Uveitis in patients with late-stage cutaneous melanoma treated with vemurafenib.

IMPORTANCE: This case series highlights the risk of uveitis in patients treated with vemurafenib for unresectable or metastatic cutaneous melanoma. OBJECTIVE: To assess the occurrence and severity of uveitis as an adverse effect of vemurafenib therapy. DESIGN, SETTING, AND PATIENTS: In this observational small case series, data were collected successively from May 1, 2012, through February 31, 2013, from patients with clinical signs of ocular inflammation treated with vemurafenib at the Department of Ophthalmology, Cochin-Hôtel-Dieu Hospital. MAIN OUTCOMES AND MEASURES: Patients' demographics, vemurafenib dosages, and the intervals between the onset of treatment and the first ocular symptoms were recorded. The characteristics of ocular inflammatory manifestations were analyzed. The effect of the discontinuation of vemurafenib therapy on ocular manifestations was assessed, as well as the effect of rechallenging when vemurafenib was reintroduced. RESULTS: Seven patients (mean [SD] age, 74.7 [4.0] years) had uveitis. The vemurafenib dose was 960 mg twice per day in 6 patients and a half dose in 1 patient. The mean (SD) time until the appearance of ocular signs was 5.6 (2.3) months (range, 19 days to 7 months), and inflammation ranged from mild or low-grade anterior uveitis to severe explosive panuveitis complicated by retinal detachment. Signs of ocular inflammation were always bilateral. Optical coherence tomography revealed a macular edema in only 1 of the 7 patients. Clinical improvement occurred when vemurafenib therapy was stopped in 5 of 7 patients. The rechallenge at treatment reintroduction was positive in 2 of 7 patients. CONCLUSIONS AND RELEVANCE: This small case series highlights that uveitis can be a noteworthy adverse effect of vemurafenib therapy in patients with metastatic cutaneous melanoma. However, these cases of uveitis were usually restricted to the anterior segment and manageable with local corticosteroid therapy, which justified the continuation of vemurafenib therapy because the benefits regarding the patients' survival were greater than the risk to their vision.

Severe cutaneous bacillus Calmette-Guérin infection in immunocompromised children: the relevance of skin biopsy.

Disseminated bacillus Calmette-Guérin infection (BCGitis) is an uncommon condition which is usually associated with primary immunodeficiency. Skin histopathology findings have been described in rare cases only. A retrospective clinicopathological study was performed to assess the potential utility of skin biopsies in the diagnosis, prognosis and follow-up of these patients. Four cases of disseminated BCGitis in children with Severe Combined ImmunoDeficiency were biopsied before and after Haematopoietic Stem Cell Transplantation (HSCT). The results were compared to the clinical and immunological status of the children. Early skin biopsies revealed either dense dermal infiltration by foamy macrophages filled with acid fast bacilli (AFB) or mycobacterial spindle-cell pseudotumors rich in AFB. There were no granulomas. These patterns led to the diagnosis of disseminated BCGitis potentially caused by severe immunodeficiency. After HSCT, repeated skin biopsies were performed on persistent or new cutaneous lesions to rule out immune reconstitution inflammatory syndrome and to check for tuberculoid granulomas. One patient died of BCGitis combined with graft versus host disease. The 3 others presented with progressive-onset well differentiated granulomas over a long period and recovered. Skin biopsy is a useful part of the diagnostic workup for disseminated BCGitis, directing the clinician toward severe immunodeficiency. Moreover, skin biopsy may be a useful means of monitoring immune restoration for prognostic purposes.

A pretibial plaque in a five and a half year-old girl.

A five and a half year-old girl presented with a reddish-brown plaque on her right anterior tibia, first observed 1 year previously and without any history of injury or insect bite. Histological examination showed a dense dermal infiltrate composed of plasma cells and small lymphocytes, combined with lymphocytic exocytosis in the epidermis and interface dermatitis. In addition, a second biopsy found small epithelioid granulomas within the lymphoplasmocytic infiltrate. Infection was ruled out. No clonality was found. None of the treatments attempted was successful (antibiotics and steroids), and the lesion was stable but did not improve for 4 years. The same features typical of lymphoplasmocytic pseudolymphoma were observed on a third biopsy. A diagnosis of "pretibial lymphoplasmocytic plaque" was made on the basis of clinical and histological findings. Recently, 3 other cases of this type of lymphocytic and plasma cell cutaneous infiltrate with very distinctive clinical and histopathological features have been reported in children. Our case is instructive because it presents new and as yet undocumented histopathologic features including a lichenoid reaction with vacuolization of the basal cell layer and numerous apoptotic bodies, apparent in 2 of the 3 biopsies, and hypervascularity with thick-walled blood vessels lined with plump endothelial cells in the upper dermis. The clinicopathological presentation of these cases, including ours, is homogenous suggesting a specific entity described as "pretibial lymphoplasmocytic plaque in children". This seems to be a benign, chronic, reactive process, probably arising secondary to a local response to an unknown antigen.