å¡ CASE REPORT
å¡
Wegener's Granulomatosis in a Patient with a Rheumatoid Arthritis Hiroyuki Ohashi, Mitsuyasu Itoh, Noriyoshi Ogawa, Yuichiro Sudo, Shigeki Endo, Tadamasa Okugawa, Hisako Ito*, Hiroyuki Mineta* and Michihiko Nozue* A 38-year-old woman with rheumatoid arthritis who developed Wegener's granulomatosis is described. Wegener's granulomatosis appeared with saddle nose, perforation in her nasal septum, and granuloma in the nasal cavity. Laboratory evaluation showed a positive rheumatoid factor and circulating immune complex. Radiographic examination revealed ankylotic changes in both wrist and elbow joints. Bilateral anosmia and other disease manifestations completely responded to treatment with oral cyclophosphamide and prednisolone. (Internal Medicine 31: 1128-1131, 1992) Key words: granuloma, rheumatoid factor, ankylosis, immune complex, cyclophosphamide
Introduction
lomatosis was suspected, she was referred and admitted to our department in May 1986. Wegener's granulomatosis, a relatively rare disease, Physical examination revealed anemic conjunctiva, is defined as a syndrome involving the nasopharangeal saddle nose, perforation in her nasal septum and granu and respiratory tract, as well as the kidneys. It is usually loma in the nasal cavity. No lymphadenopathy was accompanied by severe systemic complications. It is found. Contracture was found in her bilateral elbow joints. Swelling and pain were noted in her right index well known that the disease often presents symptoms and middle fingers and left knee joint. Neurological resembling rheumatoid arthritis (RA), such as poly examination revealed bilateral anosmia. arthritis and a positive rheumatoid factor in the serum Laboratory evaluation on admission revealed RBC of (1-3). However, only a few cases of Wegener's granulo 455 x lO4/cmm, hemoglobin of 10.0g/dl and WBC of matosis complicated with typical RA have been reported 7500/cmm with 20% lymphocytes, 73% neutrophils, 3% (4-8). Here we describe a patient in whom typical monocytes, 2% basophils, 1% eosinophils, and 1% aty features of RA began to appear 3 years before the pical lymphocytes. The platelet count was 43.3 X 104/cmm, onset of saddle nose, which confirmed the diagnosis and her erythrocyte sedimentation rate (Westergren of Wegener's granulomatosis. Case Report method) was 81mm/h. Electrolytes were within the normal range, and blood urea nitrogen was ll.8mg/dl A 38-year-old woman developed polyarthralgia and (normal: less than 22.0mg/dl). The serum level of cre morning stiffness in 1981, and was diagnosed as having atinine was 0.5mg/dl (normal: less than l.l mg/dl), uric RA in a nearby clinic. Her symptoms did not improve in acid, 3.5 mg/dl (normal: less than 5.1 mg/dl); cholesterol, spite of treatment with non-steroidal anti-inflammatory 169mg/dl (normal: less than 220mg/dl); fasting blood drugs and gold thiomarate which was given for 3 years glucose, 87mg/dl; LDH, 197W.U. (normal: less than starting in 1982. In 1984 she complained of nasal bleeding 340W.U.); GOT, 10 Karm. U. (normal: less than 23 and noticed that she had developed saddle nose. Two K.U.); GPT, 4Karm. U. (normal: less than 16K.U.); years later, she visited the department of otorhinol alkaline phosphatase, 6.3K.A.U. (normal: less than 10K.A.U.); amylase, 189BSIU; total protein, 6.6g/dl; aryngology in another hospital, and it was found that her Her nasal membrane bled easily. Since Wegener's granualbumin, 3.2g/dl. Serum electrophoresis revealed an nasal septum was perforated with marginated granuloma. increase of alpha-1 (0.33g/dl), alpha-2 (1.10g/dl), and From the Third Department of Internal Medicine and *the Department of Otorhinolaryngology, Hamamatsu University School of Medici gamma-globulin (1.43 g/dl). Fibrinogen (447 mg/dl) was Hamamatsu Received for publication December 26, 1991; Accepted for publication June 15, 1992 Reprint requests should be addressed to Dr. Mitsuyasu Itoh, the Third Department of Internal Medicine, Hamamatsu University School o Medicine, 3600 Handa-cho, Hamamatsu 431-31, Japan 1128
Internal
Medicine
Vol. 31, No. 9 (September
1992)
