Biomedical subjects
Publications and source records attributed to D Mimouni.
Sarcoidosis is an inflammatory disease with potentially severe mucocutaneous manifestations. Mycophenolate mofetil (MMF) is an immunosuppressive drug extensively used in organ transplantation. Its use has been rapidly expanded into autoimmune and inflammatory diseases. We report the first successful and safe use of MMF in five patients with sarcoidosis.
BACKGROUND: The term 'atrophie blanche' is used both as a descriptive term denoting ivory-white stellate scars on the lower limbs as well as a diagnostic label synonymous with livedoid vasculitis, an ill-defined entity. Medium-sized vasculitides, such as polyarteritis nodosa (PAN), occasionally present with ulceration resulting in ivory-white stellate scarring on the lower limbs and may potentially be misdiagnosed as livedoid vasculitis. OBJECTIVES: To assess the occurrence, clinical and immunopathological features of medium-sized vasculitis in patients presenting with atrophie blanche without clinical and/or compression duplex ultrasonographic evidence of venous insufficiency. METHODS: We retrospectively evaluated patients presenting with atrophie blanche at the Department of Dermatology of Johns Hopkins Medical Institutions, from April 1996 until April 2002, following the diagnostic guidelines for leg ulcers of the Division of Immunodermatology. Deep and multiple skin biopsies were performed for histology. Investigations for underlying vasculitis, thrombophilia, nerve conduction studies and compression duplex ultrasonography of the lower extremities were performed in all patients. RESULTS: Of 29 consecutive patients presenting with atrophie blanche, six had underlying medium-sized vasculitis consistent with PAN, three of whom had previously been diagnosed to have segmental hyalinizing vasculitis/vasculopathy (livedoid vasculitis/vasculopathy) on superficial biopsies. All six patients with cutaneous PAN were women with a median age of 36.5 years (range 34-46) and with a median duration of the disease prior to diagnosis of 18 years (range 3-30). Of the six cutaneous PAN patients, four had neurological involvement evidenced by clinical symptoms and nerve conduction studies. No evidence of any other extracutaneous involvement was found. Erythrocyte sedimentation rate and tests for vasculitis and thrombophilic were normal in all six patients. None had evidence of venous insufficiency. Immunosuppressive therapy was effective in controlling PAN-associated cutaneous and neurological disease. Of the remaining 23 patients, two had antiphospholipid syndrome and one had homocystineaemia; all three also had evidence of venous insufficiency. One patient had multiple myeloma-associated type I cryoglobulinaemia and 19 patients had venous insufficiency alone. None of the non-PAN patients had abnormalities in the nerve conduction studies. CONCLUSIONS: In patients presenting with atrophie blanche without evidence of venous insufficiency and thrombophilia, PAN should be excluded, particularly in the presence of mononeuritis multiplex. Repeated and deep biopsies are often necessary to reveal the accurate underlying pathology of necrotizing medium-sized vasculitis in the reticular dermis and the subcutis, especially in the setting of atrophie blanche lesions. Immunosuppressive therapy was effective in controlling the PAN-associated clinical manifestations.
Peristomal pyoderma gangrenosum (PPG) is a variant of pyoderma gangrenosum (PG) that is more refractory to treatment. It is a cause of severe morbidity and poses a therapeutic challenge for the clinician. Infliximab (Remicade(R); Centocor, Malvern, PA, USA) is a chimeric monoclonal antibody directed against tumour necrosis factor-alpha that has been proven to be effective in the treatment of inflammatory bowel disease (IBD) and rheumatoid arthritis. Currently, very few reports exist documenting its use in the treatment of PG and none in the treatment of PPG. We describe our experience of treating three patients with IBD-associated PPG with infliximab. All patients tolerated the drug without significant side-effects. Two patients with PPG recovered completely following the administration of infliximab, and one patient had a partial response to the drug. We conclude that infliximab appears to be a safe and effective therapeutic alternative in patients with PPG.
