Jean-Marie Naeyaert

The Quest for the Mechanism of Melanin Transfer

Skin pigmentation is accomplished by production of melanin in specialized membrane‐bound organelles termed melanosomes and by transfer of these organelles from melanocytes to surrounding keratinocytes. The mechanism by which these cells transfer melanin is yet unknown. A central role has been established for the protease‐activated receptor‐2 of the keratinocyte which effectuates melanin transfer via phagocytosis. What exactly is being phagocytosed – naked melanin, melanosomes or melanocytic cell parts – remains to be defined. Analogy of melanocytes to neuronal cells and cells of the haemopoietic lineage suggests exocytosis of melanosomes and subsequent phagocytosis of naked melanin. Otherwise, microscopy studies demonstrate cytophagocytosis of melanocytic dendrites. Other plausible mechanisms are transfer via melanosome‐containing vesicles shed by the melanocyte or transfer via fusion of keratinocyte and melanocyte plasma membranes with formation of tunnelling nanotubes. Molecules involved in transfer are being identified. Transfer is influenced by the interactions of lectins and glycoproteins and, probably, by the action of E‐cadherin, SNAREs, Rab and Rho GTPases. Further clues as to what mechanism and molecular machinery will arise with the identification of the function of specific genes which are mutated in diseases that affect transfer.

Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study

Objectives: The safety and potential efficacy of rituximab was examined in diffuse cutaneous systemic sclerosis (dc-SSc). Methods: A 24 week open-label study in which eight patients with dc-SSc received an infusion of 1000 mg rituximab administered at baseline and day 15, together with 100 mg methylprednisolone at each infusion. Assessment included CD19+ peripheral blood lymphocyte number, skin sclerosis score, indices of internal organ functioning, the health assessment questionnaire disability index, the 36-item Short Form health survey and histopathological evaluation of the skin. Results: Ritixumab induced effective B-cell depletion in all patients (<5 CD19+ cells/μl blood). There was a significant change in skin score at week 24 (p<0.001). Also, significant improvements were measured in the dermal hyalinised collagen content (pu200a=u200a0.014) and dermal myofibroblast numbers (pu200a=u200a0.011). Two serious adverse events occurred, which were thought to be unrelated to the rituximab treatment. Conclusions: Rituximab appears to be well tolerated and may have potential efficacy for skin disease in dc-SSc. This study is registered with ClinicalTrials.gov, number NCT00379431.

Acanthosis nigricans in a child with mild osteochondrodysplasia and K650Q mutation in the FGFR3 gene

A girl with a mild sporadic osteochondrodysplasia (OCD) similar to hypochondroplasia but with significant short stature is reported. She has been followed clinically between the ages of 9 months and 14 years. Growth remained normal throughout childhood with stature evolving about 3.5 SDs under the mean for age. By 8 years of age gradually appearing acanthosis nigricans (AN) in the neck and flanks was histopathologically confirmed. It provided the new incentive to search for specific FGFR3 mutations associated with this dermatologic abnormality. This resulted in the identification of the 1948Au2009>u2009C transversion predicting the K650Q missense substitution in the FGFR3 protein. Besides the expansion of the phenotypic spectrum of FGFR3‐related OCDs to HCH with AN, this observation underscores the continuing adverse effect of this specific mutation upon the normal inhibitory signaling of the receptor at least in epidermal cells.

Incidence of scabies in Belgium

A prospective survey on scabies in Ghent, Belgium was performed in 2004. Sixty-four individual cases were reported, corresponding to a crude incidence rate of 28/100,000 inhabitants. The incidence was higher in the elderly (51/100,000 in persons aged >75 years) and a higher incidence was also found in immigrants (88/100,000). More than 40% of the registered scabies patients had symptoms for more than 4 weeks at the time of presentation. In 54% of the consultations, the patient had already consulted a physician for his/her skin problem. Of this group, 44% had not yet received any scabicidal treatment, indicating that scabies was not yet diagnosed or that an inappropriate treatment was prescribed. The observations suggest that the diagnosis and/or treatment of scabies in this region can still be improved.

Cellular grafting and repigmentation in vitiligo

Many therapeutic options are available to repigment vitiligo but none are uniformly successful. For vitiligo that is refractory to medical therapy, cellular grafting is an innovative procedure that offers the potential to repigment large areas of achromic lesion from a small piece of donor skin. The techniques include transplantation of autologous cultured melanocytes, cocultured melanocytes and keratinocytes, and noncultured epidermal cells suspension. Advances in recipient-site preparation and culturing techniques have greatly improved the efficiency of this procedure, achieving good to excellent repigmentation rates for stable vitiligo.

POLYARTERITIS NODOSA MIMICKING POLYMYALGIA RHEUMATICA

Abstract: We report a case of polyarteritis nodosa with a clinical presentation mimicking polymyalgia rheumatica, as well as pathological findings of non-giant-cell arteritis on temporal artery biopsy with symptoms of jaw claudication. Although certain clinical syndromes have been attributed to specific types of systemic vasculitis, considerable overlap occurs. Obtaining tissue biopsy in cases of vasculitis is mandatory for diagnosis and classification.