Wegener's Granulomatosis also increased. PSP test and creatinine clearance were normal. C-reactive protein was 7.3mg/dl. RA test, RAHA (X160) and Waaler-Rose (x4) were all positive. Antineutrophil cytoplasmic antibody (ANCA) was negative. Circulating immune complexes were positively indicated as 0.584 by polyethylene glycol precipitation (normal: 0.203 ± 0.132) and 12.4% by protein A binding (normal: 1.5-5.5). The phenotype of the lymphocytes in the peripheral blood was CD3, 47.2%; CD4, 30.5%; CD8, 14.6%; B1? 4.8%; Ia+ T, 3.54%; CD4+ 2H4+, 19.7%; CD4+ 4B4+, 8.4%; CD4:CD8 ratio 2.09. On radiographic examination, joint space narrowing was found in distal and proximal interphalangeal and
and RA
shown in Fig. 1. Similar ankylotic changes were observed in both elbow joints. Radioopaque change was noted in upper and frontal sinus in Waters view. A chest roent genogram was normal. Electrocardiography showed a normal pattern. A biopsy specimen was obtained from
metacarpophalangeal joints in both hands, in addition to ulnar deviation, and ankylosis in both wrist joints as
Fig. 1. Hand of a 38-year-old woman with Wegener's granulo Fig. 2. Biopsy specimen from the nasal granuloma showing arteritis matosis and rheumatoid arthritis. The joint spaces are narrow in distal and proximal interphalangeal and metacarpophalangeal joints in with both cellular infiltration (A) and a giant cell (B). (HE stain, x50). hands, and ankylosis is seen in both wrist joints.
Fig. 3. Clinical course. PSL: prednisolone, CIC: circulating immune complex, PLTS: platelets, FIBG: fibrinogen. Internal
Medicine
Vol. 31, No. 9 (September
1992)
1129
Ohashi et al the tumor in the nasal cavity. Histological examination revealed arteritis with cellular infiltration, giant cells, and epidermoid cells (Fig. 2). Treatment was strated with prednisolone (60 mg/day) , and anosmia gradually disappeared as shown in Fig. 3. Cyclophosphamide was started two weeks later. A com bination of prednisolone and cyclophosphamide achieved recovery of the olfactory function and diminished the tumor in her nasal cavity. Her arthritis was also im proved, while the Lansbury index was decreased from 63% to 20%. ESR, titers of rheumatoid factor and RAHA were all decreased. Circulating immune com plexes, platelet counts, and serum fibrinogen were also normalized. The dose of prednisolone was tapered to 10mg on alternative days. Complete remission is con tinuing to the present. Discussion The present case showed classic RA, however nasal obstruction, nasal bleeding, and saddle nose became apparent during the clinical course of RA. The long standing disease duration of RA excludes the possibility of prodromal symptoms for Wegener's granulomatosis from polyarthragia and positive rheumatoid factor. The destructive change in her wrist and elbow joints proved the coexistance of RA. Polyarthralgia is a relatively common symptom for Wegener's granulomatosis, but arthritis is transient and not destructive (1-3). Recent studies confirmed this observation and drew the same conclusion that erosive arthritis is rare in Wegener's granulomatosis (9-13). An exceptional case who pre sented erosive arthritis in Wegener's granuolomatosis was reported (14). That case showed marginal erosion in metacarpophalangeal joints and negative rheumatoid factor. The present patient differed from that case, since she had the typical articular symptoms, destructive The duration between the two disease are, in fact, longer changes proven in X-ray findings, and positive rheu than the previous reports (4, 5). Moreover, the histology matoid factors. The patient is quite an unusual case. of her nasal granuloma was typical of that found in Wegener's granulomatosis. Although ANCA was nega tive in this patient, it has been reported that only a small portion of cases are positive in the early stages of the disease (15, 16). The lungs and kidneys were not involved in the present case. It is suggested that this case might be a so-called "limited Wegener's granulomatosis" (5, 17) or UE" form in the ELK classification (18). Six cases have been reported in the English literature thus far, although only four case reports provided detailed in formation regarding the clinical picture to confirm the complication of RA (4, 7, 8). Among the six cases, four cases were considered to be a limited formisofstill Wegener's The etiology of Wegener's granulomatosis granulomatosis. 1130
