[Cutaneous leishmaniasis following military deployment to Iraq]. / Leishmaniose cutanée au cours du déploiement militaire en Irak.

Cutaneous leishmaniasis (CL) is a parasitic disease of the tropics and subtropics, transmitted by bites of infected female phlebotonine sandflies. Although CL lesions are normally self-healing they may be disfiguring or potentially disabling, and in field conditions may become secondarily infected; clinical intervention is appropriate in these circumstances. We describe two soldiers normally stationed in British Forces Germany who following deployment to Iraq presented with Leishmania tropica infection. The primary prevention of CL is discussed, together with the epidemiology of the disease, and its treatment under deployed conditions. Old World CL rarely requires aggressive antimonial terapy. Antiiosis with or without curettage is a simple, safe and effective field treatment.

Defective integrin alpha 6 beta 4 expression in the skin of patients with junctional epidermolysis bullosa and pyloric atresia.

Junctional epidermolysis bullosa (JEB) is a heterogeneous group of rare inherited skin disorders in which defects in cell adhesion components cause incomplete formation of hemidesmosomes. We have immunohistochemically examined the skin from ten JEB patients (JEB gravis, n = 4; JEB mitis, n = 3; JEB plus pyloric atresia [JEB/PA], n = 3) using monoclonal antibodies specific for the integrin adhesion receptors alpha 3 beta 1 and alpha 6 beta 4, and for the alpha 3, beta 3, and gamma 2 subunits of the basement membrane ligand, laminin 5. Consistent with our previous reports, only the JEB gravis patients without associated pyloric atresia expressed reduced or absent epitopes for laminin-5 subunits in their epidermal basement membrane. In contrast, all three JEB/PA cases showed abnormalities in integrin alpha 6 beta 4, but not in laminin 5, expression in their basal epidermal cells. Integrin beta 4 subunit was undetectable in the biopsied epidermis of these JEB/PA individuals using five different monoclonal antibodies that recognize both intra- and extracellular epitopes. The absence of the beta 4 subunit in the epidermis of JEB/PA specimens was confirmed by Western blot analysis of tissue extracts. Epidermal expression of the integrin alpha 6 subunit was variable in the JEB/PA patients. Abnormal integrin alpha 6 beta 4 expression may define the subset of JEB cases with pyloric atresia. These results strongly implicate a functional role for alpha 6 beta 4 in the formation of complete hemidesmosomes and in stable adhesion of basal keratinocytes to the basement membrane in vivo.

Atrichia with papular lesions resulting from a nonsense mutation within the human hairless gene.

Atrichia with papular lesions is a rare autosomal recessive form of alopecia characterized by hair loss soon after birth and the development during childhood of a diffuse papular rash. We have previously shown that this disorder results from a deleterious mutation in the human hairless gene, a gene also involved in the pathogenesis of a related but clinically distinct form of congenital alopecia, termed alopecia universalis congenita. In this report, we describe a novel nonsense mutation in exon 4 of the human hairless gene in a consanguineous kindred affected with atrichia with papular lesions. This report provides additional evidence for phenotypic heterogeneity among inherited atrichias and for an association between the papular rash of atrichia with papular lesions and nonsense mutations in the human hairless gene.

Association of an apolipoprotein B gene marker with essential hypertension.

We designed an association (retrospective, case control) study aimed at evaluating associations between genetic variations of the human apolipoprotein B (apoB) gene and clinical diagnosis of essential hypertension. Our approach was to compare the distribution of the alleles of a highly polymorphic variable number of tandem repeats localized 3' to the human apoB gene, the apoB 3' hypervariable region (HVR), in a group of normotensive and a group of hypertensive individuals. We collected DNA samples from 437 unrelated nationals (215 normotensives and 222 hypertensives) from the United Arab Emirates (UAEs), and we determined their apoB 3' HVR allele and genotype status with a polymerase chain reaction-based assay. In the UAE population, we found 18 alleles underlying a total of 51 genotypes. The distribution of these alleles was significantly different between normotensive and hypertensive UAE nationals. The main peak of the distributions occurred at 35 repeats among hypertensives (with a relative frequency of 25.7% versus 19.6% in normotensives) and at 37 repeats among normotensives (28.8% versus 20.3% in hypertensives). Alleles with 21, 23, 25, 49, and 55 repeats were found in hypertensives only (with a combined relative frequency of 7.6%). We conclude that variations of the apoB gene, or of a nearby gene, that may be in linkage disequilibrium with these alleles play a role in the development of essential hypertension in the UAEs.

