Philippe Lauret

Evolution of chronic recurrent multifocal osteitis toward spondylarthropathy over the long term

OBJECTIVE To retrospectively assess, with a sufficiently long followup (mean 11.6 years; median 9 years), the long-term outcome of chronic recurrent multifocal osteitis (CRMO), a multifocal, inflammatory bone disease. METHODS Patients included were 8 children/adolescents and 7 adults with no family history of rheumatic disease who had been diagnosed as having CRMO between 1979 and 1995. Ten patients had undergone at least 1 bone biopsy of the lesions, with histologic examination and multiple cultures. In 1996, in addition to an in-depth interview, 12 patients underwent an extensive physical examination, laboratory evaluation, HLA-A, B, C, and DR typing, bone radiography and scintigraphy, and computed tomography scan of the sternoclavicular and sacroiliac joints. RESULTS Remission was observed in 3 patients. The other 12 patients developed various associations of vertebral (n = 10), sacroiliac (n = 6), anterior thoracic (n = 7), peripheral articular (n = 2), enthesopathic (n = 4), or dermatologic (palmoplantar pustulosis in 3 cases and psoriasis in 2) involvements. Spine involvement was the most common and occurred the earliest (median time to appearance after the onset of osteitis 5.63 years). Clinical sacroiliitis was always unilateral. No patients carried the HLA-B27 haplotype. CRMO responded well to nonsteroidal antiinflammatory drugs. Twelve patients met the European Spondylarthropathy Study Group criteria for spondylarthopathy. CONCLUSION After 10 years, CRMO had usually evolved to spondylarthropathy, but with certain features not usually seen in the latter: predominantly, unilateral sacroiliitis, no familial form, and no link with HLA-B27.

Manometry of the upper intestinal tract in patients with systemic sclerosis: A prospective study

OBJECTIVE To assess both the prevalence and the characteristics of motor disorders of the small bowel in patients with systemic sclerosis (SSc) and to investigate for an association between clinical manifestations in the upper intestinal tract, capillaroscopic features, esophageal motor impairment, and manometric evidence of motor disturbances. METHODS Fasting and postprandial motor activity of the upper intestinal tract was studied in 17 consecutive patients with SSc (6 with and 11 without clinical manifestations of small bowel involvement) and 17 age- and sex-matched healthy control subjects. RESULTS The prevalence of manometric evidence of intestinal involvement was as high as 88% in the SSc patients; normal motor activity was present in only 2 patients. The median values for duodenal and jejunal interdigestive phase III migrating motor complex duration, amplitude, and velocity and the postprandial motility index were therefore lower in SSc patients compared with controls. Our manometric findings indicated that there are both neuropathic and myopathic stages of upper intestinal tract dysfunction in SSc. Furthermore, no association could be found between the severity of the intestinal manometric abnormalities and clinical presentation, SSc subsets, disease score, capillaroscopic findings, or esophageal manometric impairment. CONCLUSION We suggest that manometry of the upper intestinal tract may be useful in SSc patients with clinical manifestations in the small bowel (i.e., malabsorption syndrome or pseudoobstruction) in that it can be used to accurately evaluate both the nature and the severity of motor disturbances. Furthermore, this procedure can be used to assist in the selection of patients who may require octreotide therapy.

Association of major aphthous ulcers and nicorandil.