unknown, although an allergy to unknown factors has been suggested (1, 16, 19). The high prevalence of cir culating immune complexes has been reportd (18), and that is the case in this patient. It is also well known that RA shows a high incidence of circulating immune com plex. Furthermore, both Wegener's granulomatosis and RA show a high incidence of rheumatoid factors. It is possible that a common etiological factor implicated the production of an immune complex in this patient, although the component of such an immune complex has not been elucidated. However, a recent study has claimed that pathogenic significance of abnormal cell mediated immune responses and possible involvement of cytokines were more important than the circulating immune complexes because of the lack of immune com plex deposits and the predominant infiltration of T cells and monocytes in the biopsied specimen in the lung (16).prognosis Further studies are necessary to elucidate The of Wegener's granulomatosis hasthe dra pathogenesis of both diseases. matically improved after the introduction of cytotoxic drugs, such as cyclophosphamide, into the therapeutic regimen (20, 21). Complete remission was obtained in this case with a combination of prednisolone and cyclo phosphamide. The justification of this combined therapy awaits further clinical studies. References 1) Fauci AS, Wolff SM. Wegener's granulomatosis: Studies in eighteen patients and a review of the literature. Medicine 52: 535, 1973. 2) Israel HL, Patchefsky AS, Saldana MJ. Wegener's granulo matosis, lymphomatoid granulomatosis, and benign lymphocytic angitis and granulomatosis of lung. Ann Intern Med 87: 691, 1977. 3) Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener's granulo matosis: Prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 98: 76, 1983. 4) Pritchard MH, Gow PJ. Wegener's granulomatosis presenting as rheumatoid arthritis (two cases). Proc R Soc Med 69: 501, 1976. 5) Carrington CB, Liebow AA. Limited forms of angitis and granu lomatosis of Wegener's type. Am J Med 41: 497, 1996. 6) Bywaters EGL, Scott JT. Wegener's granulomatosis. in: Progress in Clinical Rheumatology, Dixon ASTJ, Ed. Little, Brown, Boston, 1965, p. 150. 7) Sturrock RD, Ratnesar P. Wegener's granulomatosis occurring in a patient with pre-existing rheumatoid arthritis. Br J Clin Pract 28: 183, 1974. 8) Sevel D. Necrogranulomatous keratitis. Associated with Wegener's granulomatosis and rheumatoid arthritis. Am J Ophthalmol 63: 250, 1967. 9) Littlejohn GO, Ryan PJ, Holdsworth SR. Wegener's granulo matosis: Clinical features and outcome in seventeen patients. Aust NZJ Med 15: 241, 1985. 10) Noritake DT, Weiner SR, Bassett LW, Paulus HE, Weisbart R. Rheumatic manifestations of Wegener's granulomatosis. J Rheumatol 14: 949, 1987. ll) Boudes P. Purely granulomatous Wegener's granulomatosis: A new concept for an old disease. Semin Arthritis Rheum 19: Internal
Medicine
Vol. 31, No. 9 (September
1992)
Wegener's Granulomatosis 365,
1990.
Cordier J-F, Valeyre D, Guillevin L, Loire R, Brechot J-M. Pulmonary Wegener's granulomatosis: A clinical and imaging study of 77 cases. Chest 97: 906, 1990. Alcalay M, Azais I, Pallier B et al. Les manifestations articulaires de la maladie de Wegener. Rev Rheum 57: 845, 1990 (in French). Jacobs RP, Moore M, Brower A. Wegener's granulomatosis presenting with erosive arthritis. Arthritis Rheum 30: 943, 1987. Wegener F. Wegener's granulomatosis: Thoughts and observations of a pathologist. Eur Arch Otorhinolaryngol 247: 133, 1990.
Gross WL. Wegerer's granulomatosis: Newaspects of the disease course, immunodiagnostic procedures, and stage-adapted treat-
Internal
Medicine
Vol. 31, No. 9 (September
1992)
and RA
ment. Sarcoidosis 6: 15, 1989. Cassan SM, Coles DT, Harrison EG Jr. The concept of limited forms of Wegener's granulomatosis. Am J Med 49: 366, 1970. DeRemee RA, McDonald TJ, Harrison EG, Coles DT. Wegener's granulomatosis. Anatomic correlate, a proposed classification. Mayo Clin Proc 51: 777, 1976. Howell SB, Epstein WV. Circulating immunoglobulin complexes in Wegener's granulomaosis. Am J Med 60: 259, 1976. Novack SN, Pearson CM. Cyclophosphamide therapy in Wegener's granulomatosis. N Engl J Med 284: 938, 1971. Hoffman GS, Leavitt RY, Fleisher TA, Minor JR, Fauci AS. Treatment of Wegener's granulomatosis with intermittent high dose intravenous cyclophosphamide. Am J Med 89: 403, 1990.
