[Unusual clinical presentation of cutaneous leishmaniasis in three diabetic patients]. / Leishmanioses cutanées d'aspect clinique inhabituel chez trois patients diabétiques.

INTRODUCTION: Cutaneous leishmaniasis (CL) is a parasitic infection characterized by significant clinical variability. Unusual and atypical clinical aspects of infection have been reported in immunodeficient patients or associated with particular parasite species. We report three cases of CL from foci of Leishmania major with a particular clinical presentation in diabetic patients. OBSERVATIONS: Patient 1: a 37-year-old man was admitted to the dermatology department for cutaneous vegetative ulcers spreading to the dorsal surface of the foot. History-taking revealed a stay in Er-Rachidia (East of Morocco, a known focus of CL L. major) six weeks earlier. Diabetes mellitus type I was discovered during hospitalization. The patient's 43-year-old sister (patient 2), diabetic for 6 years, consulted for a single leg ulcer appearing 3 months after the same trip to Er-Rachidia. Patient 3: a 61-year-old patient with a 7-year history of diabetes and under oral antidiabetics presented an extended vegetative lesion of the posterior surface of the leg 2 months after staying in Er-Rachidia. A diagnosis of CL was retained on the basis of epidemiology and history (living in an endemic areas of leishmaniasis), coupled in patients 1 and 3 with microbiological evidence involving identification of Leishmania bodies in skin smears or skin biopsies. All patients were treated with two intra-lesional injections per week of meglumine antimony (Glucantime(®)) for 6 weeks. The outcome was marked in all cases by healing of lesions and persistent pigmented scarring. DISCUSSION: We described three particular clinical aspect of CL emerging from a known focus of L. major, where infection is classically associated with vegetative or ulcero-vegetative lesions. This unusual profile suggests the role of factors related to parasite species and/or diabetes found in our three patients.

Iron repletion relocalizes hephaestin to a proximal basolateral compartment in polarized MDCK and Caco2 cells.

While intestinal cellular iron entry in vertebrates employs multiple routes including heme and non-heme routes, iron egress from these cells is exclusively channeled through the only known transporter, ferroportin. Reduced intestinal iron export in sex-linked anemia mice implicates hephaestin, a ferroxidase, in this process. Polarized cells are exposed to two distinct environments. Enterocytes contact the gut lumen via the apical surface of the cell, and through the basolateral surface, to the body. Previous studies indicate both local and systemic control of iron uptake. We hypothesized that differences in iron availability at the apical and/or basolateral surface may modulate iron uptake via cellular localization of hephaestin. We therefore characterized the localization of hephaestin in two models of polarized epithelial cell lines, MDCK and Caco2, with varying iron availability at the apical and basolateral surfaces. Our results indicate that hephaestin is expressed in a supra-nuclear compartment in non-polarized cells regardless of the iron status of the cells and in iron deficient and polarized cells. In polarized cells, we found that both apical (as FeSO(4)) and basolateral iron (as the ratio of apo-transferrin to holo-transferrin) affect mobilization of hephaestin from the supra-nuclear compartment. We find that the presence of apical iron is essential for relocalization of hephaestin to a cellular compartment in close proximity but not overlapping with the basolateral surface. Surface biotinylation studies indicate that hephaestin in the peri-basolateral location is accessible to the extra-cellular environment. These results support the hypothesis that hephaestin is involved in iron mobilization of iron from the intestine to circulation.

[Fatal erythroderma in a young Moroccan]. / Erythrodermie fatale chez un jeune marocain.

The purpose of this report is to describe a case involving a young Moroccan who abruptly developed pruritic papulo-vesicular lesions with erythroderma. Secondary development of jaundice and tumoral syndrome lead to diagnosis of an acute form of adult T-cell leukemia/lymphoma associated with HTLV-1 infection. The patient died within three months. To o ur knowledge, this is the first such case reported in Morocco.

[Maxillary bone sarcoidosis]. / Sarcoïdose osseuse maxillaire.

