[Diagnosis and treatment of leprous neuropathy in practice]. / Diagnostic et traitement de la neuropathie lépreuse en pratique.

Leprosy still affects 240,000 persons every year in the world. It is a particularly common cause of neuropathy and severe disabilities in developing countries. With increasing migration, new cases of leprosy are regularly diagnosed in developed countries, where it still remains rare and so underestimated. Cutaneo-nevritic leprosy is the most frequent form of leprosy. It may be diagnosed by the clinical features and the cutaneous histology and bacteriology. Neuritic leprosy without obvious skin lesions is reported in 5 to 15% of leprosy patients. It must be suspected in persons from areas of endemic disease presenting with nerve thickening and associated nerve deficit. Nerve biopsy is essential for diagnosis. However search for bacilli in cutaneous samples may be of great help and avoid nerve biopsy. Acute and severe neuritis occurs during reactional states, reversal reaction (Type 1) and erythema nodosum leprosum (Type 2). Multidrug therapy is advocated. The treatment of acute neuropathy needs a supplementary medical and sometimes surgical treatment.

[Myeloproliferative hypereosinophilic syndrome revealed by bipolar mucosal ulcerations]. / Syndrome hyperéosinophilique d'origine myéloproliférative révélé par des ulcérations muqueuses bipolaires.

BACKGROUND: Hypereosinophilic syndrome (HES) is defined as an eosinophil count equal to or greater than 1.5 G/L for more than 6 months with organ damage (heart, nervous system, lung, etc) after the exclusion of other common causes of eosinophilia. A myeloproliferative variant of HES with FIP1L1-PDGFRα fusion gene inducing constitutive activation of a tyrosine kinase receptor has been characterized. We report a case in which the diagnosis was revealed by mucosal erosions and ulcerations. PATIENTS AND METHODS: A 50-year-old man reported bipolar erosions. He presented with an erosion on the glans, an ulceration on the lower lip and mild dermographism. He had an eosinophil count of 7.5 G/L (n<0.7) and raised LDH at 520 IU/L (n<480). Screening for the usual causes of eosinophilia was negative. Histology of the labial ulceration showed a polymorphous inflammatory infiltrate containing eosinophils. A chest scan demonstrated a ground glass-like pulmonary infiltrate and broncho-alveolar lavage revealed eosinophilic alveolitis. The myelogram showed rich bone marrow with eosinophils. FIP1L1-PDGFRα fusion transcript was detected in the blood. Imatinib (Glivec(®)) was initiated and a favourable outcome was achieved within a few months and maintained after one year of treatment. DISCUSSION: Cutaneous signs are frequent features of HES. They are polymorphous and include pruritis, erythematous rash and urticaria. Mucosal ulcerations are uncommon and appear more frequently with the myeloproliferative FIP1L1-PDGFRα-associated variant of HES. Early diagnosis allows the onset of a targeted treatment with imatinib that may prevent the apparition of organ damage.

[Gastric sarcoidosis revealed by cutaneous follicular sarcoidosis]. / Sarcoïdose gastrique révélée par une sarcoïdose cutanée folliculaire.

BACKGROUND: Sarcoidosis is a disease well known to dermatologists because of the frequency of cutaneous involvement. Routine screening is performed for involvement of the lungs, lymph nodes, eyes, liver and heart. However, gastro-intestinal sarcoidosis is both rare and frequently silent, and it thus often goes undiagnosed. We report the case of a Caribbean woman whose cutaneous lesions allowed a posteriori diagnosis to be made of gastric sarcoidosis. PATIENTS AND METHODS: A 45-year-old Caribbean woman consulted for diffuse erythematous or hypochromic, squamous and follicular micropapular lesions associated with inflammatory rheumatoid arthritis. Clinical examination and laboratory data led to a diagnosis of cutaneous sarcoidosis. It was later discovered that she had presented epigastric pains a few months earlier and that she had undergone gastroscopy and gastric biopsies. Histopathology had revealed non-caseating epithelioid-cell granulomas with giant cells, but no further exams were performed. The patient was diagnosed a posteriori with cutaneous-articular and gastric sarcoidosis. DISCUSSION: In contrast with hepatic involvement, which is frequent and well-known, sarcoidosis affecting the gastro-intestinal tract is rare and poorly known. This form of the disease is frequently clinically silent and is thus probably under-reported. The stomach is the site most frequently affected. Gastric sarcoidosis is seen in some 10% of patients with systemic sarcoidosis and is symptomatic in less than 1% of cases. It is important to diagnose these forms since they may be associated with a certain degree of morbidity.