BACKGROUND: Scabies is not a notifiable disease in most countries. Therefore, its seasonality trends are usually estimated and may be inaccurate. OBJECTIVES: To determine the seasonality of scabies over the long term in a large military population, including all of the Israel Defence Forces personnel. METHODS: For the last two decades, the Israel Defence Forces have mandated the routine reportage of every case of scabies infestation in soldiers to the Epidemiology Department of the Army Health Branch. This database was used in the present study to analyse the incidence of scabies by season. Scabies was defined according to the report by a military physician based on the typical clinical presentation, relevant epidemiological data and, in most cases, microscopic visualization of the mite. RESULTS: The person-time incidence of scabies was higher in winter than summer (P < 0.001). The overall risk ratio was 1.31 (95% confidence interval 1.28-1.33). Sensitivity analysis indicated that no single year was an important source of disease heterogeneity. CONCLUSIONS: Scabies in a young adult population is more frequent in the cooler months of the year.
BACKGROUND: Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease associated with specific B-cell lymphoproliferative neoplasms. There has been an increasing number of individual reports in the childhood and adolescent population. OBJECTIVES: To examine the clinical and immunopathological features of PNP occurring in children and adolescents. PATIENTS AND METHODS: We analysed the clinical and immunopathological findings of 14 patients under the age of 18 years with a confirmed diagnosis of PNP. Sera from all patients were analysed by indirect immunofluorescence (IF) and immunoprecipitation for plakin autoantibodies, immunoblotting for detection of plectin autoantibodies, and enzyme-linked immunosorbent assay (ELISA) for the detection of desmoglein (Dsg) 1 and Dsg3 autoantibodies. RESULTS: Severe oral mucositis was observed in all patients, and lichenoid cutaneous lesions in eight of 14 patients. The average age at presentation was 13 years. Striking findings included: pulmonary destruction leading to bronchiolitis obliterans in 10 patients, association with Castleman's disease in 12 patients, and a fatal outcome in 10 patients. The underlying neoplasm was occult in 10 patients. Histological findings include lichenoid and interface dermatitis with variable intraepithelial acantholysis. Deposition of IgG and C3 in the mouth and skin by direct IF was not found in some cases, but indirect IF detected IgG autoantibodies in all cases. Immunoprecipitation revealed IgG autoantibodies against desmoplakin I, envoplakin and periplakin in all cases, and against desmoplakin II and the 170-kDa antigen in 13 and 10 patients, respectively. Dsg3 and Dsg1 autoantibodies were present in 10 and three patients, respectively, and plectin autoantibodies in 13 patients. CONCLUSIONS: PNP in children and adolescents is most often a presenting sign of occult Castleman's disease. It presents with severe oral mucositis and cutaneous lichenoid lesions. Serum autoantibodies against plakin proteins were the most constant diagnostic markers. Pulmonary injury appears to account for the very high mortality rates observed.
BACKGROUND: It is not mandatory to report Pediculosis capitis and Phthirus pubis in most countries; therefore, little is known about the seasonality of these infestations. METHODS: We analysed the data based on routine and mandatory reporting of every case of Pediculosis capitis and Phthirus pubis to the Army Health Branch Epidemiology Department, Israel, over the last two decades. RESULTS: The average 20-year incidence of Pediculosis capitis shows a significant rise during the warmer months (R2 = 0.692, P < 0.05) with a parallel significant decrease in the cooler months (R2 = 0.893, P < 0.05). The results for Phthirus pubis show a significantly higher person-time incidence in the winter (P < 0.001). Sensitivity analysis to investigate possible sources of heterogeneity during this time indicated that no single year was an important source of heterogeneity. CONCLUSIONS: Pediculosis capitis is more frequent in the warmer months, whereas Phthirus pubis is more dominant in the cooler months.
