Plasma cell-directed therapies in monoclonal gammopathy-associated scleromyxedema.

Scleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and leonine facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell-directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor ß and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.

Neurofibromatosis 1 French national guidelines based on an extensive literature review since 1966.

Neurofibromatosis type 1 is a relatively common genetic disease, with a prevalence ranging between 1/3000 and 1/6000 people worldwide. The disease affects multiple systems with cutaneous, neurologic, and orthopedic as major manifestations which lead to significant morbidity or mortality. Indeed, NF1 patients are at an increased risk of malignancy and have a life expectancy about 10-15 years shorter than the general population. The mainstay of management of NF1 is a patient-centered longitudinal care with age-specific monitoring of clinical manifestations, aiming at the early recognition and symptomatic treatment of complications as they occur. Protocole national de diagnostic et de soins (PNDS) are mandatory French clinical practice guidelines for rare diseases required by the French national plan for rare diseases. Their purpose is to provide health care professionals with guidance regarding the optimal diagnostic and therapeutic management of patients affected with a rare disease; and thus, harmonizing their management nationwide. PNDS are usually developed through a critical literature review and a multidisciplinary expert consensus. The purpose of this article is to present the French guidelines on NF1, making them even more available to the international medical community. We further dwelled on the emerging new evidence that might have therapeutic potential or a strong impact on NF1 management in the coming feature. Given the complexity of the disease, the management of children and adults with NF1 entails the full complement healthcare providers and communication among the various specialties.

Fatal toxic epidermal necrolysis in a patient on teriflunomide treatment for relapsing multiple sclerosis.

We report a case of toxic epidermal necrolysis in a 46-year-old woman on teriflunomide treatment. Such a severe adverse cutaneous drug reaction with this new therapy for relapsing forms of multiple sclerosis should be early recognized in order to ensure the rapid withdrawal of the drug.

Prognostic value of skin manifestations of infective endocarditis.

IMPORTANCE: Infective endocarditis (IE) is a rare disease with poor prognosis. When IE is suspected, skin examination is mandatory to look for a portal of entry and classic skin lesions to help diagnose and manage the condition. OBJECTIVES: To describe the prevalence of and factors associated with dermatological manifestations in patients with definite IE. DESIGN: Observational, prospective, population-based epidemiological study between January 1 and December 31, 2008. Subsequently, collected dermatological data were subjected to post hoc analysis. SETTING AND PARTICIPANTS: Patients (n = 497) diagnosed in 7 French regions and hospitalized in France for definite IE satisfying modified Duke criteria. MAIN OUTCOMES AND MEASURES: Patient and disease epidemiological information was collected, focusing on the most classic dermatological manifestations of IE (Osler nodes, Janeway lesions, purpura, and conjunctival hemorrhages). Disease outcome was also recorded. RESULTS: Among 497 definite IE cases, 487 had known dermatological status. Of 487 cases, 58 (11.9%) had skin manifestations, including 39 (8.0%) with purpura, 13 (2.7%) with Osler nodes, 8 (1.6%) with Janeway lesions, and 3 (0.6%) with conjunctival hemorrhages (5 patients had 2 skin manifestations). Patients with skin manifestations had a higher rate of IE-related extracardiac complications than patients without skin manifestations, particularly cerebral emboli (32.8% vs 18.4%, P = .01), without increased mortality. Patients with purpura had larger cardiac vegetations (18.1 vs 13.7 mm, P = .01), and Janeway lesions were associated with more extracerebral emboli (75.0% vs 31.8%, P = .02). CONCLUSIONS AND RELEVANCE: Specific skin manifestations of IE are associated with a higher risk of complications and should alert physicians to examine for extracardiac complications, notably with cerebral imaging.

Eosinophilic fasciitis: a rare skin sclerosis.

Eosinophilic fasciitis (Schulman's syndrome) is a rare disease with specific clinical symptoms such as the groove sign which facilitate diagnosis. We report a typical case of eosinophilic fasciitis in an otherwise healthy 49-year-old man who presented with "prayer and groove signs". Histological analysis showed sclerosis and eosinophilic infiltration of the fascia. The patient was successfully treated with systemic corticotherapy and Cyclosporine. A short review of the clinicopathological features of the lesions is presented.