trimethoprim--sulfamethoxazole-drug-combination and Granulomatosis-with-Polyangiitis

Infections are associated with secondary forms of vasculitis. However, there is increasing evidence that microbial agents play a role also in primary systemic vasculitides. For a long time it has been noted that Hepatitis B virus (HBV) is involved in polyarteritis nodosa (PAN) although the incidence of HBV-associated PAN seems to decline. Cryoglobulinemic vasculitis has been shown to be strongly associated with Hepatitis C Virus (HCV) infection, but this is most striking in Southern Europe and less in Northern Europe. Different microbial agents have been suggested to influence disease expression in other primary vasculitides but no specific association has been established. In Wegener's Granulomatosis (WG) chronic carriage of Staphylococcus aureus (S. aureus) is associated with a strongly increased risk for relapsing disease. Various pathogenic pathways for this association have been suggested by clinical and experimental observations. Recent studies even suggest that S. aureus derived peptides, amongst others, may induce proteinase 3-ANCA via idiotypic-anti-idiotypic interactions. Treatment with co-trimoxazole in WG localized to the upper airways may result in (temporary) remission of the disease.

Topics: Anti-Infective Agents; Antibodies, Antineutrophil Cytoplasmic; Antigens, Bacterial; Arthritis; Cryoglobulinemia; Europe; Granulomatosis with Polyangiitis; Hepatitis B; Hepatitis B virus; Hepatitis C; Humans; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Age Factors; Anti-Infective Agents; Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Cyclophosphamide; Diagnosis, Differential; Drug Therapy, Combination; Emergencies; Glomerulonephritis; Granulomatosis with Polyangiitis; Hematuria; Humans; Immunosuppressive Agents; Male; Middle Aged; Plasmapheresis; Prednisone; Prognosis; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To date, in the investigation of the role of S. aureus in WG, we face a paradoxical situation. On the one hand, clinical results obtained from treatment of WG patients with co-trimoxazole and studies assessing the impact of S. aureus on disease relapses strongly suggest that this bacterium contributes to disease pathophysiology. On the other hand, laboratory investigation of the possible mechanisms by which S. aureus is involved in WG is scarce, despite the fact that knowledge and tools to study this microorganism are abundant. In the present review, we discuss recent works investigating the possible pathophysiologic contribution of S. aureus to WG. Moreover, we propose a number of possibly relevant pathways of interaction of this bacterium with lymphoid and nonlymphoid cells of the WG host.

Topics: Anti-Infective Agents; Endothelium; Exotoxins; Granulomatosis with Polyangiitis; Humans; Leukocytes; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Anti-Inflammatory Agents; Azathioprine; Cyclophosphamide; Diagnosis, Differential; Drug Therapy, Combination; Follow-Up Studies; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Male; Methotrexate; Methylprednisolone Hemisuccinate; Prednisone; Prognosis; Radiography, Thoracic; Recurrence; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

A diagnosis of Wegener granulomatosis requires granulomatous manifestations in the respiratory tract. With the increasing use of antineutrophil cytoplasmic autoantibodies as a diagnostic tool, Wegener granulomatosis is diagnosed earlier than in the past, and not infrequently when only ear, nose and throat manifestations are present, placing the otorhinolaryngologist in a central role in diagnosis and management. Diagnostic biopsies should be obtained from active lesions in the nose and paranasal sinuses and concomitant infection should be identified. Because of the apparent relation between infection and activation of disease, the management of infections-especially those due to Staphylococcus aureus-requires special attention. The increasing numbers of early cases identified warrants further investigations of whether less toxic treatment regimens will be of advantage in such cases. Medical and surgical treatment of the acute and chronic manifestations presents specific problems because of altered immune competence, prevalent superinfection, and tissue destruction, and is therefore best taken care of by specially dedicated otorhinolaryngologists.

Topics: Ear Diseases; Granulomatosis with Polyangiitis; Humans; Laryngeal Diseases; Mouth Diseases; Nasal Mucosa; Nose Diseases; Paranasal Sinus Diseases; Salivary Gland Diseases; Staphylococcal Infections; Tracheal Diseases; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis

The two principal aims in the treatment of Wegener's granulomatosis (WG) are to limit the extent and severity of permanent organ damage by controlling the disease promptly and to minimize the short- and long-term morbidity that often results from therapy. Remission is considered to be the absence of disease activity in any organ system. Once the disease has been controlled by the initial treatment regimen, which is dictated by the degree of disease severity, the focus of therapy shifts to maintaining disease remission, often with medications less toxic than those used to induce remission. The description of WG treatments in terms analogous to cancer chemotherapy (i.e., those designed to induce remissions and those intended to maintain them) is useful in the formulation of current disease management strategies and in the investigation of new therapies for WG.

Topics: Adrenal Cortex Hormones; Azathioprine; Cyclophosphamide; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Methotrexate; Remission Induction; Trimethoprim, Sulfamethoxazole Drug Combination

Wegener's granulomatosis (WG) is a rare disease among paediatric patients. Chronic otitis media with or without facial nerve dysfunction is a known manifestation of the disease among adults. A case of a 15-year-old boy with WG, whose initial symptoms were acute otitis media and facial nerve paralysis, is presented. The otorhinolaryngological manifestations, as well as diagnostic and current treatment modalities in paediatric patients with WG, are discussed.

Topics: Administration, Oral; Adolescent; Adult; Anti-Infective Agents, Urinary; Anti-Inflammatory Agents; Antineoplastic Agents, Alkylating; Biopsy; Chronic Disease; Cyclophosphamide; Diagnosis, Differential; Drug Therapy, Combination; Ear, Middle; Facial Nerve; Facial Paralysis; Granulomatosis with Polyangiitis; Humans; Injections, Intravenous; Male; Otitis Media; Prednisone; Severity of Illness Index; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Turbinates

Topics: Anti-Infective Agents; Drug Administration Schedule; Granulomatosis with Polyangiitis; Humans; Models, Biological; Respiratory Tract Infections; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

The association of infections and autoimmune disease has been noted by various authors. Several mechanisms have been proposed to explain this, with no current consensus. Wegener's granulomatosis (WG) is an autoimmune disease involving predominantly the pulmonary and renal systems, and is associated with a distinct autoantibody-the anti neutrophil cytoplasmic antibody (ANCA). Although no solid evidence implicates infections in the emergence of WG, direct and circumstantial data suggest this relation. We review this evidence and discuss possible underlying mechanisms. We emphasize the relationship between infections and ANCA, and their role in the maintenance of the 'on-going' inflammatory response.

Topics: Antibodies, Antineutrophil Cytoplasmic; Granulomatosis with Polyangiitis; Humans; Infections; Middle Aged; Neutrophil Activation; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adrenal Cortex Hormones; Granulomatosis with Polyangiitis; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Granulomatosis with Polyangiitis; Humans; Recurrence; Staphylococcal Infections; Trimethoprim, Sulfamethoxazole Drug Combination

Late involvement of the parotid gland in a patient with a limited form of Wegener's granulomatosis is presented. We report the full course of the disease and the difficulties encountered in determining the nature of the parotid enlargement. We discuss the contribution of computerized tomography and ultrasonography to elucidate parenchymal morphologic findings and radioisotope studies to determine the functional capacity of the gland. In cases of Wegener's granulomatosis with salivary symptoms, measurement of salivary gland functional capacity, in addition to the c-ANCA test, may help to monitor disease activity. Despite the rarity of the disease, in cases when granulomatous diseases are considered, it should be recognized that Wegener's granulomatosis may result in salivary gland involvement.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Biomarkers; Cyclophosphamide; Female; Granulomatosis with Polyangiitis; Humans; Parotid Diseases; Parotid Gland; Prednisone; Technetium Tc 99m Mertiatide; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination; Ultrasonography

The clinical manifestations of Wegener's granulomatosis (WG) may be varied and easily overlooked. Awareness of distinguishing signs and symptoms allows early recognition and appropriate management. The body of literature dealing with the various facets of this disorder has grown in the past few years. Development of new diagnostic markers and successful therapies has rekindled interest in this disease. To assure early diagnosis and optimal prognosis the physician must maintain a high index of suspicion for WG. Although introduction of immunosuppressive therapy has dramatically improved the course of this disorder, treatment-related morbidity is often profound.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Biomarkers; Cyclophosphamide; Diagnosis, Differential; Drug Therapy, Combination; Granulomatosis with Polyangiitis; Humans; Male; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

Wegener's syndrome is a granulomatous angiitis with peri or extra-vascular granulomas. The complete form, includes glomerulopathy, pulmonary signs and lesions of the face. Prognosis improved with corticosteroids and immunosuppressors although appropriate administration modalities are still under debate.