Major aphthous ulcers are generally idiopathic but can occasionally be associated with HIV infection, Behcet’s disease, or neutropenia. We report on 16 cases of major aphthous mouth ulcers after use of nicorandil, a cardiovascular drug. The patients (nine men, seven women, median age 78 years [range 64–90]) were treated with nicorandil for angina pectoris (table). The median duration of treatment at the onset of aphthous ulcers was 12 months (range 2–36). 12 patients received 40 mg/day, and four 60 mg/day. In two patients, aphthous ulcers occurred when the dose was increased from 40 mg/day to 60 mg/day. Three patients had occasional minor aphthous stomatitis before treatment by nicorandil. The lesions, one to three in number, were typical painful major aphthous ulcers of more than 1 cm in diameter, and were located on the tongue, gingiva, or cheeks. There were no extraoral signs and laboratory investigations did not show abnormalities, white blood cell, haemoglobin, and platelet counts, erythrocyte sedimentation rates, and kidney and liver functions were normal. Histopathological assessment was done for five patients and showed non-specific ulceration. Viral, bacteriological, and fungal cultures done in three cases were negative. HIV tests done in the first three patients were negative. The median duration of each major aphthous stomatitis was 3 months (range 1–36). In the first six patients, toxic aphthous ulcers were not initially diagnosed and the patients were treated with thalidomide 25–50 mg/day (n=3) or colchicine 1 mg/day (n=3) and nicorandil was continued. Aphthous ulcers healed completely in 10–15 days in all these patients, but relapsed immediately when colchicine and thalidomide were stopped. Ulcers healed completely without scars in all 16 patients 1–3 weeks after nicorandil was discontinued. No patient relapsed during a median follow-up of 12 months (range 1–17). For ethical reasons we did not test rechallenge of nicorandil after the ulcers healed. Before this series, only two isolated cases of major aphthous ulcers induced by nicorandil were reported. Our results suggest a role for nicorandil in the onset of the major aphthous stomatitis since most of these patients had never previously had aphthous ulcers, and idiopathic major aphthous stomatitis generally begin in young patients; no other aetiology of major aphthous ulcers could be detected; the patients received many different drugs but nicorandil was the only drug common to them all; transient improvement was obtained with thalidomide or colchicine, RESEARCH LETTERS

Binding of autoantibodies is not restricted to desmosomes in pemphigus vulgaris

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune blistering diseases characterized by a loss of cell-cell adhesion and by autoantibodies directed against epidermal cadherins. PF antigen has been established as desmoglein I which is located strictly on the desmosome, whereas the precise ultrastructural localization of PV antigen remains unclear and controversial to date. To further investigate this question, we compared the location of immune deposits in 14 patients with PV and 10 patients with PF by both direct and indirect immunoelectron microscopy (IEM). Inclusion criteria were based upon clinical features, histological level of cleavage and characterization of circulating antibodies by Western blot on epithelial bovine tongue extracts. IEM was performed on unfixed 0.7-mm slices of skin for the direct technique or on normal skin for the indirect technique using peroxidase labelling. In PF, by both direct and indirect IEM, immune deposits were located on the extracellular part of desmosomes (desmoglea) in all the samples studied. In PV, by both direct and indirect IEM, deposits were situated on the desmoglea and along large portions of the keratinocyte membrane without desmosomal structures in 15 of the 18 samples studied and only on the desmoglea in 3 samples. These results suggest that, in contrast to PF, the target antigen in PV is not always restricted to desmosomes. As various types of adherens junctions have been reported to mediate cell adhesion in the epidermis, the PV antigen could be a component of desmosomes and of other focal adhesions.

Osteoarticular manifestations of pustulosis palmaris et plantaris and of psoriasis: two distinct entities.

OBJECTIVE: To test the hypothesis that pustulosis palmaris et plantaris and psoriatic arthritis (PsA) are two distinct diseases, and that the associated dermatoses are therefore also distinct diseases. METHODS: We prospectively performed clinical, radiological, biological, and bone scan investigations in 23 outpatients with pustolotic arthritis and 23 outpatients with PsA, matched by gender, age (+/- one year) and duration of arthritis (+/- two years). RESULTS: The anterior chest wall, especially the sternocostoclavicular joints, was more frequently involved in pustulotic arthritis than in PsA, both clinically (82% v 43%; p < 0.001) and radiologically (47% v 17%; p < 0.05). Sternocostoclavicular joints generally presented with erosive lesions in PsA, and with large ossifications in pustulotic arthritis. Peripheral joint involvement was mono- or oligoarticular, affecting proximal joints, in pustulotic arthritis (74% v 21%; p < 0.01), and polyarticular, involving small distal joints, in PsA (60% v 0%; p < 10(-4)), in which condition it was also more often erosive (43% v 8%; p < 0.01). The frequency of sacroiliitis and of spine involvement was similar in pustulotic arthritis and PsA. Biology and bone scan did not help distinguish between the two groups. CONCLUSIONS: Pustulotic arthritis and PsA are clinically and radiologically different, therefore pustulosis palmaris et plantaris and psoriasis are most probably distinct dermatological diseases.