[Bilateral inguinal lymphadenopathy and erythema nodosum: an uncommon presentation of cat scratch disease]. / Adénopathies inguinales bilatérales et érythème noueux: une présentation originale de la maladie des griffes du chat.

Cat scratch disease is usually revealed by a proximal lymphadenopathy related to the inoculation site. We report a 22-year-old female who presented with erythema nodosum and bilateral inguinal lymphadenopathy. Serologic test and lymph node PCR detection for Bartonella henselae were negative. Nevertheless, the patient received doxycycline and clinical manifestations rapidly resolved. A follow-up detection of IgM and IgG against Bartonella henselae performed 1 month later was positive. This case report illustrates an original presentation of cat scratch disease and reminds us the lack of sensitivity of laboratory investigations.

[Leprosy in children: A diagnosis that must not be missed]. / Lèpre de l'enfant : un diagnostic à ne pas méconnaître.

BACKGROUND: With 254,525 new cases reported in 2007, leprosy is the worlds' second most widespread form of mycobacteriosis. According to the WHO, eradication of leprosy as a public health problem (defined by less than one case per 10,000 people) has been globally achieved. High endemic zones, however, still subsist. Leprosy rates among children, which reflect a country's endemic level, ranged from 0.55 to 19.2 % in 2006. Due to world population migrations, cases of leprosy are now seen in mainland France, in both children and adults. PATIENTS AND METHODS: We describe three leprosy patients aged under 15 years treated at the Dermatology Unit of Saint Louis Hospital between 1st January 2002 and 31st December 2008. The three cases described account for 3 % of new patients treated for leprosy at Saint Louis Hospital over this 7-year period. All were born in an endemic country. Lesions appeared 18 months after arrival in France in two cases and clinical diagnosis was made in only one case. Due to absence of sensory loss in the lesions, diagnosis was reliant upon histopathological examination in two cases. CONCLUSION: Leprosy should be suspected in children from endemic countries presenting skin lesions, particularly hypochromic lesions, even if there is no sensory loss, regardless of how long they have been living in France.

[Pneumatosis cystoides intestinalis complicating paraneoplastic dermatomyositis]. / Pneumatose kystique intestinale compliquant une dermatomyosite paranéoplasique.

BACKGROUND: Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by the presence of gas-filled cysts within the wall of the digestive tract. Classically, it occurs in lung or colon diseases but rarely in patients with collagen disorders. We report a new case of PCI occurring during the course of paraneoplastic dermatomyositis. PATIENTS AND METHODS: A 53-year-old woman was diagnosed with dermatomyositis two years ago. Relapse of dermatomyositis preceded the discovery of metastases for which chemotherapy was initiated with 5-fluorouracil and vinorelbine. Three months later, she was admitted to our department for abdominal pains. On physical examination, the abdomen was distended with normal peristalsis. There was no evidence in favour of active dermatomyositis. Abdominal computed tomography scan showed gas collection in the mesentery, revealing the PCI. There was also pneumoperitoneum. The patient slowly improved with symptomatic treatment. DISCUSSION: PCI is uncommon in systemic diseases and extremely rare in dermatomyositis. The pathogenesis and aetiology of PCI are unknown in most cases. In collagen diseases, several hypotheses have been suggested: digestive hypokinesia, corticosteroid-induced ulceration and intestinal vasculitis. In our patient, two factors contributed to PCI: corticosteroid administration and a chemotherapeutic agent (vinorelbine), resulting in severe constipation. Diagnosis of PCI is based on abdominal computed tomography. Pneumoperitonitis is frequent. Although rare, the diagnosis of PCI must be evoked in collagen disorder patients presenting nonspecific abdominal symptoms.