UNLABELLED: The effect of breastfeeding on the development of allergic rhinitis and other atopic conditions has been assessed in many studies but remains controversial. To elucidate this issue, a systematic review was conducted of prospective studies that evaluated the association between exclusive breastfeeding during the first 3 mo after birth and allergic rhinitis. The 1966-2000 MEDLINE databases were searched and the reference lists of relevant articles were reviewed according to predetermined inclusion criteria. The methodological aspects of each study, duration and exclusivity of breastfeeding, outcome measures, control for potential confounding variables and other factors were assessed, and estimates of the association between breastfeeding and allergic rhinitis were abstracted independently by the investigators using a standardized approach. Six prospective studies met the inclusion criteria. The summary odds ratio for the protective effect of breastfeeding was 0.74 (95% confidence interval 0.54-1.01). The effect estimate in studies of children with a family history of atopy was 0.87 (95% confidence interval 0.48-1.58). CONCLUSION: Exclusive breastfeeding during the first 3 mo after birth protects against allergic rhinitis in children, both with and without a family history of atopy. The protective association, although of borderline statistical significance, was substantial. Larger prospective studies with strict methodology and longer periods of follow-up are needed.
A serologic survey was conducted on a population-based representative sample of 521 18-year-old soldiers recruited to the Israel Defence Forces in 1997. The prevalence of neutralizing antibodies and geometric mean titers (GMTs) against the three types of poliovirus (Mahoney, MEF and Saukett strains) were found to be 98.7% (GMT--169.95), 99.6% (GMT--297.14) and 96.4% (GMT - 59.48), respectively. These GMTs are markedly lower than those recorded 4 years after booster vaccination carried out during a 1988 polio outbreak, and suggest a decline in immunity against polio among young adults. These findings support the policy of routine revaccination of children and adolescents in countries at risk of imported polioviruses and of revaccination of adults traveling to areas to which polio is endemic.
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We describe four patients with mycosis fungoides (MF) in whom depigmentation, and also leucotrichia in one, occurred following the resolution of the eruption during phototherapy (psoralen plus ultraviolet A treatment in three patients, climatotherapy in one). In all cases, the depigmentation was localized to the area of the pre-existing MF lesions. There was no clinically obvious phototoxicity. Biopsy study including S100 staining in all cases, and electron microscopy in one case, demonstrated the total absence of melanocytes, with no evidence of MF. It is suggested that the phototherapy may have activated a cell-mediated immunity leading to destruction of the melanocytes. We recommend that vitiligo-like leucoderma be added to the list of untoward effects of phototherapy in MF.
BACKGROUND: Pediculosis capitis and pubis are not mandatorily reported diseases in most countries. Thus, the reported rates of these diseases in large populations are usually inaccurate and based on estimations. OBJECTIVE: To describe the global epidemiology of pediculosis capitis and pubis in the Israeli Defense Force. METHODS: We analyzed the data obtained from the routine and mandatory reporting of every individual case of pediculosis capitis and pubis to the Army Health Branch Epidemiology Department since 1972 and 1973, respectively. RESULTS: During this period, epidemics of pediculosis capitis and pubis were observed between 1973 and 1985 and 1972 and 1987, with 17.7- and 3.9-fold increases in incidence, respectively. These two epidemics were followed by a sharp decline in morbidity (113.6- and 13.6-fold between 1981 and 1999 and 1984 and 1999, respectively) to the present. CONCLUSIONS: A number of factors could be responsible for the observed decline in morbidity, e.g. socioeconomic, pharmacologic, environmental, or prevention policy modifications. The rates of pediculosis capitis and pubis have continuously declined since the last epidemic of 1972-1987, indicating the influence of these and possibly other factors.
BACKGROUND: Despite the numerous studies on the possible protective effect of breast-feeding against the onset of atopic dermatitis during childhood, this issue remains controversial. OBJECTIVE: We conducted a systematic review with meta-analysis of prospective studies that evaluated the association between exclusive breast-feeding during the first 3 months after birth and atopic dermatitis. METHODS: A comprehensive search of the 1966-2000 MEDLINE database and review of the reference lists of relevant articles identified 18 prospective studies that met the predefined inclusion criteria. By means of a standardized approach, 2 of the investigators independently assessed the methodologic quality of the studies, duration and exclusivity of breast-feeding, outcome measures, and control for potential confounding factors. The same approach was applied during data abstraction and evaluation of the estimates of association. Summary measures of association were then calculated. RESULTS: The summary odds ratio (OR) for the protective effect of breast-feeding in the studies analyzed was 0.68 (95% confidence interval [CI], 0.52-0.88). This effect estimate was higher in the group of studies wherein children with a family history of atopy were investigated separately (OR = 0.58; CI, 0.41-0.92) than in those of combined populations (OR = 0.84; CI, 0.59-1.19). A small subset of studies of children without a history of atopy in first-degree relatives showed no association between breast-feeding and the onset of atopic dermatitis (OR = 1.43; CI, 0.72-2.86). CONCLUSION: Exclusive breast-feeding during the first 3 months of life is associated with lower incidence rates of atopic dermatitis during childhood in children with a family history of atopy. This effect is lessened in the general population and negligible in children without first-order atopic relatives. Breast-feeding should be strongly recommended to mothers of infants with a family history of atopy, as a possible means of preventing atopic eczema.
BACKGROUND: The protective effect of breast-feeding on the development of childhood asthma remains a matter of controversy. We conducted a systematic review of prospective studies that evaluated the association between exclusive breast-feeding during the first 3 months after birth and asthma. STUDY DESIGN: We searched the 1966-1999 MEDLINE database and reviewed reference lists of relevant articles to identify 12 prospective studies that met pre-stated inclusion criteria. Methodological aspects of the studies, duration and exclusivity of breast-feeding, and outcomes were assessed. Effect estimates were abstracted by the investigators, using a standardized approach. RESULTS: The summary odds ratio (OR) for the protective effect of breast-feeding was 0.70 (95% CI 0.60 to 0.81). The effect estimate was greater in studies of children with a family history of atopy (OR = 0.52) than in studies of a combined population (OR = 0.73). CONCLUSIONS: Exclusive breast-feeding during the first months after birth is associated with lower asthma rates during childhood. The effect, caused by immunomodulatory qualities of breast milk, avoidance of allergens, or a combination of these and other factors, strengthens the advantage of breast-feeding, especially if a family history of atopy is present.
We compared cost-benefit and cost-effectiveness analyses of hepatitis A prevention with immune serum globulin (ISG) vs inactivated hepatitis A vaccine (iHAV) in the Israel Defence Forces. Personnel were grouped according to conditions and duration of service and analyses were performed based on maximum and minimum hepatitis A projected incidences for each group. For standing army soldiers in field units, iHAV is economically superior compared with ISG. For the five other groups studied, the reverse is true. Expected increases in production costs of ISG and expected decreases in costs of iHAV are likely to make iHAV more economical in the future.
During the 50's and 60's there were large scale epidemics of hepatitis A every 3-4 years in the Israel Defense Forces. During these epidemics the annual incidence exceeded 10/1000 soldiers at risk. There has been a highly significant decrease in rates during the past 30 years. The average annual incidence of clinically identified viral hepatitis A decreased from an average of 6/1000 during the 60's to 2.5/1000 during the 70's. The decrease coincided with the introduction in the 1970's of wide-scale post-exposure prophylaxis with immune serum globulin (ISG). The incidence was further significantly reduced to 0.5-1.0/1000 with the introduction of pre-exposure prophylaxis with ISG, starting in 1978 (p < 0.001). Other factors probably played a role in accelerating the decline in morbidity, such as improvement in personal hygiene and sanitation facilities, and in waste disposal and other aspects of military environmental health. These improvements were probably more pronounced in the civilian sector, leading to decreased exposure of children to the virus and consequently a higher proportion of seronegatives at induction. Increase in the proportion of recruits without natural immunity to the virus poses greater risk, both in terms of personal morbidity as well as military operational ability. This risk, combined with problems of ISG use and availability, has propelled hepatitis A prevention policy towards the use of the new inactivated vaccines.
