Unique B cell differentiation profile in tolerant kidney transplant patients.

Operationally tolerant patients (TOL) display a higher number of blood B cells and transcriptional B cell signature. As they rarely develop an allo-immune response, they could display an abnormal B cell differentiation. We used an in vitro culture system to explore T-dependent differentiation of B cells into plasma cells. B cell phenotype, apoptosis, proliferation, cytokine, immunoglobulin production and markers of differentiation were followed in blood of these patients. Tolerant recipients show a higher frequency of CD20(+) CD24(hi) CD38(hi) transitional and CD20(+) CD38(lo) CD24(lo) naïve B cells compared to patients with stable graft function, correlating with a decreased frequency of CD20(-) CD38(+) CD138(+) differentiated plasma cells, suggestive of abnormal B cell differentiation. B cells from TOL proliferate normally but produce more IL-10. In addition, B cells from tolerant recipients exhibit a defective expression of factors of the end step of differentiation into plasma cells and show a higher propensity for cell death apoptosis compared to patients with stable graft function. This in vitro profile is consistent with down-regulation of B cell differentiation genes and anti-apoptotic B cell genes in these patients in vivo. These data suggest that a balance between B cells producing IL-10 and a deficiency in plasma cells may encourage an environment favorable to the tolerance maintenance.

Topical corticosteroid phobia in atopic dermatitis: a study of its nature, origins and frequency.

BACKGROUND: Topical corticosteroids remain the mainstay of atopic dermatitis therapy. Many atopic dermatitis therapeutic failures appear to be attributable to poor adherence to treatment due to topical corticosteroid phobia. OBJECTIVES: To assess the facets, origins and frequency of fear of topical corticosteroid use among patients with atopic dermatitis. METHODS: A questionnaire comprising 69 items, generated from information gathered during interviews with 21 patients and 15 health professionals, was given to consecutive patients consulting at the outpatient dermatology departments of five regional university hospitals or with 53 dermatologists in private practice. RESULTS: A total of 208 questionnaires were analysed (including 144 from parents and 87 from adult patients, 27 of whom were also parents); 80·7% of the respondents reported having fears about topical corticosteroids and 36% admitted nonadherence to treatment. A correlation was found between topical corticosteroid phobia and the need for reassurance, the belief that topical corticosteroids pass through the skin into the bloodstream, a prior adverse event, inconsistent information about the quantity of cream to apply, a desire to self-treat for the shortest time possible or poor treatment adherence. Topical corticosteroid phobia was not correlated with atopic dermatitis severity. CONCLUSION: Topical corticosteroid phobia is a genuine and complex phenomenon, common among French patients with atopic dermatitis, that has an important impact on treatment compliance.

[Sweet's syndrome as the presenting manifestation of relapsing polychondritis]. / Syndrome de Sweet révélant une polychondrite atrophiante.

Relapsing polychondritis (RP) is a rare disorder characterized by recurrent inflammatory episodes involving various cartilages. The clinical course of RP is variable, and dermatologic manifestations are uncommon. We report a 73-year-old patient who presented with a neutrophilic dermatosis (Sweet's syndrome) as the initial manifestation of RP. There was no evidence for a myelodysplastic syndrome, as it has been previously reported with RP, but the patient was followed-up for an indolent and untreated chronic lymphocytic leukaemia. Complete remission was obtained with oral corticosteroids. This report highlights the clinical spectrum of the RP.

[Systemic sarcoidosis after treatment with pegylated interferon-alpha]. / Sarcoïdose systémique au décours d'un traitement par interféron-alpha pégylé

A few cases of sarcoidosis have been reported in the course of chronic hepatitis C, with or without alpha-interferon treatment. We report a 54-year-old woman who presented a typical sarcoidosis in this context. The sarcoidosis involved skin, lungs and eyes. There are data in the literature supporting a pathogenic link between alpha-interferon and sarcoidosis: alpha-interferon possessing a non-specific immunologic inductor. The treatment of the sarcoidosis in this context is difficult and has to be adjusted to both the severity of the sarcoidosis and the viral hepatitis. Although sarcoidosis induced by alpha-interferon is rare, clinicians must be aware of this association.