1131
å¡
Wegener's Granulomatosis in a Patient with a Rheumatoid Arthritis Hiroyuki Ohashi, Mitsuyasu Itoh, Noriyoshi Ogawa, Yuichiro Sudo, Shigeki Endo, Tadamasa Okugawa, Hisako Ito*, Hiroyuki Mineta* and Michihiko Nozue* A 38-year-old woman with rheumatoid arthritis who developed Wegener's granulomatosis is described. Wegener's granulomatosis appeared with saddle nose, perforation in her nasal septum, and granuloma in the nasal cavity. Laboratory evaluation showed a positive rheumatoid factor and circulating immune complex. Radiographic examination revealed ankylotic changes in both wrist and elbow joints. Bilateral anosmia and other disease manifestations completely responded to treatment with oral cyclophosphamide and prednisolone. (Internal Medicine 31: 1128-1131, 1992) Key words: granuloma, rheumatoid factor, ankylosis, immune complex, cyclophosphamide
Introduction
lomatosis was suspected, she was referred and admitted to our department in May 1986. Wegener's granulomatosis, a relatively rare disease, Physical examination revealed anemic conjunctiva, is defined as a syndrome involving the nasopharangeal saddle nose, perforation in her nasal septum and granu and respiratory tract, as well as the kidneys. It is usually loma in the nasal cavity. No lymphadenopathy was accompanied by severe systemic complications. It is found. Contracture was found in her bilateral elbow joints. Swelling and pain were noted in her right index well known that the disease often presents symptoms and middle fingers and left knee joint. Neurological resembling rheumatoid arthritis (RA), such as poly examination revealed bilateral anosmia. arthritis and a positive rheumatoid factor in the serum Laboratory evaluation on admission revealed RBC of (1-3). However, only a few cases of Wegener's granulo 455 x lO4/cmm, hemoglobin of 10.0g/dl and WBC of matosis complicated with typical RA have been reported 7500/cmm with 20% lymphocytes, 73% neutrophils, 3% (4-8). Here we describe a patient in whom typical monocytes, 2% basophils, 1% eosinophils, and 1% aty features of RA began to appear 3 years before the pical lymphocytes. The platelet count was 43.3 X 104/cmm, onset of saddle nose, which confirmed the diagnosis and her erythrocyte sedimentation rate (Westergren of Wegener's granulomatosis. Case Report method) was 81mm/h. Electrolytes were within the normal range, and blood urea nitrogen was ll.8mg/dl A 38-year-old woman developed polyarthralgia and (normal: less than 22.0mg/dl). The serum level of cre morning stiffness in 1981, and was diagnosed as having atinine was 0.5mg/dl (normal: less than l.l mg/dl), uric RA in a nearby clinic. Her symptoms did not improve in acid, 3.5 mg/dl (normal: less than 5.1 mg/dl); cholesterol, spite of treatment with non-steroidal anti-inflammatory 169mg/dl (normal: less than 220mg/dl); fasting blood drugs and gold thiomarate which was given for 3 years glucose, 87mg/dl; LDH, 197W.U. (normal: less than starting in 1982. In 1984 she complained of nasal bleeding 340W.U.); GOT, 10 Karm. U. (normal: less than 23 and noticed that she had developed saddle nose. Two K.U.); GPT, 4Karm. U. (normal: less than 16K.U.); years later, she visited the department of otorhinol alkaline phosphatase, 6.3K.A.U. (normal: less than 10K.A.U.); amylase, 189BSIU; total protein, 6.6g/dl; aryngology in another hospital, and it was found that her Her nasal membrane bled easily. Since Wegener's granualbumin, 3.2g/dl. Serum electrophoresis revealed an nasal septum was perforated with marginated granuloma. increase of alpha-1 (0.33g/dl), alpha-2 (1.10g/dl), and From the Third Department of Internal Medicine and *the Department of Otorhinolaryngology, Hamamatsu University School of Medici gamma-globulin (1.43 g/dl). Fibrinogen (447 mg/dl) was Hamamatsu Received for publication December 26, 1991; Accepted for publication June 15, 1992 Reprint requests should be addressed to Dr. Mitsuyasu Itoh, the Third Department of Internal Medicine, Hamamatsu University School o Medicine, 3600 Handa-cho, Hamamatsu 431-31, Japan 1128
Internal
Medicine
Vol. 31, No. 9 (September
1992)