INTRODUCTION: Sarcoidosis is an unexplained systemic granulomatosis. Bone localizations of the disease are rare. We report a maxillary localization. CASE: A 35-year-old patient consulted for facial dysmorphia first observed 2 years before. This swelling was associated to nodular panniculitis lesions and xerostomia. The facial asymmetry was due to maxillary gingival and alveolar swelling. It was associated with scarring in the legs and a purple nodular facial lesion. Lip and jaw biopsies revealed epithelioid and giant cell granulomas without caseous necrosis. The panoramic dental X-ray showed diffuse horizontal alveolar ridge lysis and CT scan revealed an osteolytic lesion of the right maxilla associated to a bone-condensing lesion of the left hemi-mandible. DISCUSSION: The diagnosis of sarcoidosis is made in case of epithelioid and giant cell granulomas without caseous necrosis and the ruling out of other possible diagnoses, including tuberculosis. Bone involvement is rare; face and maxillary localization are extremely rare. The recommended treatment is corticosteroids. Facial remodeling surgery is not recommended.

[Stevens-Johnson and Lyell syndromes: mucocutaneous and ocular sequels in 43 cases]. / Séquelles cutanéomuqueuses et oculaires des SJS et de Lyell.

INTRODUCTION: The ophthalmic sequelae of Stevens-Johnson and Lyell syndromes are deemed serious, and their mucocutaneous syndromes can adversely affect social and functional outcomes. The aim of this study is to describe these sequelae in Morocco. METHODS: This retrospective study involved all patients hospitalized in the dermatology department of the Ibn Rochd University Hospital in Casablanca for toxic epidermal necrolysis or Stevens-Johnson syndrome (SJS). The study period lasted from January 1986 to December 2006. Mucosal, cutaneous and ocular sequelae of these diseases were identified during follow-up. RESULTS: During this 21-year period, 43 cases of Lyell syndrome and SJS were analyzed. Twenty-five women and 18 men were included and the average age was 28 years. Clinical forms were as follow: Lyell's syndrome: 32 cases; SJS: six cases; intermediary Lyell-SJS form: five cases. Average follow-up was 3 years. Concerning mucocutaneous sequelae, 72% of patients had diffuse hyperchromic macules with scarring, photosensitivity was noted in 70% of cases, telogen effluvium was seen in 10 cases, abnormal sweating was noted in eight cases, nail loss was seen in eight cases, and vaginal bands were noted in two cases. In the chronic phase, 70% of patients had photophobia with chronic lacrimation. Eyelid malposition was noted in 21% of cases: ectropion (n=6), entropion with trichiasis (n=3) and symblepharon in 13 cases (30%). Corneal complications involving superficial punctate keratitis were noted in 42% of cases and were associated with corneal neovascularisation in five cases. Finally, bilateral dry eye syndrome was seen in 24 cases (56%). CONCLUSION: Our study confirms the reality of ocular, and mucocutaneous sequelae of Stevens-Johnson and Lyell syndromes. Ocular sequelae are dramatic, while cutaneous sequelae are unsightly. These sequelae have marked repercussions on the social and professional integration of our patients, most of whom were young.

[Suppurations of the perineal and gluteal region: An aetiological study of 60 cases]. / Suppurations périnéofessières : étude étiologique de 60 cas.

BACKGROUND: The gluteal region is a complex area of the body that may be the seat of several diseases with dermatological manifestations. The purpose of this series was to study the aetiological profile of suppurative lesions of the gluteal region in patients in Morocco. PATIENTS AND METHODS: A retrospective study was carried out on patients presenting suppuration of the gluteal region hospitalised in our department between 1987 and 2008. The epidemiological, clinical and aetiological data for 60 cases were reviewed. Skin biopsies with bacterial, fungal and histological studies, as well as bacterial and fungal cultures of pus and anorectal examination, were performed for all patients. RESULTS: We examined the files for 44 males and 16 females; mean age was 44 years (range: 13 to 70 years) and the average duration of illness was 6.5 years. The various aetiologies were as follows: hidradenitis suppurativa (27 cases), cutaneous tuberculosis (10 cases), Crohn's disease (nine cases), phlegmon-carbuncle (eight cases), tumours (four cases) and deep mycosis (two cases). Medical and surgical treatments were aetiological. DISCUSSION: There are various aetiologies of suppurations of the gluteal region. In Morocco, hidradenitis suppurativa, cutaneous tuberculosis and Crohn's disease are the most frequent causes. Multidisciplinary management is essential.