Topics: Adrenal Cortex Hormones; Adult; Female; Glomerulonephritis; Granulomatosis with Polyangiitis; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Lung Diseases; Male; Middle Aged; Nose Diseases; Plasma Exchange; Prognosis; Trimethoprim, Sulfamethoxazole Drug Combination

Wegener's granulomatosis is a rare disease of unknown etiology. Until recently it was considered uniformly fatal. Family physicians should be aware of the variable presentations of this disease and keep the diagnosis in mind when faced with a puzzling, chronic, progressive multisystem process. New laboratory markers can lead to earlier diagnosis, and aggressive treatment can improve the prognosis.

Topics: Adult; Biopsy; Clinical Protocols; Cyclophosphamide; Diagnosis, Differential; Family Practice; Female; Granulomatosis with Polyangiitis; Humans; Magnetic Resonance Imaging; Prednisone; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Azathioprine; Biopsy; Cyclophosphamide; Glomerulonephritis; Granulomatosis with Polyangiitis; Humans; Lung; Prednisone; Radiography; Rhinitis; Stomatitis; Trimethoprim, Sulfamethoxazole Drug Combination

The granulomatous vasculitides frequently involve the lung. These syndromes include Wegener's granulomatosis, allergic angiitis and granulomatosis, and the polyangiitis overlap syndrome. Although not a true systemic vasculitis, necrotizing sarcoid granulomatosis also represents a type of pulmonary vasculitis. It is clear that many infectious agents can cause a picture in the lung that can be confused with granulomatous vasculitis and that an infectious process must be ruled out before a diagnosis of pulmonary vasculitis can be established. Pulmonary vasculitis can be associated with the hypersensitivity vasculitides, and pulmonary hemorrhage can be secondary to pulmonary capillaritis. Therapy of the hypersensitivity vasculitides consists of removing the offending antigen and instituting a limited course of corticosteroids. If the vasculitis is secondary to an underlying disease, such as lymphoma, therapy should be directed at the primary disease. Combination therapy with cyclophosphamide and corticosteroids is effective in the systemic vasculitides and the 5-yr survival rate is approximately 90%.

Topics: Adrenal Cortex Hormones; Azathioprine; Behcet Syndrome; Chlorambucil; Connective Tissue Diseases; Cyclophosphamide; Cyclosporins; Drug Combinations; Granuloma; Granulomatosis with Polyangiitis; Hemorrhage; Humans; Lung Diseases; Lymphomatoid Granulomatosis; Respiratory Tract Infections; Sulfamethoxazole; Syndrome; Takayasu Arteritis; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vasculitis; Vasculitis, Leukocytoclastic, Cutaneous

Bacterial and viral respiratory tract infections may trigger relapses in patients with PR3-positive vasculitis. Data have suggested that treatment with co-trimoxazole may be beneficial, because this antibiotic could act by eliminating the offending microbe and thereby stopping the initiating stimulus.. Prospective, randomized, placebo-controlled study of the efficacy of co-trimoxazole given 960 mg thrice weekly for 18 months in preventing relapses in patients with Wegener's granulomatosis (WG) in remission, after treatment with cyclophosphamide and prednisolone was conducted. Relapses and infections were assessed with predefined criteria based on clinical, laboratory, serological, microbiological, and histopathological findings. Sixteen patients were assigned to receive co-trimoxazole and 15 to receive placebo.. Seventy five percent of the patients in the co-trimoxazole group remained in remission at 18 months and 55% of those in the placebo group. A proportional hazard regression analysis identified a positive PR3-ANCA test at the start of treatment, chronic nasal crusting, and Staphylococus aureus infection as risk factors for relapse. Furthermore, the analysis identified treatment with co-trimoxazole as an independent factor associated with prolonged disease-free interval.. Treatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener's granulomatosis in remission.

Topics: Adult; Aged; Anti-Infective Agents; Female; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Prospective Studies; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

Respiratory tract infections may trigger relapses in patients with Wegener's granulomatosis in remission. Uncontrolled data have suggested that treatment with trimethoprim-sulfamethoxazole (co-trimoxazole) may be beneficial.. We conducted a prospective, randomized, placebo-controlled study of the efficacy of co-trimoxazole (800 mg of sulfamethoxazole and 160 mg of trimethoprim) given twice daily for 24 months in preventing relapses in patients with Wegener's granulomatosis in remission during or after treatment with cyclophosphamide and prednisolone. Relapses and infections were assessed with predefined criteria based on clinical, laboratory, and histopathological findings. Patients were evaluated at least once every three months for signs of disease activity, compliance with the treatment regimen, side effects of the therapy, and evidence of infections. Titers of serum antineutrophil cytoplasmic antibodies were measured serially.. Forty-one patients were assigned to receive co-trimoxazole, and 40 to receive placebo. In 8 of the 41 patients in the co-trimoxazole group (20 percent), the drug had to be stopped because of side effects. According to life-table analysis, 82 percent of the patients remained in remission at 24 months, as compared with 60 percent of the patients in the placebo group (relative risk of relapse, 0.40; 95 percent confidence interval, 0.17 to 0.98). There were fewer respiratory tract infections (P = 0.005) and non-respiratory tract infections (P = 0.05) in the co-trimoxazole group than in the placebo group. There were no significant differences in antineutrophil cytoplasmic antibody titers at any time. Proportional-hazards regression analysis identified treatment with co-trimoxazole as an independent factor associated with prolonged disease-free survival and a positive antineutrophil cytoplasmic antibody test at the start of treatment as a risk factor for relapse.. Treatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener's granulomatosis in remission.

Topics: Adult; Aged; Aged, 80 and over; Anti-Infective Agents; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Disease-Free Survival; Double-Blind Method; Female; Granulomatosis with Polyangiitis; Humans; Life Tables; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Recurrence; Respiratory Tract Infections; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We prospectively studied trimethoprim/sulfamethoxazole (T/S) in inducing remission in 'initial phase' Wegener's granulomatosis (WG), and in sustaining remission in generalized WG, in 72 patients in various disease stages. Nineteen patients with initial phase WG received T/S (2 x 960 mg/day). Another 24 patients with generalized WG received the same dose of T/S (group A) and were compared with 21 patients receiving no further treatment after standard therapy (group B). Eight patients were given T/S plus low-dose prednisone (group C). Eleven of 19 patients (58%) with initial phase WG achieved complete or partial remission lasting a median 43 months (range 6-88 months). Of the remaining eight (42%), five showed local disease progression, and three developed generalized WG. In group A (T/S alone, generalized WG), 10/24 (42%) suffered a relapse after a median 13 months (range 4-58 months). In group B (generalized WG, no further treatment) 29% of patients relapsed after a median 22.5 months (range 18-26 months). All eight patients treated with T/S plus low-dose prednisone (group C) suffered serious relapse after 2-24 months. T/S induced long-term remission in > 50% of patients with initial phase WG; however, neither T/S alone nor T/S plus low-dose prednisone sustained remission in generalized WG.