Wegener's Granulomatosis also increased. PSP test and creatinine clearance were normal. C-reactive protein was 7.3mg/dl. RA test, RAHA (X160) and Waaler-Rose (x4) were all positive. Antineutrophil cytoplasmic antibody (ANCA) was negative. Circulating immune complexes were positively indicated as 0.584 by polyethylene glycol precipitation (normal: 0.203 ± 0.132) and 12.4% by protein A binding (normal: 1.5-5.5). The phenotype of the lymphocytes in the peripheral blood was CD3, 47.2%; CD4, 30.5%; CD8, 14.6%; B1? 4.8%; Ia+ T, 3.54%; CD4+ 2H4+, 19.7%; CD4+ 4B4+, 8.4%; CD4:CD8 ratio 2.09. On radiographic examination, joint space narrowing was found in distal and proximal interphalangeal and
and RA
shown in Fig. 1. Similar ankylotic changes were observed in both elbow joints. Radioopaque change was noted in upper and frontal sinus in Waters view. A chest roent genogram was normal. Electrocardiography showed a normal pattern. A biopsy specimen was obtained from
metacarpophalangeal joints in both hands, in addition to ulnar deviation, and ankylosis in both wrist joints as
Fig. 1. Hand of a 38-year-old woman with Wegener's granulo Fig. 2. Biopsy specimen from the nasal granuloma showing arteritis matosis and rheumatoid arthritis. The joint spaces are narrow in distal and proximal interphalangeal and metacarpophalangeal joints in with both cellular infiltration (A) and a giant cell (B). (HE stain, x50). hands, and ankylosis is seen in both wrist joints.
Fig. 3. Clinical course. PSL: prednisolone, CIC: circulating immune complex, PLTS: platelets, FIBG: fibrinogen. Internal
Medicine
Vol. 31, No. 9 (September
1992)
1129
Ohashi et al the tumor in the nasal cavity. Histological examination revealed arteritis with cellular infiltration, giant cells, and epidermoid cells (Fig. 2). Treatment was strated with prednisolone (60 mg/day) , and anosmia gradually disappeared as shown in Fig. 3. Cyclophosphamide was started two weeks later. A com bination of prednisolone and cyclophosphamide achieved recovery of the olfactory function and diminished the tumor in her nasal cavity. Her arthritis was also im proved, while the Lansbury index was decreased from 63% to 20%. ESR, titers of rheumatoid factor and RAHA were all decreased. Circulating immune com plexes, platelet counts, and serum fibrinogen were also normalized. The dose of prednisolone was tapered to 10mg on alternative days. Complete remission is con tinuing to the present. Discussion The present case showed classic RA, however nasal obstruction, nasal bleeding, and saddle nose became apparent during the clinical course of RA. The long standing disease duration of RA excludes the possibility of prodromal symptoms for Wegener's granulomatosis from polyarthragia and positive rheumatoid factor. The destructive change in her wrist and elbow joints proved the coexistance of RA. Polyarthralgia is a relatively common symptom for Wegener's granulomatosis, but arthritis is transient and not destructive (1-3). Recent studies confirmed this observation and drew the same conclusion that erosive arthritis is rare in Wegener's granulomatosis (9-13). An exceptional case who pre sented erosive arthritis in Wegener's granuolomatosis was reported (14). That case showed marginal erosion in metacarpophalangeal joints and negative rheumatoid factor. The present patient differed from that case, since she had the typical articular symptoms, destructive The duration between the two disease are, in fact, longer changes proven in X-ray findings, and positive rheu than the previous reports (4, 5). Moreover, the histology matoid factors. The patient is quite an unusual case. of her nasal granuloma was typical of that found in Wegener's granulomatosis. Although ANCA was nega tive in this patient, it has been reported that only a small portion of cases are positive in the early stages of the disease (15, 16). The lungs and kidneys were not involved in the present case. It is suggested that this case might be a so-called "limited Wegener's granulomatosis" (5, 17) or UE" form in the ELK classification (18). Six cases have been reported in the English literature thus far, although only four case reports provided detailed in formation regarding the clinical picture to confirm the complication of RA (4, 7, 8). Among the six cases, four cases were considered to be a limited formisofstill Wegener's The etiology of Wegener's granulomatosis granulomatosis. 1130