Identification of zyklopen, a new member of the vertebrate multicopper ferroxidase family, and characterization in rodents and human cells.

We previously detected a membrane-bound, copper-containing oxidase that may be involved in iron efflux in BeWo cells, a human placental cell line. We have now identified a gene encoding a predicted multicopper ferroxidase (MCF) with a putative C-terminal membrane-spanning sequence and high sequence identity to hephaestin (Heph) and ceruloplasmin (Cp), the other known vertebrate MCF. Molecular modeling revealed conservation of all type I, II, and III copper-binding sites as well as a putative iron-binding site. Protein expression was observed in multiple diverse mouse tissues, including placenta and mammary gland, and the expression pattern was distinct from that of Cp and Heph. The protein possessed ferroxidase activity, and protein levels decreased in cellular copper deficiency. Knockdown with small interfering RNA in BeWo cells indicates that this gene represents the previously detected oxidase. We propose calling this new member of the MCF family "zyklopen."

Decreased hephaestin expression and activity leads to decreased iron efflux from differentiated Caco2 cells.

Iron is transported across intestinal brush border cells into the circulation in at least two distinct steps. Iron can enter the enterocyte via the apical surface through several paths. However, iron egress from the basolateral side of enterocytes converges on a single export pathway requiring the iron transporter, ferroportin1, and hephaestin, a ferroxidase. Copper deficiency leads to reduced hephaestin protein expression and activity in mouse enterocytes and intestinal cell lines. We tested the effect of copper deficiency on differentiated Caco2 cells grown in transwells and found decreased hephaestin protein expression and activity as well as reduced ferroportin1 protein levels. Furthermore, the decrease in hephaestin levels correlates with a decrease of (55)Fe release from the basolateral side of Caco2 cells. Presence of ceruloplasmin, apo-transferrin or holo-transferrin did not significantly alter the results observed. Repletion of copper in Caco2 cells leads to reconstitution of hephaestin protein expression, activity, and transepithelial iron transport.

[Primary erythermalgia: efficacy of oxcarbazepine]. / Erythermalgie primitive: efficacité de l'oxcarbazépine.

BACKGROUND: Essential erythermalgia is a rare acrosyndrome that is difficult to treat. Herein, we report a new case unusual in terms of both the associated partial epileptic seizures and of the favourable outcome achieved through antiepileptic treatment with oxcarbazepine. PATIENTS AND METHODS: A male adolescent born of a non-consanguineous marriage had been followed since the age of 5 years for essential erythermalgia. A number of different treatments had been tried in succession but without success: beta blockers, acetylsalicylic acid, paracetamol and indomethacin. At the age of 15 years, the patient presented serious depression requiring antidepressant therapy with sertraline. Seven days after the start of this medication, the patient presented temporal partial epileptic seizures confirmed by electroencephalogram. The antidepressant was stopped and a new-generation antiepileptic, oxcarbazepine, was instituted. The epileptic seizures subsided and so too did the paroxysmal pain associated with erythermalgia, in addition to which the patient's skin lesions improved. This therapeutic efficacy has persisted for 21 months. DISCUSSION: The novelty of this case report concerns the association of essential erythermalgia and epilepsy and the favourable outcome achieved with antiepileptic therapy. It may well be that the patient's erythermalgia and epilepsy were both responsive to sodium channel therapy, as described with gene SCN9A disorders; however, this point could not be checked in the present case. In practice, we feel there are grounds for use of oxcarbazepine as an alternative treatment in the management of essential erythermalgia.

Age-related changes in iron homeostasis in mouse ferroxidase mutants.

Disorders of iron metabolism are a significant problem primarily in young and old populations. In this study, We compared 1-year-old C57BL6/J mice on iron deficient, iron overload, or iron sufficient diets with two similarly aged genetic models of disturbed iron homeostasis, the sla (sex-linked anemia), and the ceruloplasmin knockout mice (Cp(-/-)) on iron sufficient diet. We found tissue specific changes in sla and nutritional iron deficiency including decreased liver Hamp1 expression and increased protein expression of the enterocyte basolateral iron transport components, hephaestin and ferroportin. In contrast, the Cp(-/-) mice did not show significantly increased Hamp1 expression despite increased liver iron suggesting that regulation is independent of liver iron levels. Together, these results suggest that older mice have a distinct response to alterations in iron metabolism and that age must be considered in future studies of iron metabolism.