Congenital ichthyosis, follicular atrophoderma, hypotrichosis, and hypohidrosis: a new genodermatosis?

Follicular atrophoderma is a rare anomaly observed mainly in the X-dominant form of chondrodysplasia punctata (Conradi-Hünermann-Happle syndrome) and in the X-linked dominant Bazex syndrome. We report on five Emirati sibs (three girls and two boys), 4-18 years old, with normal stature, diffuse congenital ichthyosis, patchy follicular atrophoderma, generalized and diffuse non-scarring hypotrichosis, and marked hypohidrosis. Steroid sulfatase activity, assessed in the two boys, was found to be normal. Electron microscopic studies of ichthyotic skin did not show any specific abnormality. The association of congenital diffuse ichthyosis with follicular atrophoderma and hypotrichosis has not been reported before. The patients were reminiscent of Bazex syndrome; however, ichthyosis is not a component of Bazex syndrome. We conclude that this syndrome of congenital ichthyosis with follicular atrophoderma represents a new autosomal recessive genodermatosis.

Association study between the ANF gene and hypertension in a Gulf Arab population.

We have studied an insertion/deletion (I/D) dimorphism located in the second intron of the human atrial natriuretic factor (ANF) gene among 232 United Arab Emirates (UAE) nationals (112 normotensives and 120 hypertensives) from the Abu Dhabi Emirate, with a view to evaluating the value of this marker in relation to hypertension. Our findings show that genotype frequencies of this I/D marker occur in Hardy-Weinberg proportions (respective genotype frequencies in the overall sample population are: II, 51%; ID, 42%; DD, 7%). No association, however, was evidenced between this dimorphic site and clinical diagnosis of essential hypertension. This suggests that: 1) this I/D dimorphism is not a useful marker to study the relationship between the ANF gene and hypertension in the UAE; and 2) variations of the ANF gene that may be in linkage disequilibrium with this marker do not play a major role in the determination of hypertension in this Arab population.

An MboI two-allele polymorphism may implicate the human renin gene in primary hypertension.

As a key enzyme of the renin-angiotensin-aldosterone system, the renin gene (REN) is a good candidate quantitative trait locus that may be implicated in the molecular etiology of essential hypertension. Among mixed reports on the subject, a REN MboI restriction fragment length polymorphism has been shown to be significantly associated with a family history of hypertension in a Japanese population. We show here that the REN MboI dimorphic site is located in the ninth intron of the gene, and we describe a polymerase chain reaction-based assay for detection of this site. We investigated MboI genotype distributions in 331 hypertensive and 279 normotensive subjects from the United Arab Emirates (UAE), a genetically homogeneous ethnic population with no history of smoking or alcohol consumption. A statistically significant association was found between alleles on which the MboI site is present and clinical diagnosis of essential hypertension, indicating that 1) the presence of the MboI site is a marker for susceptibility to hypertension in the UAE (the associated odds ratio is 3.16); and 2) variations of the REN (or of a nearby) gene that may be in linkage disequilibrium with this marker play a role in the development of essential hypertension in the UAE.

Porokeratosis punctata palmaris et plantaris. A new entity?

Seven members from three generations of a Saudi family presented with porokeratosis punctata palmaris et plantaris (PPPP). In our series of patients, the disorder began in their early 20s, seemed to be transmitted as a dominant trait, and affected males only. The elementary lesion was a tiny keratotic spine, and the involvement was strictly limited to the volar aspects of the hands and to the soles of the feet. Histological studies showed a columnar parakeratosis that resembled the cornoid lamella of porokeratosis, but other clinical and histological traits tended to make PPPP an entity that was distinct from true porokeratosis. There have been only six reports in the literature on genuine PPPP before this series.

The pyloric atresia-junctional epidermolysis bullosa syndrome. Report of a case and review of the literature.

