Subchondral involvement in osteonecrosis of the femoral head: insight on local composition, microstructure and vascularization.

OBJECTIVE: To determine changes of subchondral bone composition, micro-structure, bone marrow adiposity and micro-vascular perfusion in end-stage osteonecrosis of the femoral head (ONFH) compared to osteoarthritis (OA) using a combined in vivo and ex vivo approach. DESIGN: Male patients up to 70 years old referred for total hip replacement surgery for end-stage ONFH were included (n = 14). Fifteen patients with OA were controls. Pre-operative MRI was used to assess bone perfusion (dynamic contrast-enhanced (DCE) sequences) and marrow fat content (chemical shift imaging). Three distinct zones of femoral head subchondral bone - necrotic, sclerotic, distant - were compared between groups. After surgery, plugs were sampled in these zones and Raman spectroscopy was applied to characterize bone mineral and organic components (old and newly-formed), and contrast-enhanced micro-computed tomography (CE-µCT) to determine bone micro-structural parameters and volume of bone marrow adipocytes, using conventional 2D histology as a reference. RESULTS: In the necrotic zone of ONFH patients compared to OA patients: 1) the subchondral plate did not exhibit significant changes in composition nor structure; 2) the volume fraction of subchondral trabecular bone was significantly lower; 3) type-B carbonate substitution was less pronounced, 4) collagen maturity was more pronounced; and 5) bone marrow adipocytes were significantly depleted. The sclerotic zone from the ONFH group showed greater trabecular thickness, and higher DCE-MRI AUC and Ktrans. Volume fraction of subchondral bone, trabecular number, and Kep were significantly lower in the distant zone of the ONFH group. CONCLUSIONS: This study demonstrated alterations of subchondral bone microstructure, composition, perfusion and/or adipose content in all zones of the femoral head.

[Atypical Sézary syndrome in a young subject]. / Syndrome de Sézary atypique chez un sujet jeune.

INTRODUCTION: Sézary syndrome accounts for 5% of cutaneous T-cell lymphomas, with mean age of onset of 60 years. Erythroderma associated with palmoplantar keratoderma and lymphadenopathy is the usual clinical presentation, but the disease has potentially confusing polymorphic clinical features. PATIENTS AND METHODS: We report the case of a 27-year-old patient with no notable disease history, presenting generalized non-pruritic dermatosis for 3 months, with erythema and papules, and follicular distribution, localized to the limbs, the trunk and the face. Palmoplantar keratoderma was associated with acral edema. The clinical presentation was initially evocative of pityriasis rubra pilaris. Laboratory tests showed hyperlymphocytosis with Sézary cells in the blood. A diagnosis of grade IVA Sézary syndrome was made based on the skin biopsy results and the PET scan. Screening for KIR3DL2 on T-cells in blood was positive. Extracorporeal photochemotherapy was initiated but cutaneous relapse occurred, leading to combined treatment with bexarotene, which proved ineffictive. Despite numerous chemotherapies (cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone, then dexamethasone, oxaliplatin and cytarabine, associated with brentuximab, vedotin, and, ultimately, clofarabine and endoxan), the patient died after 9 months. DISCUSSION: Our case illustrates an atypical clinical presentation of cutaneous lymphoma in a young patient. With a fatal outcome in 9 months despite 5 different lines of treatment, our case highlights the aggressive nature of Sézary syndrome as well as the difficulties involved in treating this disease. CONCLUSION: A diagnosis of Sézary syndrome must be considered in the event of atypical dermatosis in patients of all ages. The presence of lymphomatous clonal cells and Sézary cells in the blood, immunophenotyping of lymphocytes in blood and marrow, and a second reading of the cutaneous biopsy results enabled us to make a diagnosis of Sezary syndrome.

[Angiosarcoma in primary lymphoedema: A rare complication]. / Angiosarcome sur lymphœdème primaire du membre inférieur : une complication rare.

BACKGROUND: Chronic lymphoedema is classically complicated by recurring episodes of cellulitis. Degeneration to the angiosarcoma form (Stewart-Treves syndrome) is much less common. It occurs mainly in the upper limbs following surgery or radiotherapy for mammary neoplasia. Herein we report a rare case of Stewart-Treves syndrome (STS) of the lower limb as a complication of congenital lymphoedema. PATIENTS AND METHODS: A 69-year-old woman treated for bilateral lower-limb oedema present for 30years developed painful necrotic lesions in her left lower limb. A diagnosis of angiosarcoma was made based on biopsy of a nodular lesion. Since surgical excision was precluded by the extent of the lesions, chemotherapy was initiated with paclitaxel 175mg/m2 every 21days. The outcome was rapidly unfavourable and the patient died at her home during the third course of treatment. DISCUSSION: Angiosarcoma is an extremely rare complication of primary lymphoedema; treatment is poorly codified and the prognosis is unfavourable.

[Vemurafenib-induced toxic epidermal necrolysis]. / Nécrolyse épidermique toxique au vemurafenib.

BACKGROUND: Herein we report the first case of toxic epidermal necrolysis (TEN) occurring with use of vemurafenib. PATIENTS AND METHODS: A 75-year-old female patient was being treated with vemurafenib for stage IV melanoma with BRAF V600E mutation. She suddenly presented fever, diffuse pruriginous maculopapular erythema, palpebral edema, palmar bulla, conjunctivitis, cheilitis and mucosal ulceration. The condition progressed towards detachment affecting 50% of the skin area. Cutaneous biopsy revealed lichenoid dermatosis, chiefly vesicular with numerous eosinophils. Direct immunofluorescence (IFD) was negative. Vemurafenib was the only drug to which the reaction was ascribable and we concluded on vemurafenib-induced TEN. DISCUSSION: To our knowledge, this is the first reported case of vemurafenib-induced TEN, but this adverse effect, although already described in the BRIM-3 study, appears rare in clinical practice. Other severe skin reactions have been described in the literature. These include a case of Stevens-Johnson syndrome in a female patient treated with vemurafenib and previously receiving ipilimumab. A more common occurrence is cutaneous reactions involving efflorescence of benign hyperkeratotic lesions, occasionally accompanied by authentic epidermal carcinoma or keratoacanthoma, and requiring regular dermatological monitoring of patients treated with vemurafenib. CONCLUSION: If maculopapular exanthema occurs under vemurafenib, continuation of this treatment should be reassessed since the risk of progression to a more serious condition such as TEN, as seen in the present case, cannot be ruled out.