Evaluation of the effectiveness of a broad-spectrum sunscreen in the prevention of chloasma in pregnant women.

BACKGROUND: Chloasma, or melasma, is a pigmentary disorder that can affect between 50% and 70% of pregnant women. During pregnancy, chloasma does not require any particular treatment beside the use of an effective sunscreen and avoiding the use of any photosensitizing products or inappropriate skin care routine. However, there exist very few studies related to the benefits of sunscreens to prevent this dermatosis. OBJECTIVE: The aim of this study was to assess the role of a broad-spectrum sunscreen in the prevention and treatment of chloasma in pregnant women. METHODS: We tested the effectiveness and tolerance of a sunscreen composition (SPF 50+, UVA-PF 28) during a 12-month clinical trial on 200 parturients. RESULTS: The 'excellent' tolerance of the sunscreen under evaluation was confirmed. Out of 185 patients who completed the study, only five new cases of chloasma were noted, an occurrence of 2.7%, which is much lower than the 53% previously observed in an usual condition study (same investigators, same geographical area and same time frame). In addition, the clinical effectiveness of the evaluated sunscreen was judged 'excellent' by the majority of parturients and by the research dermatologists during all the consultations. It is also worth noting that at 6 months, a clinical improvement was observed in 8 out of 12 volunteers who were affected by a pre-existing chloasma observed during their inclusion visit. Colorimetric measurements showed that, at the end of their pregnancy, the parturients' skin was, on average, significantly lightened (increase of parameter L* in 38% cases) and less pigmented (reduction of parameter b* in 50% cases); thus, resulting in a significantly lighter skin colour (increase of ITA degrees in 69% cases) compared to their inclusion visit. CONCLUSIONS: This study clearly demonstrates the effectiveness of the well-tolerated broad-spectrum sunscreen evaluated, in the prevention of the development of chloasma in pregnant women.

[Terbinafine-induced Stevens-Johnson syndrome and aggravation of systemic lupus erythematosus]. / Syndrome de Stevens-Johnson et aggravation d'un lupus systémique induits par la terbinafine.

BACKGROUND: There have been published reports of induction and aggravation of subacute systemic lupus erythematosus of lupus by terbinafine. We report the case of female patient with systemic lupus erythematosus who, after treatment with terbinafine, presented a Stevens Johnson syndrome eruption, together with renal exacerbation of her connective tissue disease. OBSERVATION: A 25 - year-old woman was followed for 4 years for systemic lupus erythematosus was no renal involvement. The patient was stable under corticosteroids (20 mg/d) and chloroquine (200 mg/d). She was treated with terbinafine onychomycosis caused by Trichophyton rubrum. Seven days after trunk and limbs, with cheilitis affecting the mucous membrane and bilateral conjunctivitis. This rash was followed by epidermolysis involving 10% of the cutaneous area. Stevens-Johnson syndrome was diagnosed. Laboratory tests indicated massive hematuria and proteinuria, and the renal needle biopsy sample showed signs of class III lupus glomerulonephritis. The anti-histone antibodies were highly positive. The patient was treated with systemic corticosteroids (1 mg/kg/d), chloroquine was recommenced and cyclophosphamides were given in a bolus. The outcome of the patient's eruption and lupus was favorable. DISCUSSION: Although induction and worsening of lupus by terbinafine have already been reported, the present case differs through the concomitant occurrence of eruption on treatment with terbinafine and severe relapse of lupus, thus suggesting the involvement of a shared immunological mechanism.

[Childhood cutaneous tuberculosis from Morocco: a study of 30 cases]. / Tuberculose cutanée de l'enfant au Maroc: étude de 30 cas.