BACKGROUND AND METHODS: The concomitant occurrence of the two rare conditions of pyloric atresia (PA) and inherited epidermolysis bullosa (EB) is not as rare as would be expected. We collected 41 case reports in the world literature and add a personal case in which EB was investigated with modern methods and found to be a GB3-positive/non-Herlitz junctional variant. OBSERVATIONS: Our review of the PA-EB association discloses that it is an autosomal recessive inherited entity in which EB is of the junctional EB (JEB) subtype and PA is a primary manifestation rather than a scarring process secondary to JEB. The disease is thus better called "PA-JEB." Patients with the PA-JEB syndrome present, not uncommonly, with erosions and/or subepithelial cleavage in the respiratory, gastrointestinal, and urinary tracts. In addition, certain facultative features are unique to PA-JEB, ie, obstruction of the ureterovesical junction and high incidence of a peculiar form of aplasia cutis congenita. CONCLUSION: The GB3 monoclonal antibody was found normally expressed in three of three cases, excluding the Gravis-Herlitz variant, in spite of an unmatching EB phenotype in one case. Further studies are needed to assess which of the JEB varieties are present in the PA-JEB syndrome.

Haplotypes of the human renin gene associated with essential hypertension and stroke.

The human renin gene (REN) is a good candidate in studies aimed at unravelling the genetic basis of essential hypertension and stroke. We previously established that both a BglI and an MboI dimorphisms (located respectively in the first and ninth introns of the REN gene) were associated with essential hypertension in a population of hyperlipidaemic US subjects. In this association (retrospective case-control) study, we investigated the haplotype distribution of alleles defined by the combination of REN BglI and MboI dimorphic sites in 329 hyperlipidaemic US Caucasian subjects referred to UCSF Medical Center (140 hypertensives, 141 normotensives, and 48 hypertensive patients who had suffered a stroke). A statistically significant association was found between alleles determined by both (BglI(-)/MboI(+)) and (BglI(+)/MboI(+)) haplotypes and clinical diagnosis of EHT (combined odds ratios, OR = 3.35, corrected P < 10(-7)). Haplotypes (-,+) and (+,+) were also found to be associated with clinical diagnosis of stroke (OR = 4.31, P < 10(-7)). These associations do not occur through the effects of classical risk factors related to lipid, lipoprotein and apolipoprotein levels. We conclude that variations of the REN (or of a nearby) gene that may be in linkage disequilibrium with REN (BglI(-)/MboI(+)) and (BglI(+)/MboI(+)) alleles could play a role in contributing to increased individual's genetic susceptibility to EHT and to stroke. Journal of Human Hypertension(2001) 15, 49-55

Association of acanthosis nigricans with risk of diabetes mellitus, and hormonal disturbances in arabian females: case-control study.

OBJECTIVE: To aim of the present study is to determine the association of acanthosis nigricans(AN) with risk of diabetes mellitus, and hormonal levels in female subjects from the United Arab Emirates (UAE). DESIGN: Matched case-control study. SETTING: Tawam Teaching Hospital of Faculty of Medicine and Health Sciences. SUBJECTS: 184 female subjects (92 females with AN and 92 females without AN); (age range 16-65 years) were recruited. METHODS: Height, weight, and sitting blood pressure were recorded on 184 female subjects with AN and without AN. Fasting blood samples were obtained for measurement of uric acid, glucose, cholesterol, HDL-cholesterol, and triglyceride levels. MAIN OUTCOME MEASURE: Risk factors were investigated. Analysis was based on univariate and multivariate analysis. RESULTS: The present study showed that BMI, family history of DM, fasting glucose, HDL-cholesterol (mmol/l), triglycerides (mmol/l) and uric acid (mmol/l) levels were statistically significantly higher in obese women in acanthosis and non acanthosis groups. The results revealed that BMI, family history of DM, total cholesterol (mmol/l), triglycerides (mmol/l) and uric acid (mmol/l) levels were statistically significant higher in diabetic women in non-acanthosis. Furthermore, systolic blood pressure, total cholesterol (mmol/l), triglycerides (mmol/l) and uric acid (mmol/l) levels were statistically significantly higher in diabetic women in acanthosis groups. Overall, DM subjects had significantly higher values for hormone levels of TSH, FSH, LH, progesterone, testosterone, cortisol, prolactin, GH, and ferritin. CONCLUSION: The conclusion has been stated as follows: patients in the UAE who have AN have a high prevalence of DM and insulin resistance. Since AN is rather prevalent in the UAE, identifying this skin lesion can help detect those subjects with a higher risk of DM and hormonal disturbances.

Congenital insensitivity to pain with anhidrosis.

Congenital insensitivity to pain with anhidrosis is an autosomal-recessive disorder resulting from defective neural crest differentiation with loss of the first-order afferent system, which is responsible for pain and temperature sensation. There is also a neuronal loss in the sympathetic ganglia. Lack of sweating, hyperthermia, and infections of bones are main features of the disorder; however, contradictory results have been published regarding eccrine sweat gland innervation. A 5-year-old male patient with typical clinical manifestations of congenital insensitivity to pain with anhidrosis is presented. Immunohistochemistry with antibodies against S100 protein and neuron-specific enolase failed to reveal nerve fibers in the vicinity of the eccrine sweat glands. The roles of the nerve growth factor and tyrosine kinase receptor gene mutations in the pathogenesis of the disease are also discussed.