Topics: Adult; Aged; Disease Progression; Female; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Male; Middle Aged; Prednisone; Prospective Studies; Remission Induction; Trimethoprim, Sulfamethoxazole Drug Combination

We assessed the clinical significance of cANCA in relation to the diagnosis and follow-up of Wegener's granulomatosis patients using NephroScholor C-ANC, the ELISA kit for the detection of cANCA. The NephroScholor C-ANC test for cANCA was revealed to be useful for the diagnosis of Wegener's granulomatosis, but slightly less sensitive than the indirect immunofluorescence assay using human neutrophils, which has been in widespread use for the detection of ANCAs. With NephroScholor C-ANC, the cANCA titer can be estimated conveniently and expressed quantitatively. When conventional immunosuppressive therapy with prednisolone and cyclophosphamide was applied, the patients' symptoms subsided as the cANCA titer decreased, and thus it also seemed useful for the follow-up of Wegener's granulomatosis patients. However, a rising ANCA titer during the course of the disease was not always correlated with the occurrence of a relapse as previously reported. Based on these findings, it is not recommended that treatment be changed immediately because of elevation of the ANCA titer alone, and it never seemed too late to increase immunosuppressive therapy, even after a clinical exacerbation was observed. Several treatments other than the conventional immunosuppressive therapy have often been applied for our patients, especially in the limited type of this disease, and these treatments, including sulfamethoxazole-trimethoprim alone, low-dose prednisolone alone, and cyclophosphamide alone, have often been useful. We conclude that the choice of therapy must depend on the severity or the condition of the individual patient, and this therapeutic policy should reduce unnecessary side effects of potentially toxic drugs.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Biomarkers; Cyclophosphamide; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Prednisolone; Trimethoprim, Sulfamethoxazole Drug Combination

Antibiotic prophylaxis is recommended during ANCA-associated vasculitis (AAV) induction. We aimed to describe the frequency, persistence, and factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) use in an adult population sample with granulomatosis with polyangiitis (GPA) treated with rituximab (RTX).. We identified adults with GPA treated with RTX within the Merative™ Marketscan® Research Databases (2011-2020). TMP-SMX prophylaxis was defined as a [Formula: see text] 28-day prescription dispensed within a month of starting RTX. We estimated TMP-SMX persistence, allowing prescription refill gaps of 30 days. Multivariable logistic regression and Cox proportional hazards regression assessed the factors associated with baseline TMP-SMX use and persistence, respectively. Covariates included age, sex, calendar year, insurance type, immunosuppressant use, hospitalization, and co-morbidities.. Among 1877 RTX-treated GPA patients, the mean age was 50.9, and 54% were female. A minority (n = 426, 23%) received TMP-SMX with a median persistence of 141 (IQR 83-248) days. In multivariable analyses, prophylaxis was associated with prednisone use in the month prior to RTX ([Formula: see text] 20 mg/day vs none, OR 3.96; 95% CI 3.0-5.2; 1-19 mg/day vs none, OR 2.63; 95% CI 1.8-3.8), and methotrexate use (OR 1.48, 95% CI 1.04-2.1), intensive care (OR 1.95; 95% CI 1.4-2.7), and non-intensive care hospitalization (OR 1.56; 95% CI 1.2-2.1) in the 6 months prior to RTX. Female sex (OR 0.63; 95% CI 0.5-0.8) was negatively associated with TMP-SMX use.. TMP-SMX was dispensed to a minority of RTX-treated GPA patients, more often to those on glucocorticoids and with recent hospitalization. Further research is needed to determine the optimal use and duration of TMP-SMX prophylaxis following RTX in AAV.

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Female; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Retrospective Studies; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination; United States

To identify the role of Staphylococcus aureus (SA) or its intracellular small-colony variant phenotype (SCV) with co-trimoxazole (CTX) or ANCA-associated vasculitis (AAV) activity.. All consecutive AAV patients with granulomatosis with polyangiitis (GPA), eosinophilic GPA or microscopic polyangiitis, followed at the French National Vasculitis Referral Center (09/2012-05/2013), and hospitalized non-AAV controls, exclusively for SA/SCV carriage comparisons, were enrolled. All had bilateral anterior nasal swab cultures. Nasal SA or SCV carriage was determined and associations with relapse(s), BVAS, ANCA-positivity, anti-staphylococcal and immunosuppressant use, were analysed ⩾4 years post-inclusion.. Nasal SA carriage rates did not differ among AAVs (P = 0.53): GPA (24/80; 30%), EGPA (7/28; 25%) and microscopic polyangiitis (3/11; 27.3%); and the rate was less frequent in controls than in GPA patients not taking CTX (P = 0.04). AAV patients taking CTX prophylaxis had less nasal SA carriage (8.7% vs 36.2%; P = 0.02). Nasal SA carriage or CTX use did not modify relapse rates, BVAS or ANCA-positivity at inclusion or during follow-up. Nasal SCV carriage, found in 15/207 (7.2%) patients, was similar for GPA (10/24; 41.7%), microscopic polyangiitis (2/7; 28.6%) and eosinophilic GPA (2/3; 66.7%), but higher (P = 0.02) than controls (1/14; 7.1%). SCV carriage by AAV groups did not modify relapse rates or ANCA positivity at inclusion or during follow-up; a trend towards higher BVAS was observed only for anti-PR3 ANCA patients.. Nasal SA or SCV carriage was comparable among AAVs but more frequent than in controls. Nasal SA or SCV carriage and CTX use did not modify AAV relapse rates.

Topics: Adult; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibiotic Prophylaxis; Churg-Strauss Syndrome; Female; France; Granulomatosis with Polyangiitis; Humans; Male; Microscopic Polyangiitis; Middle Aged; Nasal Cavity; Phenotype; Prospective Studies; Recurrence; Secondary Prevention; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Agammaglobulinemia; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antirheumatic Agents; Churg-Strauss Syndrome; Delphi Technique; Duration of Therapy; Granulomatosis with Polyangiitis; Humans; Immunocompromised Host; Influenza Vaccines; Influenza, Human; Maintenance Chemotherapy; Microscopic Polyangiitis; Neutropenia; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia, Pneumocystis; Practice Guidelines as Topic; Recurrence; Rituximab; Trimethoprim, Sulfamethoxazole Drug Combination; United Kingdom

Gingival pathology is a daily presentation, however a small number of systemic conditions can manifest similar to a common gingival condition and have fatal results. Dentist referred 56-year-old woman to Oral and Maxillofacial Surgery department with a 2-week medical history of gingival bleeding not responding to local measures. Biopsy showed eosinophilic infiltrate and vasculitis, and blood tests showed positive markers including cytoplasmic antineutrophil cytoplasmatic antibodies. Granulomatosis with polyangiitis is a rare disease affecting the respiratory tract, blood vessels and kidneys. Oral lesions are rarely the primary presenting feature. When left untreated, most cases are fatal within a year of diagnosis. The diagnosis can only be made when certain criteria are found, including granular oral lesions exhibiting an eosinophilic inflammatory infiltrate on biopsy. With 5% of cases showing intraoral lesions as the primary feature, it is essential that dentists have the knowledge of this rare disease to refer and not to treat as a common gingival condition.

