E. Mahé

Cutaneous Adverse Events in Renal Transplant Recipients Receiving Sirolimus-based Therapy1

Background. Sirolimus is an immunosuppressive drug recently developed for organ transplantation. Its mechanism of action, independent of calcineurin, is different from that of cyclosporine and tacrolimus, two calcineurin inhibitors (CIs). Because the toxicity of CIs is partly the result of calcineurin blockade, sirolimus exhibits a different toxicity profile. In this study, we evaluated the profile, frequency, and severity of cutaneous adverse events in renal transplant recipients receiving sirolimus-based therapy. Patients and Methods. A systematic and in-depth evaluation of skin, mucous membranes, nails, and hair was performed in 80 renal transplant recipients receiving sirolimus-based therapy. The mean duration of the graft was 6 years and of sirolimus treatment was 18 months. Mycophenolate mofetil and steroids were combined with sirolimus for 74 patients. Sirolimus was used as first immunosuppressive therapy for 36 patients, and 44 patients were switched from CIs to sirolimus. Results. Seventy-nine patients (99%) experienced cutaneous adverse events. Twenty patients (25%) demonstrated serious adverse events, and six patients (7%) stopped sirolimus during the 3 months after the study because of cutaneous events. The most frequent of these were pilosebaceous apparatus involvement, including acne-like eruptions (46%), scalp folliculitis (26%), and hidradenitis suppurativa (12%); edematous complaints, including chronic edemas (55%) and angioedema (15%); mucous membrane disorders, including aphthous ulceration (60%), epistaxis (60%), chronic gingivitis (20%), and chronic fissure of the lips (11%); and last, nail disorders including chronic onychopathy (74%) and periungual infections (16%). Conclusions. Skin disorders are frequent in renal transplant recipients receiving sirolimus as a long-term therapy. Despite the usually mild nature of skin events, they are often the reason for stopping sirolimus.

Drug‐induced hypersensitivity syndrome associated with Epstein–Barr virus infection

Summary Association of drug‐induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV‐6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant‐induced hypersensitivity syndrome. We report a case of severe allopurinol‐induced hypersensitivity syndrome with pancreatitis associated with Epstein–Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti‐EBV early antigen (EA) IgM antibodies and an increase in anti‐EBV EA IgG antibodies, whereas no anti‐EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV‐6 was suggested only by the presence of anti‐HHV‐6 IgM antibodies, but HHV‐6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV‐6 or CMV, in the development of drug‐induced hypersensitivity syndrome.

CD30+ T-cell lymphoma in a patient with psoriasis treated with ciclosporin and infliximab

Summary There is a known relationship between the use of immunosuppressive therapies and the development of lymphoproliferative malignancies. These lymphomas are mainly B‐cell nonHodgkins lymphomas associated with Epstein–Barr virus. Most cases concern classical immunosuppressive treatments including ciclosporin and methotrexate. A relationship between the new antitumour necrosis factor (TNF)‐α agents and lymphoproliferative malignancies is debated. Patients with psoriasis on immunosuppressive therapies, mainly ciclosporin, are considered to have a low risk of developing lymphoid proliferation. We report a patient with erythrodermic psoriasis treated with ciclosporin and infliximab who developed a CD30+ T‐cell lymphoma. This lymphoma regressed after stopping these treatments. In this case, the anti‐TNF‐α agent may have played a role in association with ciclosporin in the development of the lymphoproliferative disorder. Whereas the combination of anti‐TNF‐α therapies with methotrexate has been well studied, their combination with ciclosporin has been evaluated only in a few patients. Psoriatic patients who may require anti‐TNF‐α treatment have often been or will be treated with ciclosporin. The combination of ciclosporin and anti‐TNF‐α warrants further investigation.

Subcutaneous fat necrosis of the newborn: a systematic evaluation of risk factors, clinical manifestations, complications and outcome of 16 children

Background  Subcutaneous fat necrosis (SFN) of the newborn is a rare acute transient hypodermatitis that develops within the first weeks of life in term infants. It often follows a difficult delivery. Prognosis is generally good except for the development of hypercalcaemia in severe cases. Only several case reports or small patients series have been published.