Association of Acanthosis nigricans with risk of diabetes mellitus and hormonal disturbances in females.

OBJECTIVE: To determine the association of Acanthosis nigricans, hyperinsulinemia, and hormonal levels in female subjects from the United Arab Emirates (UAE). DESIGN: Prospective study. SETTING: Tawam Teaching Hospital of Faculty of Medicine & Health Sciences. SUBJECTS: Ninety-two females (age range 16-65 years) were recruited. METHODS: Height, weight, and sitting blood pressure were recorded on 92 female subjects with A. nigricans. Fasting blood samples were obtained for measurement of uric acid, glucose, cholesterol, high-density lipoprotein- (HDL) cholesterol, and triglyceride levels. Serum levels of thyroid stimulating hormone (TSH), testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin are obtained by radio-immunoassay. RESULTS: Ninety-two females with A. nigricans were enrolled in the study. Of the 92 females, 36 subjects were considered to have diabetes mellitus (DM) and 56 euglycemic subjects. The analysis showed that in cases of family history of DM, HDL-cholesterol (mmol/l) and uric acid (mmol/l) levels were higher. Overall, DM subjects had significantly higher values for hormone levels of TSH, FSH, LH, progesterone, testosterone, cortisol, prolactin, (growth hormone) GH, and ferritin. CONCLUSION: Patients with A. nigricans have a high prevalence of DM and insulin resistance in UAE. Since A. nigricans is rather prevalent in the UAE, identifying this skin lesion can help detect those subjects with a higher risk of DM and hormonal disturbances.

Larsen syndrome in siblings with consanguineous parents.

Two siblings with Larsen syndrome and consanguineous parents are described, both with multiple joint dislocations and the typical facial appearance. Short stature is marked in both children and one had a diaphragmatic hernia which has not been previously described in this condition.

Acanthosis nigricans, hyperinsulinaemia and risk factors for cardiovascular disease.

We examined the association between acanthosis nigricans, hyperinsulinaemia and other risk factors for cardiovascular disease in patients from the United Arab Emirates. Height, weight and sitting blood pressure were recorded in 122 patients with acanthosis nigricans, and blood samples were obtained for measuring fasting cholesterol, high-density lipoprotein cholesterol, triglyceride and uric acid levels. In addition, a glucose tolerance test was performed and blood was sampled for insulin and glucose. Our results indicate that the patients with acanthosis nigricans had a high prevalence of abnormal glucose tolerance and hyperinsulinaemia. In addition, euglycaemic patients with hyperinsulinaemia had a cluster of risk factors for cardiovascular disease.

Etiology of toe-web disease in Al-Ain, United Arab Emirates: bacteriological and mycological studies.

We examined and sampled 45 patients with toe-web intertrigo for bacteriological and mycological studies. Prominent isolated pathogens were the genus Candida (57.7%), genus Aspergillus (28.8%), Pseudomonas aeruginosa (26.7%) and coliforms (24.4%). Dermatophytes scored 4.4% (Trichophyton rubrum). There were 43 patents (95.5%) who presented with marked hyperkeratosis and maceration of the toe-webs involved. The tradition of the Emirati population of sitting cross-legged may, over time, induce in the toe-webs of overweight individuals a macerated pressure-reaction hyperkeratosis that is colonized by environmental germs. T. rubrum and T. mentagrophytes are uncommon in the Al-Ain environment and this may explain the rarity of dermatophytes in toe-web intertrigo in our study.

Analysis of the apolipoprotein B gene 3' hypervariable region among nationals of the Abu Dhabi Emirate and comparisons with other populations.