Topics: Aftercare; Anti-Bacterial Agents; Antibodies, Antineutrophil Cytoplasmic; Biopsy; Dentists; Diagnosis, Differential; Eosinophils; Female; Giant Cells, Foreign-Body; Gingival Diseases; Glucocorticoids; Granulomatosis with Polyangiitis; Hemorrhage; Humans; Middle Aged; Oral Ulcer; Prednisolone; Rare Diseases; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Granulomatosis with polyangiitis (GPA) is more frequent in Northern rather than Southern countries. Very few studies have been conducted in Africa. We have performed a retrospective descriptive study including clinical and laboratory profiles of 30 Tunisian GPA patients seen at the department of Internal Medicine of the University Hospital of la Rabta from 2000 to 2014. Mean age at initial GPA diagnosis was 46±12 years, and the average number of months between the onset of symptoms and diagnosis was 25. Seventeen (56%) were male, and 13 (44%) were female. Ear/nose/throat involvement occurred in 83%. Lung and renal involvement were observed in respectively 70% and 56% followed by mucocutaneous (50%), neurological (50%), ocular (33%), vascular (20%), ureteral (16%), and cardiac involvement in 10%. Cytoplasmic pattern-antineutrophil cytoplasmic antibodies (ANCA) was detected in 27 (90%) patients. Induction therapy consisted of intravenous cyclophosphamide pulses in 27 patients (90%) and oral methotrexate in 3 patients (10%). Trimethoprime-sulfamethoxazole was used in 26 patients (86%). Maintenance therapy consisted of azathioprine in 17 cases and methotrexate in 13 cases. Relapses occurred in 36%. Eighteen patients had favorable outcome and 12 died. Our patients had a distinct phenotype with high prevalence of pleural involvement, lymph node enlargement, sensorimotor neuropathy and ureter stenosis. ENT symptoms were less frequent as inaugural presentation. Overall 2-year survival was 60%.

Topics: Adult; Anti-Bacterial Agents; Antibodies, Antineutrophil Cytoplasmic; Azathioprine; Biomarkers; Cyclophosphamide; Drug Therapy, Combination; Female; Follow-Up Studies; Granulomatosis with Polyangiitis; Hospitals, University; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Prevalence; Recurrence; Retrospective Studies; Survival Rate; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tunisia

Granulomatosis with polyangiitis is an uncommon condition characterised by vasculitis and associated granuloma formation with a highly specific autoantibody, namely proteinase 3-anti-neutrophil cytoplasmic antibody (ANCA). The respiratory tract and kidneys are the organ systems most often involved. Symptoms can be non-specific, and isolated hearing loss can predate other symptoms by months, leading to lengthy delays in diagnosis and treatment. Left untreated, hearing loss can be irreversible, and therefore early diagnosis is crucial. We present a case study of severe hearing impairment in an attempt to raise awareness of ear involvement as an early feature of this unusual condition.

Topics: Adult; Azathioprine; Cyclophosphamide; Diagnosis, Differential; Diphosphonates; Female; Granulomatosis with Polyangiitis; Hearing Loss; Humans; Prednisolone; Proton Pump Inhibitors; Toothache; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Cyclophosphamide; Drug Therapy, Combination; Female; Granulomatosis with Polyangiitis; Humans; Middle Aged; Prednisone; Risk Assessment; Severity of Illness Index; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, in children is an uncommon chronic organ- and life-threatening systemic vasculitis that may share at time of initial presentation a number of clinical features in common with Henoch-Schönlein purpura (HSP), a very common and comparatively benign form of childhood vasculitis. Diagnosis of GPA requires a high index of suspicion, and antineutrophil cytoplasmic antibody tests along with tissue biopsy are helpful tools for diagnosis. We report 2 patients with GPA masqueraded as HSP at time of initial presentation. Both patients presented with nonthrombocytopenic purpura on lower extremities, in addition to abdominal pain, and/or microscopic hematuria and fulfilled both the American College of Rheumatology and the Pediatric Rheumatology European Society classification criteria for HSP. Both patients eventually developed significant renal and pulmonary disease and were diagnosed with GPA. We aim to raise awareness of such atypical presentations of GPA to avoid delayed management.

Topics: Abdominal Pain; Anti-Infective Agents; Antibodies, Antineutrophil Cytoplasmic; Azathioprine; Child; Cyclophosphamide; Diagnosis, Differential; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Granulomatosis with Polyangiitis; Hematuria; Humans; IgA Vasculitis; Immunosuppressive Agents; Male; Plasmapheresis; Proteinuria; Trimethoprim, Sulfamethoxazole Drug Combination

Wegener's granulomatosis (WG) is a necrotizing granulomatous vasculitis involving the nose, paranasal sinuses, lungs, and kidneys. Ocular involvement can occur in about 50% of cases. There are very few reports of WG with orbital inflammation and exorbitism. We report a case of a female patient who presented with exorbitism related to orbital inflammation secondary to WG, with renal involvement. A 29-year-old woman with a previous history of recurrent pan-sinusitis presented with bilateral exophthalmos and renal failure with rapidly progressive glomerulonephritis. Computed tomography showed extensive bilateral soft tissue in the retro-orbital area. Immunologic tests showed the presence of type-C anti-neutrophil cytoplasmic antibodies and renal biopsy revealed pauci immune crescentic glomerulonephritis. The patient was treated with corticosteroids and pulses of cyclophosphamide followed by azathioprine and trimethoprim-sulfamethoxazole. After a follow-up of 10 months, the renal outcome was favorable with improvement of renal function but there was persistence of exorbitism and loss of visual function. Our case suggests that WG should be considered in the differential diagnosis of persistent bilateral exophthalmos. Prompt recognition of this early manifestation is important for the institution of early treatment.

Topics: Adrenal Cortex Hormones; Adult; Anti-Infective Agents; Anti-Inflammatory Agents; Azathioprine; Cyclophosphamide; Exophthalmos; Female; Glomerulonephritis; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents; Biopsy; Breast Neoplasms; Cyclophosphamide; Female; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Adrenal Cortex Hormones; Anti-Infective Agents; Arthralgia; Cyclophosphamide; Diagnosis, Differential; Fatigue; Female; Fever; Glomerulonephritis; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Muscle Weakness; Pallor; Renal Dialysis; Stomatitis, Aphthous; Trimethoprim, Sulfamethoxazole Drug Combination

Wegener's granulomatosis (WG) is a primary systemic vasculitis with characteristic clinical manifestations from upper airways, lungs, and kidneys. Subglottic stenosis is one of the local symptoms which may occur independently or in association with involvement of other organs.. We present a patient with systemic WG positive for C-ANCA. Regression of pulmonary changes was achieved with induction therapy but the patient developed subglottic stenosis. Endotracheal dilation was partly successful, so systemic treatment had to be reintroduced to inhibit the activity of the disease.. The problem of localized organ lesions in the course of a systemic disease is discussed. It is important to distinguish between signs of active disease requiring systemic therapy and organ lesions which demand a localized approach.

Topics: Adolescent; Cyclophosphamide; Drug Therapy, Combination; Granulomatosis with Polyangiitis; Humans; Injections, Intravenous; Laryngostenosis; Male; Methylprednisolone; Propranolol; Trimethoprim, Sulfamethoxazole Drug Combination

We present a patient with Morbus Wegener and crescentic glomerulonephritis. Treatment with cyclophosphamide and prednisolone resulted in the disappearance of signs and symptoms of systemic inflammation. However, renal function deteriorated. Renal biopsy showed evidence of continuing capillary necrosis. Renal function improved with added plasmapheresis treatment. This case report illustrates that in patients with vasculitis necrotizing glomerulonephritis may remain active despite immunosuppressive therapy, even in the absence of extrarenal disease activity.