unknown, although an allergy to unknown factors has been suggested (1, 16, 19). The high prevalence of cir culating immune complexes has been reportd (18), and that is the case in this patient. It is also well known that RA shows a high incidence of circulating immune com plex. Furthermore, both Wegener's granulomatosis and RA show a high incidence of rheumatoid factors. It is possible that a common etiological factor implicated the production of an immune complex in this patient, although the component of such an immune complex has not been elucidated. However, a recent study has claimed that pathogenic significance of abnormal cell mediated immune responses and possible involvement of cytokines were more important than the circulating immune complexes because of the lack of immune com plex deposits and the predominant infiltration of T cells and monocytes in the biopsied specimen in the lung (16).prognosis Further studies are necessary to elucidate The of Wegener's granulomatosis hasthe dra pathogenesis of both diseases. matically improved after the introduction of cytotoxic drugs, such as cyclophosphamide, into the therapeutic regimen (20, 21). Complete remission was obtained in this case with a combination of prednisolone and cyclo phosphamide. The justification of this combined therapy awaits further clinical studies. References 1) Fauci AS, Wolff SM. Wegener's granulomatosis: Studies in eighteen patients and a review of the literature. Medicine 52: 535, 1973. 2) Israel HL, Patchefsky AS, Saldana MJ. Wegener's granulo matosis, lymphomatoid granulomatosis, and benign lymphocytic angitis and granulomatosis of lung. Ann Intern Med 87: 691, 1977. 3) Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener's granulo matosis: Prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 98: 76, 1983. 4) Pritchard MH, Gow PJ. Wegener's granulomatosis presenting as rheumatoid arthritis (two cases). Proc R Soc Med 69: 501, 1976. 5) Carrington CB, Liebow AA. Limited forms of angitis and granu lomatosis of Wegener's type. Am J Med 41: 497, 1996. 6) Bywaters EGL, Scott JT. Wegener's granulomatosis. in: Progress in Clinical Rheumatology, Dixon ASTJ, Ed. Little, Brown, Boston, 1965, p. 150. 7) Sturrock RD, Ratnesar P. Wegener's granulomatosis occurring in a patient with pre-existing rheumatoid arthritis. Br J Clin Pract 28: 183, 1974. 8) Sevel D. Necrogranulomatous keratitis. Associated with Wegener's granulomatosis and rheumatoid arthritis. Am J Ophthalmol 63: 250, 1967. 9) Littlejohn GO, Ryan PJ, Holdsworth SR. Wegener's granulo matosis: Clinical features and outcome in seventeen patients. Aust NZJ Med 15: 241, 1985. 10) Noritake DT, Weiner SR, Bassett LW, Paulus HE, Weisbart R. Rheumatic manifestations of Wegener's granulomatosis. J Rheumatol 14: 949, 1987. ll) Boudes P. Purely granulomatous Wegener's granulomatosis: A new concept for an old disease. Semin Arthritis Rheum 19: Internal
Medicine
Vol. 31, No. 9 (September
1992)
Wegener's Granulomatosis 365,
1990.
Cordier J-F, Valeyre D, Guillevin L, Loire R, Brechot J-M. Pulmonary Wegener's granulomatosis: A clinical and imaging study of 77 cases. Chest 97: 906, 1990. Alcalay M, Azais I, Pallier B et al. Les manifestations articulaires de la maladie de Wegener. Rev Rheum 57: 845, 1990 (in French). Jacobs RP, Moore M, Brower A. Wegener's granulomatosis presenting with erosive arthritis. Arthritis Rheum 30: 943, 1987. Wegener F. Wegener's granulomatosis: Thoughts and observations of a pathologist. Eur Arch Otorhinolaryngol 247: 133, 1990.
Gross WL. Wegerer's granulomatosis: Newaspects of the disease course, immunodiagnostic procedures, and stage-adapted treat-
Internal
Medicine
Vol. 31, No. 9 (September
1992)
and RA
ment. Sarcoidosis 6: 15, 1989. Cassan SM, Coles DT, Harrison EG Jr. The concept of limited forms of Wegener's granulomatosis. Am J Med 49: 366, 1970. DeRemee RA, McDonald TJ, Harrison EG, Coles DT. Wegener's granulomatosis. Anatomic correlate, a proposed classification. Mayo Clin Proc 51: 777, 1976. Howell SB, Epstein WV. Circulating immunoglobulin complexes in Wegener's granulomaosis. Am J Med 60: 259, 1976. Novack SN, Pearson CM. Cyclophosphamide therapy in Wegener's granulomatosis. N Engl J Med 284: 938, 1971. Hoffman GS, Leavitt RY, Fleisher TA, Minor JR, Fauci AS. Treatment of Wegener's granulomatosis with intermittent high dose intravenous cyclophosphamide. Am J Med 89: 403, 1990.
1131