[Sarcoidosis-like granulomatosis revealing a tertiary syphilis]. / Granulomatose pseudosarcoïdosique révélant une syphilis tertiaire.

Numerous disorders can cause a systemic granulomatosis. We report a patient who presented a biopsy proven granulomatous skin eruption, fever, and atypical thoracic pain. Electrocardiogram showed a first-degree atrioventricular heart bloc. During follow-up he developed a panuveitis and oral corticosteroids were started. A diagnosis of systemic sarcoidosis was considered. Because of unfavourable ophthalmologic outcome, investigations were enlarged and revealed a highly positive serology for syphilis and VDRL both in serum and cerebrospinal fluid. Clinical outcome with penicillin G therapy was favorable. This observation reminds us the clinical polymorphism of syphilis, which can be presented as a systemic granulomatosis.

[Congenital histiocytoma: a benign disease]. / Histiocytome congénital: une lésion bénigne.

BACKGROUND: We report on a newborn presenting a solitary congenital skin nodule due to Langerhans cell histiocytosis. This benign lesion is rare and has been described in the literature under a variety of names; there is no consensus regarding treatment. CASE REPORT: A 28-day-old newborn presented with a solitary congenital blue-brown nodule measuring 1cm on the left iliac fossa. Histological examination of a skin biopsy showed a proliferation of histiocytes throughout the dermis with an immunohistochemical profile of Langerhans cells. The lesion resolved spontaneously, with rapid reduction of the infiltration, and at 16 weeks only a pigmented scar remained. DISCUSSION: Thirty-eight similar cases have been reported in the literature under a variety of different names. The lesions noted consisted of a solitary brownish nodule measuring 1cm which was congenital in almost all cases, often ulcerated and exhibited no predilection for any particular body site. Histological examination revealed dermal proliferation of Langerhans cells. Electronic microscopy revealed dense intracytoplasmic bodies and Birbeck's granules. Laboratory and radiological tests did not show systemic involvement in any cases. All lesions other than those surgically removed regressed spontaneously within a mean 8 weeks. It appears necessary to differentiate between congenital and other forms of histiocytoma since therapeutic strategies differ. Spontaneous resolution of lesions and lack of systemic involvement militate in favour of simple clinical follow-up, with surgical excision and further tests required only for cases lasting 6 months and beyond.

[Bursitis due to Mycobacterium intracellulare in an immunocompetent patient]. / Bursite fistulisée à Mycobacterium intracellulare chez un adulte immunocompétent.

BACKGROUND: Cutaneous infections due to Mycobacterium intracellulare are infrequent. We report a case of bursitis in an immunocompetent patient. CASE-REPORT: A 80-year-old patient with a history of tuberculosis reported swelling of the elbow for six months with effusion due to olecranon bursitis, progressing to an abscess and skin ulceration. Examination of the synovial fluid revealed the presence of M. intracellulare. Histologic investigations showed epithelioid and gigantocellular granulations. Screening for immunodepression was negative. Treatment with clarithromycin and rifabutin proved effective, with partial healing at three months, although hepatic and ocular side effects occurred. DISCUSSION: While osteomyelitis, arthritis and cutaneous infections due to M. intracellulare have been described in immunocompromised patients, there are very few reported cases concerning immunocompetent individuals, and these suggest the possibility of special individual sensitivity to mycobacterial infections. Genetic mutations of the interleukin-12-interferon-gamma pathway involved in the immune response to mycobacterial infections have been demonstrated. Autoantibodies against interferon-gamma have also been described. Mycobacterium avium-intracellulare is resistant to the classical antibiotics used in tuberculosis. As in pulmonary infections, antibiotics with proven in vivo and in vitro efficacy must be used, taking into account the antibiogram and potential side effects, particularly for combined clarithromycin and rifabutin. CONCLUSION: This case report emphasizes the benefits of routine mycobacterial investigation of synovial fluid samples.