UNLABELLED: In Morocco, tuberculosis is still endemic. Cutaneous tuberculosis is ranged the fifth after the pleuro-pulmonary, lymphe node, urogenital and digestive tuberculosis. It mainly affects young people. Few studies of cutaneous tuberculosis are available in this age group. The aim of our study is to emphasize its epidemiological features. PATIENTS AND METHODS: It is a retrospective study including all cases of childhood cutaneous tuberculosis observed between January 1981 and December 2004. The diagnosis was based on the confrontation of clinical, immunological, bacteriological and histological data. RESULTS: Thirty cases were collected. The mean age was 11 years. The clinical features are as follows: gumma 46.6%, scrofuloderma 36.6%, lupus vulgaris 13.3% and skin tuberculosis chancre 3.3%. The Mantoux test was positive in 67%, tuberculoid granuloma was observed in 78% and the search of Mycobacterium tuberculosis was positive in 13%. DISCUSSION: Gumma and scrofuloderma were the most frequent forms as in other Moroccan series. These results attest the endemicity of this affection in our country. The diagnosis relies on the discovery of Mycobacterium tuberculosis; as this situation is rare for the cutaneous location, the diagnosis relies then on the association of clinical and paraclinical criteria.

[Precocious mediastinal lipomatosis: a rare complication of systemic corticosteroid therapy]. / Lipomatose médiastinale précoce: une complication exceptionnelle de la corticothérapie generale.

BACKGROUND: Corticosteroid-induced lipomatosis results from hypertrophy within adipose tissue; the condition is frequently asymptomatic and its incidence is underestimated. We report a case of mediastinal lipomatosis that is rare in terms of both site and presenting symptoms. CASE REPORT: A 46-year-old woman with no disease history other than obesity with a weight of 90 kg had been treated since 2002 for mixed connective tissue disease (profound lupus and dermatomyositis). She had been treated with oral corti costeroids (1 mg/kg/d). Two months after the start of treatment, she presented chest pains, resting dyspnea particularly aggravated in dorsal decubitus, chest edema in the subclavicular space and jugular turgescence. Chest x-ray revealed widening of all levels of the mediastinum. The chest CT scan showed lipomatosis throughout the entire mediastinum with no associated chest abnormalities or pericardial effusion. Rapid downward dosage adjustment ofcorticosteroids to 10 mg/d coupled with synthetic antimalarials resulted in gradual reduction of symptoms. The chest scan performed two months later short stabilization of the patient's mediastinal lipomatosis. DISCUSSION: The effects of long-term of glucocorticosteroid therapy are well-known, in particular Cushing's syndrome. Lipomatosis has been described more recently and affects different axial regions. Mediastinal localization is seen in 15% of patients treated. This presentation is less common than orbital and epidural localizations. Although often asymptomatic, as in our own report, it may present with worrying symptoms that pose real diagnostic problems. The diagnostic examinations of choice are CT scan or MRI. Regression following discontinuation or reduction of corticosteroids is inconsistent and often gradual.

Decreased hephaestin activity in the intestine of copper-deficient mice causes systemic iron deficiency.

Copper and iron metabolism intersect in mammals. Copper deficiency simultaneously leads to decreased iron levels in some tissues and iron deficiency anemia, whereas it results in iron overload in other tissues such as the intestine and liver. The copper requirement of the multicopper ferroxidases hephaestin and ceruloplasmin likely explains this link between copper and iron homeostasis in mammals. We investigated the effect of in vivo and in vitro copper deficiency on hephaestin (Heph) expression and activity. C57BL/6J mice were separated into 2 groups on the day of parturition. One group was fed a copper-deficient diet and another was fed a control diet for 6 wk. Copper-deficient mice had significantly lower hephaestin and ceruloplasmin (approximately 50% of controls) ferroxidase activity. Liver hepcidin expression was significantly downregulated by copper deficiency (approximately 60% of controls), and enterocyte mRNA and protein levels of ferroportin1 were increased to 2.5 and 10 times, respectively, relative to controls, by copper deficiency, indicating a systemic iron deficiency in the copper-deficient mice. Interestingly, hephaestin protein levels were significantly decreased to approximately 40% of control, suggesting that decreased enterocyte copper content leads to decreased hephaestin synthesis and/or stability. We also examined the effect of copper deficiency on hephaestin in vitro in the HT29 cell line and found dramatically decreased hephaestin synthesis and activity. Both in vivo and in vitro studies indicate that copper is required for the proper processing and/or stability of hephaestin.