Wegener's granulomatosis: role of environmental exposures.

OBJECTIVE: The etiology of Wegener's granulomatosis (WG) remains unknown. The predominant involvement of the airways and the presence of neutrophilic alveolitis at disease onset have led us to postulate that an inhaled agent may trigger the onset of WG. This study is designed to analyze differences in self-reported environmental exposures between patients with WG and various control populations. METHODS: We conducted a standard interviewer-administered questionnaire case controlled survey of 101 patients with WG, 54 healthy controls, 24 patients with sarcoidosis or idiopathic pulmonary fibrosis, and 45 patients with various inflammatory rheumatologic diseases. We assessed environmental exposures for one year prior to the onset of symptoms or prior to the interview date for healthy controls. RESULTS: Seasonal differences in the onset of WG were not apparent. More than 75% of the patients in all groups noted remarkable environmental exposure to inhaled substances (fumes or particulate matter), within one year prior to disease onset for WG and other diseases or prior to the interview date for healthy controls. Differences between WG and control groups were apparent in several categories of exposure. Statistically significant differences occurred in regard to a vocational exposure to fumes or particulate materials (WG > healthy controls and rheumatic disease controls), residential exposure to particulate materials from construction (WG > pulmonary disease controls) and occupational exposure to pesticides (WG > healthy, pulmonary and rheumatic disease controls). CONCLUSION: This study confirms the absence of seasonal differences in the onset of WG. It also demonstrates high rates of self-reported environmental exposures to inhaled substances in WG and all control populations. It is possible that more significant differences in the quality, quantity and intensity of exposure to inhaled potential precipitants of WG had occurred between groups, but were not detected by our survey. Alternatively, the absence of substantial differences in patients with WG and controls may reflect the more important role of host susceptibility factors.

Rheumatic manifestations of dysproteinemias and lymphoproliferative disorders.

Rheumatic manifestations may be the presenting features of dysproteinemias and lymphoproliferative disorders. Disease or therapy-related complications may mimic a number of primary rheumatic syndromes. This article emphasizes clinical aspects pertaining to prompt diagnosis and therapy.

Drug-induced vasculitis.

Vasculitis resulting from drug use includes a wide variety of clinical and pathologic conditions that are, in general, empirically defined and poorly understood. Further complicating our grasp of these disorders are ambiguous terms such as hypersensitivity vasculitis, allergic vasculitis, leukocytoclastic vasculitis, serum sickness, and others, which are often used interchangeably without clear definition. The clinical picture varies widely from self-limiting to progressive and even fatal illness. These syndromes have now been reported in association with newer classes of therapeutic agents including biologic response modifiers. Vasculitis affecting the central nervous system may be related to a variety of drugs and remains one of the more important syndrome sets within the spectrum of drug-induced vasculitis. These disorders are clinically important, because removal of the offending drug often is associated with regression of the vasculitic condition.

Wegener's granulomatosis.

To manage Wegener's granulomatosis (WG) effectively, the clinician must establish the diagnosis without delay, recognize variability in clinical course and severity, critically monitor disease activity, and anticipate disease-related and treatment-related morbidity. These issues represent the focus of approach to the diagnosis and treatment of WG.

Limitations of invasive modalities in the diagnosis of primary angiitis of the central nervous system.

OBJECTIVE: Rheumatologists are often consulted to evaluate patients suspected of having primary angiitis of the central nervous system (PACNS). The diagnostic process relies heavily on interpreting the results of cerebral angiography and brain biopsy. We have assessed the operating characteristics of those invasive modalities in the diagnosis of PACNS: METHODS: The records of 30 consecutive patients referred for the evaluation of possible PACNS were retrospectively analyzed. Patients were evaluated on clinical grounds, and the diagnostic process was extended accordingly until a reasonable probability of a definable disease was present. All patients had cerebral angiography and/or brain biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were assessed for each of the following diagnostic tests: cerebral angiography, brain biopsy, cerebrospinal fluid (CSF) examination, and magnetic resonance imaging (MRI). RESULTS: The final diagnostic outcomes were: PACNS in 7, lymphoproliferative disease in 4, infection in 4, demyelinating disease in 2, reversible vasospastic disorder in 6, and a variety of other nonvasculitic conditions in 7. Cerebral angiography had less than 30% specificity and PPV for PACNS: Brain biopsy had limited sensitivity and NPV (53% and 70%, respectively). CSF examination and MRI, although sensitive, lacked specificity. CONCLUSION: In patients suspected of having PACNS, the results of invasive diagnostic modalities should be interpreted with caution. Accurate diagnosis should rarely rely on any single study and should only follow careful clinical, radiographic and pathologic correlation.

Treatment of refractory cutaneous lupus erythematosus.

Photoprotection, topical steroids, and hydroxychloroquine are the mainstays of therapy of cutaneous LE. In severe and/or refractory disease, antimalarials remain the drugs of choice, and multiple induction and combination strategies can be employed to achieve optimal results with minimal toxicity. Retinoids, dapsone, clofazimine, and thalidomide are effective but more toxic alternatives. Their use dictates frequent and careful monitoring. Retinoids and thalidomide are teratogenic, and thalidomide is not available in the United States. Results with vitamin E are controversial. Gold and IFN-alpha have unacceptably high risk to benefit ratios. Cytotoxic agents are generally restricted to the patients with concomitant organ-threatening systemic disease.

Evaluation and treatment of central nervous system vasculitis.

Angiitis of the central nervous system (CNS) remains a poorly understood and clinically challenging form of vascular inflammatory disease. Primary angiitis of the CNS (PACNS) has been viewed as a relentless and uniformly fatal disorder if untreated. In addition, recent trends have demonstrated an increasing reliance on angiographic diagnosis without tissue confirmation. It has been suggested that PACNS is clinically more heterogeneous than previously appreciated and may include relatively benign subsets. A reappraisal of diagnostic approaches has suggested caution in the diagnosis of CNS angiitis on purely angiographic grounds. Secondary vasculitis of the CNS is even more heterogeneous. Clinicians involved in the evaluation of patients with presumed CNS vasculitis need to be aware of the clinical spectrum of vascular inflammatory disease within the CNS as well as the strengths and limitations of currently available diagnostic modalities.