Topics: Aged; Cyclophosphamide; Disease Progression; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Kidney Diseases; Male; Prednisolone; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Wegener's granulomatosis is described by the Chapel Hill nomenclature (1994) as a systemic necrotizing vasculitis affecting small to medium-sized vessels. Cytoplasm-labeling antineutrophil cytoplasmic autoantibodies (cANCA) directed against proteinase 3 (PR3) are detected in the sera of approximately 90% of patients. Reported incidence varies from 2 to 12 cases/million inhabitants/year and prevalence from 24 to 157 cases/million inhabitants, depending on the series. While still rare, incidence seems to have increased slightly over the past few decades. Most new cases involve adults aged 45-60 years. Many of the immune mechanisms involved in its pathogenesis have been identified. These involve cANCA as well as neutrophils, various lymphocyte subtypes, activation molecules, and cytokines. Genetic and environmental factors have been observed in some cases. However, the precise causes of the disease and of the initial immune process leading to cANCA production remain unknown. The most characteristic clinical manifestations are involvement of the upper and lower respiratory tracts and glomerulonephritis. Diffuse/systemic forms may be clinically distinguished from localized/limited forms: the former are mainly associated with vasculitis, and the latter with granulomatous inflammation. Diagnosis relies largely on the combination of characteristic clinical symptoms and cANCA anti-PR3, but histological confirmation should always be obtained when biopsy of affected organs is feasible and safe. Kidney biopsy is particularly useful in cases with renal manifestations, because it also provides some prognostic information. Current recommendations for treatment of systemic forms call first for an induction phase that combines corticosteroids and intravenous cyclophosphamide; the first three pulses are given every 2 weeks and then every 3 weeks until remission is achieved, followed by a maintenance phase with a less toxic immunosuppressant. The optimal duration of this regimen has not yet been determined, but it must certainly not be less than 18 months. Continuation of cotrimoxazole for two additional years is advised once immunosuppressants have been withdrawn. Remission is obtained in more than 85% of the cases to date, but the high relapse rate remains a matter of concern: approximately half of all patients will relapse within the five years following diagnosis. Promising new therapeutic agents, including rituximab, anti-TNF-alpha, and abatacept, are currently under e

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Infective Agents; Antibodies, Antineutrophil Cytoplasmic; B-Lymphocytes; Child; Dendritic Cells; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Male; Middle Aged; Prognosis; Sex Factors; T-Lymphocytes; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

A 54-year-old man, who was suspected to suffer from multi-drug resistant lung abcess, was admitted to our hospital. Chest computed tomography (CT) scan showed large cavitary mass in right S6 and nodules in left S1+2 and S10. No abnormal findings were detected without raised immunoglobulin E (IgE) and C-reactive protein (CRP). Anti-neutrophil cytoplasmic antibody (ANCA) was repeatedly negative. We couldn't make a diagnosis by percutaneous biopsy. Finally we performed open lung biopsy of left lung, and Wegener's granulomatosis was diagnosed at last He improved immediately after treatment with prednisolone, cyclophosphamide and sulfamethoxazole-trimethoprim. ANCA-negative Wegener's granulomatosis should be considered when we diagnose multiple pulmonary nodules.

Topics: Antibodies, Antineutrophil Cytoplasmic; Biomarkers; Biopsy; Cyclophosphamide; Diagnosis, Differential; Drug Therapy, Combination; Granulomatosis with Polyangiitis; Humans; Lung; Male; Middle Aged; Prednisolone; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

A 69-year-old woman was admitted to because of bloody sputum. Chest CT showed some nodules. The patient was seronegative for PR3-ANCA. One month after the admission, these shadows vanished with no medication. She was asymptomatic for one and a half years, and then she complained of cough again. Multiple nodules were seen on chest CT again. She was admitted, and surgical biopsy by video-assisted thoracoscopic surgery was performed. She was diagnosed to have a limited form of Wegener's granulomatosis. Multiple shadows vanished without medication, again. Administration of sulfamethoxazole-trimethoprim was started and there has been no relapse.

Topics: Aged; Anti-Infective Agents; Antibodies, Antineutrophil Cytoplasmic; Female; Granulomatosis with Polyangiitis; Humans; Radiography, Thoracic; Solitary Pulmonary Nodule; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Wegener granulomatose is an granulomatous necrotisant vasculitis of unknown ethiology that can affect in a classical form the superior and inferior respiratory tract and kidney. The possibility that the illness is limited to the ENT sphere together to a good accessibility for the biopsy of the nasal fossae and sinus usually convert the ENT in the first specialist for the diagnosis of the illness. It is a systemic illness with a frequent and important ENT expression. We have he possibility to establish an earlier diagnosis with prognostic implications in those patients with ENT clinic. So these patients can benefit the treatment with Cotrimoxazol. We have done a revision of the patients affected of Wegener granulomatose with ENT clinic, treated in the last ten years in our Hospital. We present 9 cases, exposing the age of diagnosis, the initial data, the topographic extension along the illness, the diagnostic methods and the treatment and evolution.

Topics: Antifungal Agents; Diagnosis, Differential; Female; Granulomatosis with Polyangiitis; Humans; Lung Diseases; Male; Middle Aged; Staphylococcal Infections; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

In order to study the characteristic of Wegener granulomatosis in otorhinolaryngology.. We investigated and treated 6 patients.. Five cases were remission, 1 case died.. The feathers of Wegener granulomatosis in otorhinolaryngology have nothing in common with each other, the characteristic of clinic is complicate, cyclophosphamide deltasone and co-trimoxazole are effective.

Topics: Adult; Anti-Infective Agents; Antineoplastic Agents, Alkylating; Cyclophosphamide; Drug Therapy, Combination; Female; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Otorhinolaryngologic Diseases; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Granulomatosis with Polyangiitis; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

We report a case of severe Wegener's granulomatosis that caused end-stage renal failure and recurrent flares of sinusitis and pulmonary manifestations. To avoid the cumulative toxicity of iterative treatments with cyclophosphamide pulses and glucocorticoids, treatment with cyclosporine as a single agent was instituted in the early phase of the third relapse, before any pulmonary involvement. Cyclosporine enabled rapid control of the disease and induced a complete remission of more than 30 months.

Topics: Adult; Anti-Infective Agents, Urinary; Anti-Inflammatory Agents; Antibodies, Antineutrophil Cytoplasmic; Azathioprine; Cyclophosphamide; Cyclosporine; Drug Administration Schedule; Drug Therapy, Combination; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Male; Prednisone; Remission Induction; Secondary Prevention; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adjuvants, Immunologic; Administration, Oral; Anti-Infective Agents; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Controlled Clinical Trials as Topic; Cyclophosphamide; Drug Therapy, Combination; Follow-Up Studies; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Isoxazoles; Leflunomide; Male; Methotrexate; Middle Aged; Multicenter Studies as Topic; Prednisolone; Prognosis; Remission Induction; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Wegener's granulomatosis (WG) is a systemic granulomatous vasculitis that typically affects the upper airways, lungs and kidneys. Lymphadenopathy is rare in patients with WG. Here, we present the first case of WG whose initial manifestation was superficial lymphadenopathy (i.e. supraclavicular and axillary lymphadenopathy). One year after the initial presentation, a mass appeared in the lung. Biopsy specimens obtained from supraclavicular lymph nodes and lung demonstrated granulomatous vasculitis. This patient was negative for classic antineutrophil cytoplasmic antibodies (c-ANCA). Treatment with glucocorticoids, cyclophosphamide and trimethoprim-sulfamethoxazole has induced complete remission.

Topics: Aged; Axilla; Clavicle; Cyclophosphamide; Diagnosis, Differential; Drug Therapy, Combination; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Lung; Lymph Nodes; Lymphatic Diseases; Male; Prednisolone; Radiography, Thoracic; Tomography, X-Ray Computed; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Female; Granulomatosis with Polyangiitis; Humans; Paranasal Sinus Diseases; Radiography; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

We present a case of Wegener's granulomatosis (WG) that responded to antituberculous drugs. A 44-year-old woman with multiple nodules on chest radiograph received a diagnosis of pulmonary tuberculosis because open-lung biopsy specimens showed caseous granulomas. Her chest shadows underwent repeated resolution after the start of antituberculous treatment, and relapse after the cessation of the drugs. Antineutrophil cytoplasmic antibody was positive (14 enzyme-linked immunosorbent assay units), and the second lung biopsy specimens showed necrotizing granulomas and vasculitis without pathogenic organisms. Thus, the patient received a diagnosis of WG and was successfully treated with trimethoprim/sulfamethoxazole 10 years after her initial evaluation. Antituberculous drugs were effective in this case of WG.