BACKGROUND: Among all the polymorphic markers available to date, a hypervariable region located in the 3' of the human apolipoprotein B gene has been extensively studied in global populations throughout the world. PATIENTS AND METHODS: Using a polymerase chain reaction-based assay, we investigated the allele and genotype frequency distributions of the alleles (corresponding to repeats of a 30 base-pair core DNA sequence) of this hypervariable region in a group of 367 unrelated nationals (201 males, 166 females) from the United Arab Emirates. RESULTS: We found 18 different alleles, ranging from 21 to 55 repeats, making up 51 genotypes that occurred in Hardy-Weinberg proportions and were associated with a heterozygosity index of 80.9%. The allele frequency distribution was different from that of other populations in that it was trimodal, with peaks at 31, 37 and 47 repeats, with corresponding relative frequencies of 16.1%, 25.1% and 6.0%. A four-allele model, which allowed comparisons with other reports, revealed distribution differences with all other ethnic groups except South Asians and Serbs. CONCLUSION: This marker is very informative for the Emirati population, and will be very useful for UAE-specific DNA fingerprinting. It will also be a valuable tool for assessing the role of apolipoprotein B in cardiovascular diseases.

The angiotensin-converting enzyme (ACE) gene insertion/deletion dimorphism tracks with higher serum ace activities in both younger and older subjects.

BACKGROUND: The absence of a 287 base pair alu sequence in the ACE gene (D allele) is associated with higher ACE levels than its presence (I allele) in adults. We carried out a case-control study of the ACE*I/D dimorphism in relation to circulating ACE activities to evaluate associations between the two variables in adults, compared to younger (18 years or less) individuals. MATERIALS AND METHODS: Genotypes of the ACE*I/D dimorphism were determined on DNA samples from a population of 164 random (unrelated) Emirate nationals, composed of two groups: 112 subjects above 18 years of age (range=20-77 years), and 52 subjects of 18 years or less (range=1-18), and analyzed for putative associations with serum ACE activities. ACE*I/D genotypes of the 164 individuals were determined by assays based on polymerase chain reaction. ACE activities were determined on serum samples of these subjects by colorimetric assays. RESULTS: The D allele was associated with increased ACE values in both adult and younger individuals. Mean ACE activity levels associated with II, ID and DD genotypes, however, were 42%-61% higher in the 18 years and under group of subjects. The ACE*I/D marker accounted for 28% of the variance of the phenomenon determining ACE levels in adults, and for 30% among youngsters. CONCLUSION: The ACE*I/D dimorphism correlated strongly with circulating ACE activities in both adult and young Emirati subjects, and the corresponding mean ACE activities were significantly higher among the youngsters.

An analysis of skin prick test reactions in asthmatics in a hot climate and desert environment.

BACKGROUND: Studies have shown that allergens are very important sensitizing agents in patients with asthma. Respiratory disorders such as asthma and allergic rhinitis are common in the United Arab Emirates, (UAE). OBJECTIVES: The aim of this study was to investigate the relationship between allergen specific IgE antibodies and skin test reactivity in patients with asthma in hot climate and desert Arabian country. DESIGN: A hospital-based prospective study conducted. SETTING: Tawam Teaching Hospital, Al-Ain, UAE. PATIENTS: 327 adult patients recruited with respiratory, dermatologic and ophthalmologic diseases of suspected allergic origin who attended Tawam Teaching Hospital of Faculty of Medicine, Al Ain, UAE, during three years from 1996 to 1998. METHODS: Skin Prick Test (SPT) and radioallegosorbent tests (RAST) were performed on 327 patients for common allergens. The blood sample was taken for measuring specific IgE concentration. RESULTS: There were 327 UAE patients of whom 117 (35.8%) were males and 210 (64.2%) were females. The population sample had a higher prevalence of diagnosed asthma among females (48.1%) than in males (36.7%). Skin prick testing showed that 244 patients (74.6%) had positive results, and 83 patients (25.4%) were found to be skin test negative. 44% had a positive family history of asthma. The twelve most common reactions in the United Arab Emirates were: Mesquite (45.5%), Grass Mix (40.7%). Cottonwood (33.1%), Bermuda Grass (31.3%), Kochi (25.8%), Acacia (25.6%), Alfalfa (22.9%), Chenopodium (19.6%), Date palm (13.8%), Cockroach (14.7%), house dust (11.9) and Dust mite (9.5%). Total IgE level (> 100 kU/l) was strongly associated with history of wheeze (p = 0.019), asthma (p = 0.01) and allergic rhinitis (p < 0.0001), atopy (p < 0.0001) and the presence of specific IgE antibodies to grass pollen (p < 0.0001), mite (p = 0.008) and cockroaches (p = 0.025). CONCLUSION: The present study revealed that hypersensitivity to pollens, house dust, dust mite and cockroach was common. The family history, environment, and airborne allergens are identified to be risk factors for asthma and other allergic diseases in Arabian Gulf Countries.