BACKGROUND: Measles vaccination at ages 12-15 months is a routine part of standard health care in developed countries. Nonetheless, the prevention and control of measles outbreaks remain a challenge, owing to incomplete or variable compliance with immunization programs and primary vaccine failure (approximately 5%). In Israel, vaccination coverage against measles is high, yet sero-epidemiological studies conducted in the early 1990s showed that 15% of 18-year-olds were unprotected. METHODS: 1994 there was a countrywide epidemic of measles, which spread to the military. The Israel Defense Forces Medical Corps immediately launched a wide-scale vaccination campaign, targeting primarily field units and training bases, where crowded living conditions are the rule. RESULTS: The immunization campaign led to an abrupt cessation of morbidity in the military. In the civilian sector, where no intervention was undertaken, the epidemic continued for another 4 months. CONCLUSIONS: Institutional measles outbreaks, especially in the presence of crowded conditions or high contact rates, may be effectively controlled by mass vaccination.
BACKGROUND: Over a period of 4 days between May 18-21, 1998, a multifocal outbreak of diarrhea, involving 175 Israel Defence Force soldiers and at least 54 civilians, occurred in the Golan Heights. PATIENTS AND METHODS: Stool samples from 40 affected soldiers were collected for microbiological testing. In addition, a rapid PCR technique was employed for the direct detection of the heat-labile (LT) and heat-stable toxin (ST) genes of enterotoxigenic Escherichia coli (ETEC) in stool samples. RESULTS: All 40 stool specimens taken from patients with diarrhea was negative by culture. However, ETEC was detected in 16 stool specimens using the rapid PCR method. The epidemiological investigation found no association between the food items consumed prior to the onset of the outbreak and the attack rate of diarrhea. A review of the water distribution system revealed that all affected military posts and civilian communities were supplied by a common water pipeline. Water sampled from various points along the distribution system showed inadequate chlorination and high concentrations of E. coli. CONCLUSION: This report suggests that the involvement of ETEC in the etiology of waterborne diarrheal outbreaks may be underestimated, probably due to the difficulties involved in the laboratory identification of this enteropathogen. Adoption of our rapid method for the identification of ETEC, which is applicable to routine diagnostic laboratories, facilitates pathogen detection within hours, and allows early intervention in cases of widespread diarrheal epidemics.
Animal rabies is endemic in Israel, with 50-80 laboratory-confirmed cases being diagnosed annually. Despite the high incidence among animals, human rabies has not occurred in Israel for almost four decades. This is likely due to the highly effective prevention policy implemented by the Ministry of Health, based on pre-exposure vaccination of populations at risk, post-exposure treatment, and updated rules. Notwithstanding the previous success, a human case occurred in 1996 when a soldier was bitten, while asleep, by an unidentified small animal, which according to his description was a rat or a mouse. Since injuries by these rodents do not require antirabies treatment, no antirabies post-exposure prophylaxis was administered. Five weeks later the soldier complained of fever and nausea with interchanging periods of rage and calm, confusion, and water aversion. His condition deteriorated gradually, leading to deep coma and death. Immunofluorescence examination of a skin biopsy was positive for rabies, and PCR of saliva revealed Lyssavirus genotype 1. We review the changes in the epizootiology of rabies in Israel, the trends of human exposure to animals, and the pre- and post-exposure prophylaxis guidelines, and discuss possible measures that could have been undertaken to prevent the eventuality of this case. This case of rabies, the first after a long period without human disease, accentuates the importance of strict adherence to prevention guidelines. Considerations of geography, epidemiology, and the circumstances of exposure are crucial in the treatment decision-making process.