Segmental and nonsegmental childhood vitiligo has distinct clinical characteristics: A prospective observational study

BACKGROUND Vitiligo often starts in childhood. It is traditionally divided into segmental vitiligo and nonsegmental vitiligo. There are limited data regarding the clinical characteristics of both forms and no comparative study has been performed. OBJECTIVE To compare the clinical features of nonsegmental and segmental vitiligo in children. PATIENTS AND METHODS We performed a prospective observational study. Consecutive children with vitiligo seen between October 2005 and December 2007 in the 11 French Departments of Pediatric Dermatology were included. A standardized evaluation was completed after total body clinical examination. A second examination was performed 1 year after inclusion. The clinical characteristics of segmental vitiligo and nonsegmental vitiligo were compared. RESULTS A total of 114 children with vitiligo were included. Compared with segmental vitiligo, nonsegmental vitiligo was associated with a higher number of lesions (more than 5 patches in 65.17% vs 20% of patients, P < .0001) and a larger body surface area of involvement (9.8% +/- 2.51% vs 3.48% +/- 1.6%, P +/- .01). A higher incidence of the Koebner phenomenon (47.19% vs 24%, P = .03), and more frequent progression of the disease (23.29% vs 5.56%, P = .043) were found in nonsegmental vitiligo. Hyperpigmented rims surrounding patches of vitiligo were only seen in nonsegmental vitiligo (8.99% vs 0% (P = .007). Sixty-four children (56%) had laboratory investigations performed; thyroid abnormalities were found only in nonsegmental vitiligo (11.23% vs 0%, P = .0001). LIMITATIONS Not all patients underwent laboratory investigations. CONCLUSIONS Segmental and nonsegmental types of vitiligo have distinguishing clinical characteristics.

Neonatal blue-light phototherapy does not increase nevus count in 9-year-old children.

OBJECTIVE. One of the most important risk factors for melanoma is the number of acquired common and atypical nevi in childhood. The role played by neonatal blue-light phototherapy in the increasing incidence of common and atypical melanocytic nevi in childhood or adolescence has been discussed recently with discordant results. PATIENTS AND METHODS. We designed a multicenter study to assess the effects of neonatal blue-light phototherapy on nevus count in a cohort of 9-year-old children. We counted back and arm nevi as a function of size in 828 children included in a French photoprotection educational campaign. History of neonatal phototherapy, phototype, skin, hair and eye color, and sunburn were assessed through questionnaires to which both parents and children responded, and a nevus count was performed by trained nurses blinded to phototherapy history. RESULTS. Mean nevus count was 16.7 per child. Twenty-two percent of the children had received neonatal blue-light phototherapy. Neonatal phototherapy had no effect on the nevus count irrespective of nevi location, nevi size, or phototype of the children. A light phototype, skin, and hair color; blue/green eyes; and history of sunburn were closely correlated with an increase in nevus count. CONCLUSIONS. This study found no evidence for a major role of blue-light phototherapy on nevus count in 9-year-old children. It underlines the dominant effect of phototype characteristics and history of sunburn in childhood on the early development of melanocytic nevi.

Childhood‐onset psoriasis: association with future cardiovascular and metabolic comorbidities

Psoriasis is associated with higher prevalences of cardiovascular and metabolic comorbidities in adults but the relationship of age at onset and those prevalences is unknown.

Propranolol-resistant infantile haemangiomas

Propranolol is now widely used to treat severe infantile haemangiomas (IHs). Very few cases of propranolol‐resistant IH (PRIH) are mentioned in the literature.

Outdoor sports and risk of ultraviolet radiation-related skin lesions in children: evaluation of risks and prevention

Background  Excessive ultraviolet (UV) radiation exposure can cause skin cancers, skin photoageing and cataracts. Children are targeted by sun‐protection campaigns because high sun exposure and sunburn in childhood increase the risk of melanoma in adulthood. Little information is available about UV radiation risk and exposure in children who take part in outdoor sports.

Angioedema in Renal Transplant Recipients on Sirolimus

Background:Most drug-associated angioedemas are induced by angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, or nonsteroidal anti-inflammatory drugs. Recently, the responsibility of immunosuppressive agents given to transplant recipients in the development of angioedema has been discussed. Objective: To describe, in detail, angioedema episodes in renal transplant recipients (RTRs) on sirolimus. Methods: A cross-sectional study in a university hospital. Eighty consecutive RTRs on sirolimus were studied. Results: Angioedema without urticaria occurred a mean of 5 times in 12/80 (15%) RTRs taking sirolimus. It was predominantly located on the face (83%), with mucous membrane involvement in 7 (58%) patients, and was life threatening in 1. Another putative cofactor for angioedema without urticaria was identified in 9 (75%) patients: drugs (n = 8), food allergy or physical activity (n = 3). Tacrolimus intake was significantly associated with sirolimus-associated angioedema. Conclusion: Our results suggested a causal relationship between sirolimus and angioedema in RTRs.