Topics: Adult; Anti-Infective Agents; Antitubercular Agents; Female; Granulomatosis with Polyangiitis; Humans; Radiography; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Wegener's granulomatosis (WG) has two different clinical phases: the initial phase and generalized phase. In patients with generalized WG, both steroids and cyclophosphamide have generally been used. We report a case of generalized WG that was temporarily, but successfully treated with sulfamethoxazole-trimethoprim (S/T) alone. S/T therapy reduced the elevated levels of soluble IL-2 receptor and IL-6 in parallel with improvement of the patient's symptoms and urinary protein excretion. In view of the high incidence of lethal adverse effects of cytotoxic drugs, S/T monotherapy may be worth trying not only for initial phase WG but also for generalized WG with careful follow-up when the patient is not acutely ill.

Topics: Aged; Anti-Infective Agents; Cytokines; Drug Combinations; Female; Granulomatosis with Polyangiitis; Humans; Remission Induction; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Female; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Methylprednisolone; Middle Aged; Sjogren's Syndrome; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

To assess the incremental cost-effectiveness of 3 Pneumocystis carinii pneumonia (PCP) prophylaxis strategies in patients with Wegener's granulomatosis (WG) receiving immunosuppressive therapies: 1) no prophylaxis; 2) trimethoprim/sulfamethoxazole (TMP/SMX) 160 mg/800 mg 3 times a week, which is discontinued if patients experience an adverse drug reaction (ADR); and 3) TMP/SMX 160 mg/800 mg 3 times a week, which is replaced by monthly aerosolized pentamidine (300 mg) if patients experience an ADR.. A Markov state-transition model was developed to follow a hypothetical cohort of WG patients over their lifetimes starting from the time of initial exposure to the immunosuppressive therapy. The effect of PCP prophylaxis on life expectancy, quality-adjusted life expectancy, average discounted lifetime cost (ADLC), and incremental cost-effectiveness was estimated based on data obtained from a literature review. Direct medical costs were examined from a societal perspective, and costs and benefits were discounted at 3% annually.. No prophylaxis resulted in a life expectancy of 13.36 quality-adjusted life years (QALY) at an ADLC of $4,538. In comparison, prophylaxis with TMP/ SMX alone increased the QALY to 13.54 and was cost saving, with an ADLC of $3,304. The addition of pentamidine in patients who had an ADR to TMP/SMX resulted in 13.61 QALY, with an ADLC of $7,428. Compared with TMP/SMX alone, TMP/SMX followed by pentamidine increased the QALY by 0.07 at an incremental cost of $58,037 per QALY. Both TMP/SMX alone and TMP/SMX followed by pentamidine prophylaxis strategies dominated the no prophylaxis strategy until the incidence of PCP fell below 0.2% and 2.25%, respectively. Institution of pentamidine therapy for patients with a TMP/SMX ADR increased quality-adjusted life expectancy compared with that with TMP/ SMX alone until the incidence of PCP rose above 7.5%.. Prophylaxis using TMP/SMX alone increased life expectancy and reduced cost for patients with WG receiving immunosuppressive therapy. Replacing TMP/SMX with monthly aerosolized pentamidine in cases of ADR further increased life expectancy, although at an increased cost.

Topics: Adult; Anti-Infective Agents; Cost-Benefit Analysis; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Life Expectancy; Pneumonia, Pneumocystis; Trimethoprim, Sulfamethoxazole Drug Combination

Because of manifestation of Wegener's granulomatosis in the upper respiratory tract the ENT-specialist is often initially involved in diagnosis. Recent research results suppose the chronic nasal carriage of Staphylococcus aureus triggering relapse rate in Wegener's granulomatosis. The adequate therapy of this bacteria as chronic nasal carriage may reduce the number of relapses in patients with Wegener's granulomatosis in remission.. An illustrative case report shows the positive effect of prolonged treatment with cotrimoxazole in a 49-year-old male with a second relapse of Wegener's granulomatosis.. The prolonged treatment of cotrimoxazole reduced the dose of cyclophosphamid and glucocorticoids which show long-term side effects.. 15 years ago a positive effect of cotrimoxazole to Wegener's granulomatosis was discussed. Later immunological and clinical studies confirmed this fact. Prolonged treatment with cotrimoxazole seems to reduce the number of relapses in patients with this chronic disease. Corresponding with our case reduction of the systemic therapy with cyclophosphamid and glucocorticoids is possible.

Topics: Cyclophosphamide; Drug Therapy, Combination; Glucocorticoids; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Prednisolone; Recurrence; Rhinitis; Trimethoprim, Sulfamethoxazole Drug Combination

Wegener's granulomatosis, the most common of the pulmonary granulomatous vasculitides, may affect virtually any organ. Complications resulting from chronic cytotoxic therapy have led to novel treatment strategies. These alternative therapeutic modalities are promising, but additional studies are required to define their roles.

Topics: Adolescent; Adult; Anti-Infective Agents; Azathioprine; Cyclophosphamide; Female; Folic Acid Antagonists; Granulomatosis with Polyangiitis; Humans; Immunoglobulins, Intravenous; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Photomicrography; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

We treated a patient with an atypical presentation of Wegener's granulomatosis (WG) with dural involvement as the initial clinical manifestation. A 37-year-old man had a dural lesion without lower respiratory tract or renal manifestations in the initial clinical course. His only initial symptom was headache, and at disease onset computed tomography (CT) and magnetic resonance imaging (MRI) of the head revealed bilateral abnormal subdural masses. The diagnosis of WG was made based on the results of needle biopsy of the nasal polyps and the finding of positive circulating antineutrophil cytoplasmic antibodies (c-ANCA). He achieved remission on daily prednisone and cyclophosphamide with the later addition of sulfamethoxazole-trimethoprim.

Topics: Adult; Antibodies, Antineutrophil Cytoplasmic; Autoimmune Diseases; Biopsy; Cyclophosphamide; Dura Mater; Granulomatosis with Polyangiitis; Headache; Hematoma, Subdural; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Nasal Polyps; Prednisone; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Granulomatosis with Polyangiitis; Humans; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

Two patients are presented with Wegener's granulomatosis (WG) and lower respiratory tract infections with Staphyloccus aureus (SA). It is posulated that there is a relationship between the infection and the induction or relapse of the disease. We suggest that bronchoalveolar lavages should be performed in cases of suspected WG to identify SA-infections. The co-existence of WG and SA support the reported beneficial effects of sulfamethoxazole/trimethoprim, but needs further evaluation in patients with and without SA-infection of the airways.

Topics: Anti-Bacterial Agents; Bronchoalveolar Lavage Fluid; Colony Count, Microbial; Female; Granulomatosis with Polyangiitis; Humans; Middle Aged; Nose; Recurrence; Respiratory Tract Infections; Sputum; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Anti-Infective Agents; Cyclophosphamide; Drug Therapy, Combination; Female; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Cyclophosphamide; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Prednisolone; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Cyclophosphamide; Ear; Endoscopy; gamma-Globulins; Granulomatosis with Polyangiitis; Humans; Kidney; Lung; Prednisolone; Tracheostomy; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Biopsy; Diagnosis, Differential; Granulomatosis with Polyangiitis; Humans; Lung; Male; Tomography, X-Ray Computed; Triamcinolone Acetonide; Trimethoprim, Sulfamethoxazole Drug Combination

We report a case of Wegener's granulomatosis (WG), localised to the upper aerodigestive tract, which presented as an unusual form of hyperplastic gingivitis in a 36-year-old female. The clinical, serological and histopathological findings are described. The resemblance of the affected gums to over-ripe strawberries is emphasised, in order to draw attention to this characteristic oral manifestation of a rare and potentially life-threatening condition. The response to co-trimoxazole as sole therapy is noted.

