, lamellar osmiophilic structure were identified by electron microscopy in the cytoplasm of endothelial cells from affected skin.