[Sensory-motor neuropathy: a slow and misleading case of leprosy]. / Neuropathie périphérique sensitivomotrice : une forme lente et trompeuse de maladie de Hansen.

The diagnostic process of sensory-motor neuropathies is difficult. Atypical variants and rare etiologies also contribute to delay the diagnosis. We report the case of a 70-year-old woman with slowly progressive asymmetric axonal sensory-motor neuropathy. Leprosy was identified after an eight-year delay. Nerve biopsy was required to establish the diagnosis: electron microscopy revealed debris of Hansen's bacillus in the nerve. Treatment was fully curative after several months. Leprosy is a rare cause of neuropathy in Europeans. Systematic inquiry about travel to endemic areas would be helpful in establishing the diagnosis. In such cases, nerve biopsy is crucial.

[Polyarthritis and papular eruption revealing leprosy]. / Polyarthrite et éruption papuleuse révélant une lèpre.

Leprosy is generally revealed by cutaneous lesions often associated to nerve impairment. Rarely, it may be revealed by polyarthritis. The diagnosis, often delayed in the cutaneous-nevritic form because of the low prevalence of the disease in metropolitan France, is very difficult in case of rheumatic presentation. We report the case of a 28 year-old woman from Mali, who was diagnosed with lepromatous borderline leprosy with reversal reaction occurring in the postpartum as she presented with polyarthritis and skin lesions.

[Erysipelas-like dermatitis of the legs revealing aspergilloma of the maxillary sinus]. / Dermatite érysipéloïde des membres inférieurs révélant un aspergillome du sinus maxillaire.

BACKGROUND: Skin signs is associated with Aspergillus are rare and are seen principally in immunodepressed patients. Distinction is generally made between primary skin aspergillosis, caused by direct cutaneous inoculation with the offending organism, and secondary skin aspergillosis, associated with peripheral emboli from an area of chronic pulmonary or sinus mycetoma. There have been rare reports of indirect satellite skin signs resulting from Aspergillus infection, and below we present such a case. PATIENTS AND METHODS: A 40 year-old immunocompetent man consulted for erysipeloid plaques on the lower limbs recurring over a period of seven months. X-rays and CAT scans of the sinus demonstrated asymptomatic axillary sinusitis probably caused by Aspergillus. The diagnosis was confirmed by surgery, which resulted in cure without additional antifungal treatment. The inflammatory syndrome subsided and after 15 months, there was no recurrence of lesions. DISCUSSION: The absence of relapse following treatment of the focus of aspergillosis forms a major argument in favour of a causal relationship between the erysipeloid dermatitis and the sinus mycotic infection. The hypothesis of a septic embologenic mechanism within the sinus was abandoned in favour of a mechanism similar to streptococcal nodular erythema, seen in diseases involving immune complexes, possibly caused by allergy to Aspergillus proteins. This case history demonstrates the existence of satellite skin signs of Aspergillus infection indicative of neither primary nor secondary aspergillosis.

[Pentoxifylline in the treatment of erythema nodosum leprosum: results of an open study]. / Efficacité de la pentoxifylline dans le traitement de l'érythème noueux lépreux: résultats d'une étude ouverte.

Erythema nodosum leprosum (ENL) is a well-known immunological serious complication affecting lepromatous multibacillary leprosy patients. For a long time, ENL has been regarded as an immune complex-mediated disease or Arthus phenomenon. Recently, it has been reported that ENL was associated with high serum tumor necrosis factor-alpha (TNFa) levels, suggesting that this cytokine could also play a central role in the manifestations of ENL. Thalidomide (TH) and systemic steroids (S), both TNFa production inhibitors, are the two current effective drugs for the management of ENL. However, TH is rarely available in leprosy endemic countries, and its teratogenicity and neurotoxicity strongly limit its use. Moreover, the morbidity of S and the frequent steroid-dependence of ENL also create real therapeutic problems. Recently, the efficacy of pentoxifylline (PTX), which also inhibits in vitro and in vivo production of TNFa, has been suggested for ENL treatment. We report our experience on its use for the treatment of 15 leprosy patients suffering from a first ENL. attack. (11 cases), a chronic steroid-dependent ENL (3 cases) or chronic steroid- and thalidomide-dependent ENL (1 case). PTX has been given at 800 mg t.i.d, (2 cases) or 400 mg t.i.d. (13 cases) doses. The patients received PTX at the initiating dosage until complete clinical cure. At the end of ENL attacks, PTX was either abruptly stopped or tapered down over the next 4 months. In ten of 11 patients who developed ENL for the first time, the systemic symptoms and neuritic pains disappeared within one week; at three weeks, half of the patients were cured and the other half had striking clinical improvement; complete cure was obtained within 7 to 35 days (mean: 27 days). A relapse occurred within 2-3 months in the 5 patients, in which PTX was abruptly stopped. In contrast, no relapse occurred in the patients who benefited from decreasing doses of PTX. Recurrent ENL episodes also responded well to PTX. The 3 patients who had chronic steroid-dependent ENL failed to show any improvement after 3 to 6 weeks of PTX. In contrast, steroid therapy could be stopped in the steroid- and thalidomide-dependent patient. Our results confirm the action of PTX if it is slowly tapered down (4 months seem sufficient) and not abruptly to avoid relapses. As it is safe use, PTX could constitute the first line of ENL attack treatment.

[Cutaneous lupus erythematosus following argon laser treatment]. / Lupus érythémateux cutané déclenché par le laser argon.

BACKGROUND: It is well known that exposure to ultraviolet light can trigger lupus manifestations. Other light sources may have the same effect. We report a case of argon laser-induced lupus erythematosus. CASE REPORT: A 59-year-old women developed an erythematous edematous infiltrated and sensitive lesion over the right cheek ten days after an argon laser treatment of the retina. The lesion spread towards the chin despite antibiotic treatment. Histology examination of a biopsy specimen and direct immunofluorescence suggested the diagnosis of cutaneous lupus erythematosus. The lesions regressed in one month with hydroxychloroquine (400 mg/d) treatment. DISCUSSION: Our patient developed argon laser induced cutaneous lupus erythematosus. It is known that ultraviolet light and non-ultraviolet frequencies (x-rays, visible light) can induce lupus manifestations. One case of discoid lupus erythematosus after argon laser has been reported. In our case, due to a technical error the laser beam was directed onto the ipsilateral cheek during the laser treatment of the retina. The low-energy beams used in ophthalmology would explain the absence of local burn but would be sufficient to trigger lupus. This case demonstrates that argon laser, a visible blue or green beam, can provoke cutaneous lupus erythematosus even if there is no heat-induced burn. It is important to be aware of this adverse effect due to the widespread use of lasers in dermatology, particularly for the treatment of cutaneous lupus lesions.

[Erythema annulare centrifugum and relapsing polychondritis]. / Dermatose à type d'érythème annulaire centrifuge et polychondrite atrophiante.

BACKGROUND: Relapsing polychondritis is a rare systemic disease. Skin involvement occurs in 20 to 50 % of cases. Cutaneous signs are most often related to a leukocytoclastic vasculitis. Association of relapsing polychondritis with neutrophilic dermatosis have also been reported. We report the first case of an erythema annulare centrifugum-like dermatosis associated with relapsing polychondritis, with a two years delay between both conditions. CASE REPORT: A 74 year-old man was seen for papulo-erythematous centrifugal annular lesions that appeared 18 months earlier in a context of bad general conditions. Biological tests were normal. Several skin biopsies were performed, showing at the beginning features of drug reaction and then of lupus-lichen. Treatment with hydroxychloroquine, topical corticosteroids, dapsone and thalidomide were unsuccessful. In the following months, the patient developed fever and relapsing bronchitis. Suddenly, a chondritis of the ears appeared, leading to the diagnosis of relapsing polychondritis. All the cutaneous, chondritic and respiratory signs disappeared with oral steroid therapy. Two years after the diagnosis of relapsing polychondritis the patient developed refractory anemia. DISCUSSION: Cutaneous signs of relapsing polychondritis are frequent and may occur several months or years before the chondritis. They are polymorphous, but to the best of our knowledge, a clinical aspect of erythema annulare centrifugum has never been described. Our observation recalls the sometimes long delay between the cutaneous and the chondritic signs of relapsing polychondritis and the high frequency of dysmyelopoiesis in relapsing polychondritis with cutaneous involvement.

Comparison of the T cell patterns in leprous and cutaneous sarcoid granulomas. Presence of Valpha24-invariant natural killer T cells in T-cell-reactive leprosy together with a highly biased T cell receptor Valpha repertoire.

The T-cell-reactive (eg, tuberculoid and reversal) forms of leprosy represent a well-defined granulomatous reaction pattern against an invading pathogen. The immune response in cutaneous sarcoidosis is a granulomatous condition that pathologically is very similar to T-cell reactive leprosy. However, it lacks a defined causative agent. In view of the role of NKT cells in murine granulomas induced by mycobacterial cell walls, we have searched for the presence of NKT cells in the cutaneous lesions of both leprosy and sarcoidosis. These cells were present in T-cell-reactive leprosy but were undetectable in cutaneous sarcoidosis. We have also studied the TCR Valpha repertoire in the two diseases. In addition to Valpha24(+) NKT cells, all patients with T-cell-reactive leprosy showed a very restricted T-cell-reactive Valpha repertoire with a strong bias toward the use of the Valpha6 and Valpha14 segments. Valpha6 and Valpha14(+) T cells were polyclonal in terms of CDR3 length and Jalpha usage. In contrast, most sarcoidosis patients showed a diverse usage of Valpha chains associated with clonal or oligoclonal expansions reminiscent of antigen-driven activation of conventional T cells. Thus the origin and perpetuation of the two kinds of granulomatous lesions appear to depend on altogether distinct T-cell recruiting mechanisms.

[Thalidomide and thrombosis]. / Thalidomide et thromboses.

BACKGROUND: Teratogenicity and neuropathy are the well known serious side effects induced by thalidomide. We describe 5 cases of thrombotic events occurring within a brief delay after the onset of thalidomide in a manner that suggests that thalidomide could have acted as a precipiting or as a starting factor in these events. OBSERVATIONS: Five patients including 4 patients with lupus erythematosus (1 discoid lupus, 1 subacute lupus and 2 systemic lupus erythematosus) and one patient with a severe atopic dermatitis, all without previous history of vascular events, developed an arterial thrombosis (2 cases) or a venous thrombosis (3 cases), severe in 4 cases, few days or weeks after the onset of thalidomide treatment (50 to 100 mg daily). DISCUSSION: All the patients had risk factors of thrombosis: the presence of antiphospholipids and/or anticardiolipin antibodies in lupus erythematosus patients and a trauma in the atopic case. However the absence of a previous story of thrombosis, its rapid occurrence after the onset of thalidomide and its severity are intriguing. In addition, recent studies demonstrate that thalidomide has various effects that would act, among other things, on angiogenesis. Thus, we think that a doubt exists on a negative effect of thalidomide in thrombosis risk factors patients and that this hypothesis has to be confirmed.

No evidence for a role of human herpesvirus type 8 in sarcoidosis: molecular and serological analysis.

The aim of this study was to analyse the association between human herpesvirus type 8 (HHV8) and sarcoidosis. Using nested polymerase chain reaction (PCR), we tested the presence of HHV8 DNA sequences in 13 skin specimens and peripheral blood mononuclear cells from eight patients suffering from sarcoidosis. We also looked for the presence of HHV8 antibodies in the sera of 28 patients with sarcoidosis using three techniques: two indirect immunofluorescence assays and an enzyme-linked immunosorbent assay with recombinant capsid protein fragment encoded by open-reading frame 65. HHV8 PCR analysis was negative while HHV8 serological studies showed an overall prevalence of 18% among patients suffering from sarcoidosis: 43% in patients from sub-Saharan Africa, 17% in patients from Northern Africa, 12.5% in patients from the French West Indies and 0% in French patients. In conclusion, our results do not indicate an association between HHV8 and sarcoidosis but reflect the seroepidemiology of this virus in different geographical regions.

Subepidermal autoimmune bullous skin diseases associated with B-cell lymphoproliferative disorders.

The development of several types of autoimmune disorders is well known in the course of B-cell lymphoproliferative diseases. In order to investigate whether these autoimmune diseases may target cutaneous antigens, especially those of the dermal-epidermal junction, we conducted a retrospective analysis of all cutaneous direct immunofluorescence studies performed in patients with B-cell neoplasia who presented with cutaneous lesions requiring a skin biopsy. Patients with linear deposits of immunoglobulin or C3 molecules at the dermal-epidermal junction were studied further, using immunoblotting and immunoelectron microscopy. Patients with no overt hematologic malignancies but with cutaneous lesions requiring direct immunofluorescence were studied as a control population. During the study period, the diagnosis of autoimmune blistering diseases of the dermal-epidermal junction was established in 9/102 (8.9% +/- 2%) patients with a B-cell lymphoid disorder, compared with 288/8,189 (3.5% +/- 0.04%) patients without underlying hemopathy (p < 0.01). Among the 9 patients, 7 were studied in detail. Immunologic studies demonstrated epidermolysis bullosa acquisita in 6 patients and cicatricial pemphigoid in 1. Autoimmune blistering diseases, especially epidermolysis bullosa acquisita, are part of the spectrum of autoimmune disorders associated with B-cell neoplasia.

Immune-mediated destruction of melanocytes in halo nevi is associated with the local expansion of a limited number of T cell clones.

The beta-chain repertoire of the T cells that infiltrate spontaneously regressing nevi (the halo nevus phenomenon) was studied. In addition to the infiltration of the halo nevi by cutaneous lymphocyte-associated Ag-positive lymphocytes, oligoclonal expansion of T cells was observed in all halo nevi of all patients. T cells using the same TCR beta-chain were observed in distinct halo nevi of the same patient but not in his peripheral blood, demonstrating a local expansion of common clones that are most likely activated by the Ag(s) shared by independent halo nevi of the same patient.

[Adult T-cell lymphoma associated with HTLV-1: a familial form]. / Lymphome à cellules T de l'adulte associé à l'HTLV-1: une forme familiale.

BACKGROUND: Adult T-cell leukemia-lymphoma (ATL) can occur in siblings infected with HTLV-1. CASE REPORTS: Two Caribbean siblings developed ATL a few years apart. One case has been reported previously. Both individuals had peripheral lymph node T-cell lymphoma and a few atypical lymphocytes on blood smear. Lymphocytosis, bone marrow biopsy, abdominal computed tomographic scanning, and chest radiography were normal. Clonal rearrangement of T-cell receptor was present in skin lesions for both patients and in the blood for one. HTLV-1 serology was positive. Clonal integration of HTLV-1 provirus was demonstrated in skin lesions in one patient and in blood lymphocytes in the other. Chemotherapy, then interferon alpha, were unsuccessful in the first patient. Topical metchloretamine was partially effective for the second patient. DISCUSSION: ATL in siblings is explained by mother-to-child transmission of HTLV-1 infection during breastfeeding.