Topics: Adult; Female; Gingival Hyperplasia; Gingivitis; Granulomatosis with Polyangiitis; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Treatment and outcome of 111 patients who fell ill with Wegener's granulomatosis (WG) between 1966 and 1990 were analysed retrospectively. Two regimens of treatment were distinguished: "conventional" treatment, i.e. daily application of cyclophosphamide/corticosteroids (FAUCI scheme) or azathioprine/corticosteroids or corticosteroids alone, and "stage-adapted" treatment, characterized by change of different treatments (e.g. cyclophosphamide pulse therapy, cotrimoxazole) according to the extent and activity of disease. In patients who received stage-adapted treatment, exacerbations occurred significantly more frequent than in conventionally treated patients, while lethal outcome was much more frequent in conventionally treated patients.

Topics: Adrenal Cortex Hormones; Azathioprine; Cyclophosphamide; Drug Therapy, Combination; Female; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Remission Induction; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

Since 1985, a number of reports have highlighted the effectiveness of a short course of sulfamethoxazole-trimethoprim as an adjuvant to immunosuppressive drugs in the treatment of Wegener's granulomatosis. We report our experience with long-term sulfamethoxazole-trimethoprim therapy in patients with Wegener's granulomatosis. We describe recent advances in the pathogenesis of Wegener's granulomatosis, suggest a complementary mechanism of action of sulfamethoxazole-trimethoprim, and advocate long-term sulfamethoxazole-trimethoprim therapy as a treatment option in Wegener's granulomatosis.

Topics: Adult; Aged; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Treatment and outcome of 111 patients who fell ill with Wegener's granulomatosis (WG) between 1966 and 1990 were analysed retrospectively. The mean observation time after diagnosis had been 47 (1-288) months. At the time of diagnosis 37 patients suffered from locoregional symptoms only, whereas the disease was generalised in 74 patients. Two regimes of treatment were differentiated: "conventional" treatment, i.e. daily application of cyclophosphamide/prednisolone (FAUCI scheme) or azathioprine/prednisolone or prednisolone alone, and "stage-adapted" treatment, characterised by change of different treatments (e.g. cyclophosphamide pulse therapy, cotrimoxazole) according to the extent and activity of disease. In patients who received stage-adapted treatment, relapses occurred significantly more frequently than in conventionally treated patients. On the other hand, lethal outcome was much more frequent in conventionally treated patients.

Topics: Adult; Aged; Azathioprine; Cyclophosphamide; Cyclosporine; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Male; Methotrexate; Methylprednisolone; Middle Aged; Prednisolone; Quality of Life; Retrospective Studies; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Ophthalmic involvement may be noted in < or = 58% of Wegener's granulomatosis cases, scleritis being one of the most frequent and potentially devastating manifestations. Cytotoxic immunosuppressive drug therapy is effective treatment for this disorder but potentially highly toxic. Recent uncontrolled and anecdotal reports have suggested a possible therapeutic role for a much less toxic agent, trimethoprim/sulfamethoxazole, in limited Wegener's granulomatosis. We report a patient who had a conjunctival nodule and scleritis. Biopsy of the nodule suggested Wegener's granulomatosis, confirmed serologically with serum anti-neutrophil cytoplasmic antibody (ANCA) testing. Treatment with oral trimethoprim/sulfamethoxazole was successful. Clinical response was paralleled by normalization of serial anti-neutrophil cytoplasmic antibody titers. This case is the first well-documented ophthalmologic report of limited Wegener's granulomatosis responding to trimethoprim/sulfamethoxazole and adds to the body of literature suggesting a potential role for this drug in selected cases of limited Wegener's granulomatosis.

Topics: Administration, Oral; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Biomarkers; Conjunctival Diseases; Female; Granulomatosis with Polyangiitis; Humans; Immunoglobulin G; Middle Aged; Scleritis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Granulomatosis with Polyangiitis; Humans; Male; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Granulomatosis with Polyangiitis; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Female; Granulomatosis with Polyangiitis; Humans; Middle Aged; Remission Induction; Trimethoprim, Sulfamethoxazole Drug Combination

We describe a patient with Wegener's granulomatosis (WG) who developed as the only pulmonary manifestation a severe proximal bronchial stenosis despite conventional treatment with steroids and oral cyclophosphamide. The patient subsequently responded to a combined therapy with intravenous (IV) cyclophosphamide and oral cotrimoxazole. We stress the rarity of bronchial involvement in WG and discuss the role of IV cyclophosphamide and cotrimoxazole in the management of this disease.

Topics: Administration, Oral; Adult; Cyclophosphamide; Drug Therapy, Combination; Female; Granulomatosis with Polyangiitis; Humans; Injections, Intravenous; Pulmonary Valve Stenosis; Tomography, X-Ray Computed; Trimethoprim, Sulfamethoxazole Drug Combination

A 44-year-old man with nasal and respiratory symptoms combined with positive serum antibodies to neutrophil cytoplasmic antigens (ANCA) suggestive of Wegener's granulomatosis was treated with antibacterial agents. Complete clinical response was achieved with co-trimoxazole, and the titer of ANCA declined. After a 12-month treatment period, the patient contracted fever and respiratory symptoms and fatigue again, and he had proteinuria and hematuria. After the institution of conventional treatment with oral prednisolone and cyclophosphamide, a favorable response was achieved. Wegener's-like granulomatosis is difficult to diagnose at its early stage, but the presence of ANCA may be helpful. We suggest that co-trimoxazole should be considered as a first-line treatment, under careful supervision, for young patients whose disease is limited to the respiratory organ.

Topics: Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Ciprofloxacin; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Radiography; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adult; Aged; Aged, 80 and over; Combined Modality Therapy; Creatinine; Cyclophosphamide; Cyclosporine; Female; Granulomatosis with Polyangiitis; Humans; Kidney Diseases; Lung Diseases; Male; Middle Aged; Plasmapheresis; Prednisolone; Retrospective Studies; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Sulfamethoxazole-trimethoprim may be an alternative or adjunctive treatment for Wegener's granulomatosis, as suggested by our experience with six patients. Two had limited Wegener's granulomatosis; one of these achieved remission with sulfamethoxazole-trimethoprim alone, and the second achieved remission with sulfamethoxazole-trimethoprim and prednisone. Four patients presented with sinus, pulmonary, and renal involvement. One patient initially treated with sulfamethoxazole-trimethoprim developed worsening renal function requiring cytotoxic therapy. Two patients initially treated with cytotoxic agents achieved remission coincident with the addition of sulfamethoxazole-trimethoprim for persistent sinus symptoms. One patient had relapse of pulmonary symptoms after achieving and maintaining a remission during treatment with sulfamethoxazole-trimethoprim alone. This experience suggests that sulfamethoxazole-trimethoprim may be an effective treatment for some patients with Wegener's granulomatosis and may be the only agent required. Patients require careful follow-up and still may need cytotoxic therapy.

Topics: Adult; Drug Combinations; Female; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Remission Induction; Trimethoprim, Sulfamethoxazole Drug Combination

During the last 3 years 34 patients with Wegener's granulomatosis (W. G.) were treated 37 times with co-trimoxazole (Co-trim). In 10 patients with locoregional disease the progression of W. G. could be stopped in each case. In 27 cases (24 patients) with generalized W. G. in complete remission achieved with cyclophosphamide and prednisolone (Cyc/Pred) a relapse occurred in more than 50% (14/27) of the cases.

Topics: Granulomatosis with Polyangiitis; Humans; Prospective Studies; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination

Two cases of Wegener's granulomatosis presenting with prostatic involvement are described and compiled with the five previously detailed cases. Each of these patients presented with obstructive symptoms, proteinuria, leukocyturia, and hematuria. The urinary sediment normalized with treatment of the underlying granulomatous vasculitis. Wegener's granulomatosis is a rare cause of prostatic obstructive symptoms, but should be considered whenever the relatively unusual entity of granulomatous prostatitis is diagnosed. One patient was initially treated exclusively with trimethoprim-sulfamethoxazole (TMP-SMX). He responded, but noted recurrence during the 15th month of treatment. We also report on this patient's antineutrophil cytoplasmic antibody (ANCA) titers, which correlated with clinical assessment and predicted recurrence 2 months before elevation of the Westergren sedimentation rate (WSR) and clinical diagnosis.

