Fibroblastic rheumatism: a report of 4 cases with potential therapeutic implications.

BACKGROUND: Fibroblastic rheumatism is a rare dermatoarthropathy characterized by the sudden onset of cutaneous nodules, flexion contractures, and polyarthritis. Histopathology in the correct clinical context confirms the diagnosis. Treatment is based on observational data from single case reports. OBJECTIVE: We describe 4 cases, review histologic findings, and discuss therapeutic responses. METHODS: Cases coded as fibroblastic rheumatism were retrieved from institutional and consultation files. Medical charts and biopsy specimens were reviewed. Elastic stains and immunostains for smooth muscle actin, S100, CD34, desmin, and epithelial membrane antigen were performed on selected cases. RESULTS: Four cases were identified. Patients displayed cutaneous nodules and arthralgias. Flexion contractures/decreased motion were present in two patients; one patient had associated Raynaud phenomenon and erosive joint disease. Biopsy specimens demonstrated a fibroblastic proliferation associated with a collagenous stroma. Growth patterns varied from cellular fascicles to paucicellular randomly arranged spindle cells. Elastic fibers were absent in all cases tested (3/3). Immunohistochemical stains demonstrated immunoreactivity for smooth muscle actin in one of 3 cases in a myofibroblastic pattern. Other stains were negative. One patient had complete resolution of disease with methotrexate. One patient partially responded to interferon-alfa and ribavirin and was subsequently treated with methotrexate with additional improvement. One patient had limited response to all therapies attempted. One patient was lost to follow-up. LIMITATIONS: Small sample size (n = 4) is a limitation. CONCLUSION: Our data expand the clinical, histologic, and therapeutic response data on fibroblastic rheumatism. Correlation with clinical history is critical to avoid misdiagnosis as other fibrosing lesions. Methotrexate and interferon-alfa are potential therapies.

A targeted Coch missense mutation: a knock-in mouse model for DFNA9 late-onset hearing loss and vestibular dysfunction.

Mutations in COCH (coagulation factor C homology) are etiologic for the late-onset, progressive, sensorineural hearing loss and vestibular dysfunction known as DFNA9. We introduced the G88E mutation by gene targeting into the mouse and have created a Coch(G88E/G88E) mouse model for the study of DFNA9 pathogenesis and cochlin function. Vestibular-evoked potential (VsEP) thresholds of Coch(G88E/G88E) mice were elevated at all ages tested compared with wild-type littermates. At the oldest ages, two out of eight Coch(G88E/G88E) mice had no measurable VsEP. Auditory brainstem response (ABR) thresholds of Coch(G88E/G88E) mice were substantially elevated at 21 months but not at younger ages tested. At 21 months, four of eight Coch(G88E/G88E) mice had absent ABRs at all frequencies tested and two of three Coch(G88E)(/+) mice had absent ABRs at three of four frequencies tested. Distortion product otoacoustic emission amplitudes of Coch(G88E/G88E) mice were substantially lower than Coch(+/+) mice and absent in the same Coch(G88E/G88E) mice with absent ABRs. These results suggest that vestibular function is affected beginning as early as 11 months when cochlear function appears to be normal, and dysfunction increases with age. Hearing loss declines substantially at 21 months of age and progresses to profound hearing loss at some to all frequencies tested. This is the only mouse model developed to date where hearing loss begins at such an advanced age, providing an opportunity to study both progressive age-related hearing loss and possible interventional therapies.