Topics: Autoantibodies; Cytoplasm; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Neutrophils; Prostatitis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Dapsone; Drug Therapy, Combination; Granulomatosis with Polyangiitis; Humans; Neutrophils; Sulfonamides; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Cyclophosphamide; Granulomatosis with Polyangiitis; Humans; Prospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination

It is widely believed that thoracotomy is necessary to obtain biopsy specimens adequate for the histopathologic demonstration of pulmonary Wegener's granulomatosis (WG). We report five patients with WG who were diagnosed by transbronchial biopsy (TBB). In three cases, a diagnosis of WG was made by TBB alone. In the other two patients, subsequent open lung biopsies confirmed the TBB findings but did not add essential diagnostic information. Our experience suggests TBB may be appropriate as the initial diagnostic procedure in selected cases of suspected WG. This approach requires an understanding of the diverse histologic features of WG and the correlation of clinical and pathologic data.

Topics: Adolescent; Adult; Aged; Biopsy; Cyclophosphamide; Female; Granulomatosis with Polyangiitis; Humans; Indomethacin; Lung; Male; Middle Aged; Prednisone; Trimethoprim, Sulfamethoxazole Drug Combination

Sulfamethoxazole-trimethoprim, an antimicrobial agent, was used to treat three cases of cytotoxic agent-resistant Wegener's granulomatosis; one case was refractory to a regimen consisting of azathioprine and prednisolone, and in another two cases the therapy was insufficient to control the disease. By the introduction of sulfamethoxazole-trimethoprim, which has an advantage of fewer side effects compared with the conventional agents, into the regimen, the disease condition was markedly improved in all cases within four months. Sulfamethoxazole-trimethoprim is thus considered as one of the most promising drugs to treat, especially, cytotoxic agent-resistant Wegener's granulomatosis. The possible underlying mechanism of the effect of sulfamethoxazole-trimethoprim is also described.

Topics: Adult; Anti-Infective Agents; Azathioprine; Drug Combinations; Drug Therapy, Combination; Female; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Prednisolone; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Combinations; Female; Granulomatosis with Polyangiitis; Humans; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Drug Combinations; Granulomatosis with Polyangiitis; Humans; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Considering cyclophosphamide's severe side effects there is a need for a new, less toxic treatment protocol for Wegener's granulomatosis. Here we report the first results of a prospective study using cyclophosphamide pulse therapy (monthly application) (a) as an alternative treatment in seven cases of active generalized Wegener's granulomatosis, which either showed complications under continuous cyclophosphamide treatment or in which the partial remission was not steady, and (b) as the initial treatment in five newly diagnosed patients with active generalized disease. After complete remission had been achieved in all cases in group (a), but only two cases in group (b), we started treatment with trimethoprim/sulfamethoxazole (cotrimoxazole) to maintain remission. Three of 8 patients suffered from severe relapses 9, 11 and 12 months after discontinuation of cyclophosphamide. The 3 patients in group (b) who could not be brought into remission had to be put on continuous cyclophosphamide. In addition, we treated 3 patients with newly diagnosed locoregional disease with cotrimoxazole alone. Two of these patients responded promptly and have only minor symptoms after 13 and 27 months, respectively. In one patient the disease continued to progress in the upper respiratory tract, and treatment was switched to cyclophosphamide and prednisolone after a period of 3 months. From these results we believe that cyclophosphamide pulse therapy is a successful alternative treatment protocol after partial remission has been achieved with a daily administration of cyclophosphamide or if complications, e.g-. leukopenia, arise with the continuous use of this drug. As an initial treatment, however, bolus treatment still appears to be an experimental protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anti-Infective Agents; Cyclophosphamide; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Follow-Up Studies; Granulomatosis with Polyangiitis; Humans; Prednisolone; Prospective Studies; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Aged; Anti-Infective Agents; Drug Combinations; Female; Granulomatosis with Polyangiitis; Humans; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Cyclophosphamide; Drug Combinations; Germany; Granulomatosis with Polyangiitis; History, 20th Century; Humans; Pathology; Prednisone; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Drug Combinations; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Anti-Infective Agents; Drug Combinations; Granulomatosis with Polyangiitis; Humans; Research Design; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Wegener's granulomatosis has traditionally been treated with steroids and cyclophosphamide. However, sulfamethoxazole-trimethoprim has been shown to be effective. We used it to treat a patient with this disease who had pulmonary infiltrates, sinusitis, and evidence of renal disease manifested by hematuria and red cell casts. After two months of therapy with sulfamethoxazole-trimethoprim, his hematologic and radiologic values returned to normal.

Topics: Anti-Infective Agents; Drug Administration Schedule; Drug Combinations; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Paranasal Sinus Diseases; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Cyclophosphamide has proved to be the most effective therapy for Wegener's granulomatosis, but mortality remains high at many medical centers, and the necessity for giving this toxic agent for many years to prevent relapses remains a major problem. Successful treatment of this disease with sulfamethoxazole-trimethoprim has been reported by DeRemee et al, and experience in a series of ten patients at Thomas Jefferson University Hospital, Philadelphia, confirms its effectiveness. Nine patients are in remission, and the condition of one patient improved. Relapses occurred in four patients after intervals of remission ranging from four to 30 months, but responded to increased doses of trimethoprim in two patients, while two patients required resumption of therapy with cytotoxic agents. Although the effects of sulfamethoxazole-trimethoprim are suppressive rather than curative, its use represents a major advance in treatment of Wegener's granulomatosis, permitting successful treatment of many patients without high toxic doses of cyclophosphamide and prednisone.

Topics: Adolescent; Adult; Aged; Chemical and Drug Induced Liver Injury; Drug Combinations; Female; Granulomatosis with Polyangiitis; Humans; Male; Middle Aged; Recurrence; Sulfamethoxazole; Thrombocytopenia; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Wegener granulomatosis was diagnosed in a 42-year-old woman in 1965. Although a regimen of azathioprine and prednisone was helpful, the disease progressed. Cyclophosphamide was added to this regimen in 1969. On three separate occasions her disease relapsed when cyclophosphamide therapy was discontinued. In 1984, she developed cyclophosphamide-resistant disease and drug toxicity. We were able to discontinue cyclophosphamide therapy after a trimethoprim-sulfamethoxazole regimen that was begun in February 1985 led to rapid improvement, a fall in the erythrocyte sedimentation rate, and a complete remission. Her 22-year survival is the longest one reported. Because patients with Wegener granulomatosis sometimes respond to trimethoprim-sulfamethoxazole, this therapy deserves careful study and implies that Wegener granulomatosis is an as yet unidentified infection.

Topics: Blood Sedimentation; Cyclophosphamide; Drug Combinations; Drug Therapy, Combination; Female; Granulomatosis with Polyangiitis; Hematuria; Hemoglobins; Humans; Leukocyte Count; Middle Aged; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adolescent; Drug Combinations; Female; Granulomatosis with Polyangiitis; Humans; Nose Diseases; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Twelve patients with Wegener's granulomatosis were treated with antimicrobial agents, chiefly trimethoprim-sulfamethoxazole. The clinical course improved in 11 of the 12 patients who received this treatment. The success of antimicrobial treatment suggests the possibility of a microbial infection as the inciting cause of Wegener's granulomatosis in some patients. Alternatively, these agents--in particular, trimethoprim-sulfamethoxazole--may possess immunosuppressant activity.

Topics: Adult; Aged; Cyclophosphamide; Drug Combinations; Drug Therapy, Combination; Female; Granulomatosis with Polyangiitis; Humans; Lung; Male; Middle Aged; Nose; Prednisone; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination