Acta Oto-Laryngologica
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Wegener's Granulomatosis, Immunosuppressive Therapy H. Thorkelsen & P. Berdal To cite this article: H. Thorkelsen & P. Berdal (1976) Wegener's Granulomatosis, Immunosuppressive Therapy, Acta Oto-Laryngologica, 82:1-6, 208-211, DOI: 10.3109/00016487609120885 To link to this article: http://dx.doi.org/10.3109/00016487609120885
Published online: 08 Jul 2009.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20 Download by: [Universität Osnabrueck]
Date: 17 March 2016, At: 00:40
Acta Otolaryngol82: 208-21 1, 1976
W E G E N E R S GRANULOMATOSIS, IMMUNOSUPPRESSIVE THERAPY
H. Thorkelsen and P. Berdal From the ENT Department, Rikshospitalet, Oslo, Norway
Downloaded by [Universität Osnabrueck] at 00:40 17 March 2016
Abstracr. We present a study of 11 patients with We-
gener’s granulomatosis. Seven of these were treated with Azathioprine (Imurel) combined with prednisone. Of these, 4 patients rapidly improved after the treatment was started. Atelectatic changes in the lungs disappeared. A rapidly progressive renal failure was reversed, and renal function returned to normal. Large lesions of the skin also improved. The treatment has now lasted 24-43 years without interruption. We have not had any serious side effects due to Imurel. We believe that the good effect of the treatment is due to immunosuppression by the drugs.
Wegener’s granulomatosis is a rare disease of unknown aetiology. Histologically, it is characterized by generalized focal necrotizing vasculitis with perivascular infiltration of lymphocytes. At the present time, it is regarded as an auto-immune disease with an unknown antigen. Untreated, the patients die within 6 months (Shillitoe et al., 1974; Asin et al., 1972). Usually, the upper respiratory tract is first involved; later the disease is also found in the lower respiratory tract including the lung parenchyma and in the kidneys. Other organs may also be involved, e.g. the orbita, middle ear, skin and joints. Confronted with a disease affecting the upper respiratory tract, lungs and kidneys, the diagnosis of Wegener’s granulomatosis should be considered (Gonzales & Ordstrand, 1973). A chronic otitis which does not improve during treatment may be a manifestation of Wegener’s granulomatosis (Linthicum & Schwartzman, 1972). TREATMENT The principles of treatment in Wegener’s granulomatosis have varied according to the current view of the nature of the disease. 1 . Before 1955, the treatment was purely Acta Otolaryngol82
symptomatic, and the patients usually died within 6 months after the onset of the disease. 2. From about 1955 until the latter part of 1960, the treatment consisted of X-rays and steroids, and this led to great optimism. No doubt, this treatment has improved the prognosis, but only to a slight extent. The results of the treatment were mostly due to a general antiinflammatory effect. 3. From the end of 1960, cytostatics have been used (Moeschlin, 1969; Skevas & Schmidt-Baumler, 1974; Teisberg & Enger, 1970; Harst, 1973). Very good results have been reported, and many patients have been able to start working again. Imurel (azathioprine) is a cytostatic drug (antimetabolite) with an immunosuppressive effect and few side effects. Therapeutically, regression of the infiltrates and an improvement of the patient’s general health may be achieved. Examples of the favourable results of Imure1 treatment appear from the following case reports:
Case no. 5 (Table 11) A 38-year-old male factory worker, admitted to Rikshospitalet in May 1972. His complaints were pain in the nose, nasal stuffiness and frequent nose bleedings since November 1971. H e had been unsuccessfully treated with antibiotics for rhinosinusitis by his family doctor. On admission, an ulcerating infiltration in the upper dorsal part on both sides of the nose was found. A biopsy specimen from the nasal mucosa showed ulceration and marked subacute inflammation with eosinophilia and giant
Wegener’s granulomatosis
209
Table I. Wegener’s granulomatosis. Treatment with X-ray and/or corticosteroids ~~
ProCase fession
Sympt. duration (months)
Treatment and duration of treatment
no.
Sex
Age
8 SS
Clerk
55
Oral and nasal mucosa, lungs
46
Prednisone 20 mg/day 3 months prior to death
9
Plumber
63
Ramus mandibulae, epipharynx, lungs
28
X-ray: Jan. 1963, 1 150 R mandibular field Feb. 1963, 1000 R mandibular field Oct. 1%3. 450 R mandibular field
Right tonsil
35
W Downloaded by [Universität Osnabrueck] at 00:40 17 March 2016
Localisation of disease
M
M
10
Salesman 52
E
M
I1
Teacher M
RU
52
Mucosaofnose and maxillary sinus
9
X-ray: Dec. 1972, 5 800 R Prednisone 60 mg/day reduced to 2.5 mg/day from Dec. 1972. X-ray: Dec. 1%0. 1800 R nasal field May 1961,’ 1 800 R nasal field Prednisone 40 mg/day Dec. 1960-May 1961
cells, interpreted as Wegener’s granulomatosis. X-ray showed atelectasis of the posterior basal segment in the left lung. Bronchoscopy: Papillomatous tumour occluding the lumen immediately peripheral to the opening of the apical bronchus of the left lower lung. Later he got haematuria, proteinuria, isosthenuria. Serum creatinine increased to 6.1 mg/dl. Creatinine-clearance fell to 29 ml/min. Biopsy of the kidneys showed proliferative and interstitial inflammatory changes and fibrinoid necrosis. Haemoptysis occurred. Rapidly deteriorating kidney failure followed. Serum electrophoresis showed increased alpha, and alpha, globulin and slightly increased immunoglobulin G and A. In June 1972, treatment started with Imurel 50 mg X 5, and prednisone 5 mg X 2, daily. Gradual improvement was obtained, and 5 months later the serum creatinine was 1.6 mg/dl. The creatinine clearance increased to 140 ml/min. A repeated biopsy from the kidney showed sclerosis of the glomeruli and great changes as compared to the first biopsy. Repeated X-ray showed almost normal lungs. Having been disabled for 14 years, he now returned to work and has later been fully employed. The lung function
Survival time following treatment
Effect Progression of disease Dead of bronchopneumonia
3 months Dead
16 months Progression of Dead disease Dead of lung abscess (May 1964) Great improvement. Full-time employed
30 months Alive
No improvement
8 months Dead
No improvement Dead 1.7.61
is normal. The administration of 10 mg prednisone and 225 mg Imurel daily has been continued. Case no. 7 (Table 11) A 41-year-old female nurse was admitted to Rikshospitalet in October 1972. Her complaints were: Since August 1972 pain in the left cheek radiating to the nose and nasal stuffiness on the left side. On admission, a swelling on the left cheek was found and the left eye was dislocated laterally. X-rays showed an infiltration in the left lung and exudate in the pleura. Later she had a bloodtinged nasal secretion. She presented a tumour-like infiltration in the nose. A biopsy specimen showed changes consistent with Wegener’s granulomatosis. She also had haematuria. The serum creatinine was 2.1 mg/ dl. She was ill and confined to bed. In November 1972, Imurel in a daily dose of 50 mg X 3 and prednisone, 10 mg x 3 , were administered. The general status rapidly improved and the X-ray changes in the lungs gradually decreased. SR decreased from 115 mm to 23 mm in the course of a few months. After 6 months, in the spring of 1973, she was again fully emAcIa OtoIaryngol82
210
H . Thorkelsen and P . Berdal
Downloaded by [Universität Osnabrueck] at 00:40 17 March 2016
Table 11. Wegener’s granulomatosis. Treatment with cytostatics Case no.
Profession Sex
1 LH
Glazier M
59
2 LJ
Upholsterer M
63
Age
3 TN
Typist F
28
4 A0
Shop girl F
65
5 LL
Factory worker 38
6 IJH
Housewife F
55
7 EHT
Nurse F
41
M
~~~~~~~~
Localisation of disease
SYmPt. duration (months)
Oral mucosa, skin of penis and face, lungs
96
Orbital tissue, kidneys,lungs
34
A. X-ray
B. Imurel 150 mg/day Prednisone 15 mg/day A. Prednisone 40 mg/day Imurel 150 mg/day B. Prednisone 80 mg/day Natulan 200 mglday Cyclophosphamid 1 000 mg i.v. weekly Vinblastin 10 mg i.v. weekly C. Cyclophosphamid 50 mg/ day oral. Prednisone 15 mg/day D. No cytostatics
Duration of treatment A. 1966,67,70,71 B. Last 3 months before death A. 6 months B. 3 sequenceseach of 2 weeks, interval 1 month
C. 2months
D. Last year of life 34 months continuous
Nasal and palatal mucosa. Skin of leg, tonsils Maxillary sinus, orbital tissues
36
Imurel200 mg/day Prednisone 60-10 mg/day
54
Imurel200 mg/day Prednisone 10 mglday
48 months
Nasal mucosa, lungs, joints, kidneys Lungs, kidneys
42
Imurel250 mg/day Prednisone 10 mglday
36 months continuous
4
Imurel75 mg/day Prednisone 80 mg/day
4 days prior to death of renal
Nasal mucosa and bone, lungs, kidneys
36
Imurel 150-300 mglday Prednisone 10-50 mglday
32 months continuous
failure
~
ployed. The local immune response, as studied by immunhistochemical methods, was not different from that of an unspecific chronic inflammation. The B and T lymphocytes studied by marker technique and in vitro function test were normal. The phagocytosis of the granulocytes was normal. The former patient is still fully employed (January 1976). During the past 1.5 years 11 patients with Wegener’s granulomatosis have been admitted to Rikshospitalet, the Ullevaal Hospital, and to the Nordland Sentralsykehus, B o b . Among these, 7 patients have been treated with Imurel and prednisone. The 4 other patients (Table I) were given X-rays and/or prednisone treatment. Before the diagnosis, all patients had antibiotic treatment because an infectious inflammation was suspected. The X-ray treatment had delayed the proActa Otolaryngol82
Treatment
gression of the disease. It has also reduced the pain, and the general health has improved. All in all, the palliative effect has been satisfactory. Imurel combined with prednisone has been administrated to 7 patients (Table 11). In 4 of the cases, this treatment had a very good effect, although the patients probably have not been cured. Two of these patients have already been discussed (patients 5 and 7). Imurel, 200-300 mg daily, has been given, and these patients have now been treated for 244; years. The treatment is continued. Side effects necessitating discontinuation of the treatment has occurred only once in a case in which Imurel treatment was stopped for 2 weeks due to leucopenia (2 OOO/mP). The treatment has later been continued for 8 months. Side effects of prednisone, like osteoporosis or moon face, have occasionally occurred. In
Wegener’s granulomatosis
Effect
Survival time following treatment
Good first years progression of disease
81 months Dead
No improvement
26 months Dead
No improvement
21 1
patients with advanced disease, but not hopeless so, a good palliative effect has been obtained. The manifestations in the kidneys, lungs and respiratory tract have improved. The side effects (leucopenia, osteoporosis) have been few and has not necessitated delay of the treatment except for a very short period. The treatment should be continued permanently.
Downloaded by [Universität Osnabrueck] at 00:40 17 March 2016
ZUSAMMENFASSUNG No improvement Progression of disease Improvement
33 months Alive
Great improvement. Full time employed
48 months Alive
Great improvement. Full time employed
36 months Alive
No improvement
8 days Dead
Great improvement. Full time emp1oy ed
31 months Alive
3 cases, there was no definite improvement after treatment with Imurel and prednisone. One reason for the lack of effect probably was that the disease had reached an advanced stage when the treatment was commenced. Wegener’s granulomatosis, like other diseases, may have different rates of progression and, consequently, show varying clinical manifestations in different patients. This may be one of the reasons why the results of the treatment vary. Another possibility is that there may be different types of the disease with special localisations and different rates of progression (lethal granuloma of the midline, Steward’s granuloma, malignant granuloma). The treatment of Wegener’s granulomatosis with Imurel and prednisone is based partly on theoretical and hypothetical pathogenetic considerations and partly on experience. In some
Es werden elf Patienten mit Wegeners Granulomatose erwahnt, von denen sieben mit Azathioprine (Imurel) kombiniert mit Prednison behandelt wurden. Vier dieser Patienten zeigten eine schnelle Verbesserung gleich nach Beginn der Behandlung. Atelektatische Lungenveranderungen verschwanden. Ein fortschreitendes Nierenversagen horte auf und die Nierenfunktion normalisierte sich. GroBere Hautschaden heilten aus. Die Behandlung hat inzwischen 24-44 Jahre gedauert und wurde nicht abgebrochen. Wir haben keine ernste Nebenwirkungen von Imurel gesehen. Man nimmt an, daB der gute Behandlungserfolg auf einer medikamentell hervorgerufenen immunosuppressiven Wirkung beruht.
REFERENCES Asin, H . R. G., Wagenaar, J. P. M. & Swierenga, J. 1972. The mitigated form of Wegener’s disease. Scand J Respir Dis 53, 367. Domarus, H. v. 1973. Wegenersche Granulomatose als Ursache fur Kiefer-Gesichts-Schmertzen. Z Laryngol Rhinol Otol52, 901. Gonzales, L. & Ordstrand, H. S. 1973. Wegener’s granulomatosis. Radiology 107, 295. Harrison, D. F. N. 1974. Non-healing granulomata of the upper respiratory tract. Br Med J ZV, 205. Host, H . 1973. Cytostatika og cytostatisk terapi. Tidsskr Nor Laegeforen 93, 1857. Jsrgensen, K. E. 1970. Immunosuppressiv behandling af Wegener’s granulomatose. Ugeskr Laeger 132, 1549. Linthicum, F. H. & Schwartzman, J. A. 1972. Wegener’s granulomatosis appearing initially as otitis media. Trans Am Acad Ophthalmol Otolaryngol72, 301. Moeschlin, S . 1969. Grenzen und Moglichkeiten der immunosuppressiven Therapie. Therapiwoche 19, 1 . Rmdam, P. & Hansen, L. A. 1971. Wegener’s granulomatosis. Dan Med Bull 18, 43. Shillitoe, E. J., Lehner, T., Lessof, M. H. & Harrison, D. F. N. 1974. Immunological features of Wegener’s granulomatosis. Lancet I , 281. Skevas, A. & Schmidt-Baumler. U. 1974. Die Behandlung der Wegenerschen Granulomatose mit Immunosuppressiva und Kortikosteroiden. Laryngol Rhinol 0101 (Stuttg) 53, 674. Teisberg, P. & Enger, E. 1970. Immunosuppressive therapy in Wegener’s granulomatosis. Acta Med Scand 187, 7 . Wegener’s granulomatosis. 1972. Lancet 11, 519. Acta Otolaryngol82
ISSN: 0001-6489 (Print) 1651-2251 (Online) Journal homepage: http://www.tandfonline.com/loi/ioto20
Wegener's Granulomatosis, Immunosuppressive Therapy H. Thorkelsen & P. Berdal To cite this article: H. Thorkelsen & P. Berdal (1976) Wegener's Granulomatosis, Immunosuppressive Therapy, Acta Oto-Laryngologica, 82:1-6, 208-211, DOI: 10.3109/00016487609120885 To link to this article: http://dx.doi.org/10.3109/00016487609120885
Published online: 08 Jul 2009.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ioto20 Download by: [Universität Osnabrueck]
Date: 17 March 2016, At: 00:40
Acta Otolaryngol82: 208-21 1, 1976
W E G E N E R S GRANULOMATOSIS, IMMUNOSUPPRESSIVE THERAPY
H. Thorkelsen and P. Berdal From the ENT Department, Rikshospitalet, Oslo, Norway
Downloaded by [Universität Osnabrueck] at 00:40 17 March 2016
Abstracr. We present a study of 11 patients with We-
gener’s granulomatosis. Seven of these were treated with Azathioprine (Imurel) combined with prednisone. Of these, 4 patients rapidly improved after the treatment was started. Atelectatic changes in the lungs disappeared. A rapidly progressive renal failure was reversed, and renal function returned to normal. Large lesions of the skin also improved. The treatment has now lasted 24-43 years without interruption. We have not had any serious side effects due to Imurel. We believe that the good effect of the treatment is due to immunosuppression by the drugs.
Wegener’s granulomatosis is a rare disease of unknown aetiology. Histologically, it is characterized by generalized focal necrotizing vasculitis with perivascular infiltration of lymphocytes. At the present time, it is regarded as an auto-immune disease with an unknown antigen. Untreated, the patients die within 6 months (Shillitoe et al., 1974; Asin et al., 1972). Usually, the upper respiratory tract is first involved; later the disease is also found in the lower respiratory tract including the lung parenchyma and in the kidneys. Other organs may also be involved, e.g. the orbita, middle ear, skin and joints. Confronted with a disease affecting the upper respiratory tract, lungs and kidneys, the diagnosis of Wegener’s granulomatosis should be considered (Gonzales & Ordstrand, 1973). A chronic otitis which does not improve during treatment may be a manifestation of Wegener’s granulomatosis (Linthicum & Schwartzman, 1972). TREATMENT The principles of treatment in Wegener’s granulomatosis have varied according to the current view of the nature of the disease. 1 . Before 1955, the treatment was purely Acta Otolaryngol82
symptomatic, and the patients usually died within 6 months after the onset of the disease. 2. From about 1955 until the latter part of 1960, the treatment consisted of X-rays and steroids, and this led to great optimism. No doubt, this treatment has improved the prognosis, but only to a slight extent. The results of the treatment were mostly due to a general antiinflammatory effect. 3. From the end of 1960, cytostatics have been used (Moeschlin, 1969; Skevas & Schmidt-Baumler, 1974; Teisberg & Enger, 1970; Harst, 1973). Very good results have been reported, and many patients have been able to start working again. Imurel (azathioprine) is a cytostatic drug (antimetabolite) with an immunosuppressive effect and few side effects. Therapeutically, regression of the infiltrates and an improvement of the patient’s general health may be achieved. Examples of the favourable results of Imure1 treatment appear from the following case reports:
Case no. 5 (Table 11) A 38-year-old male factory worker, admitted to Rikshospitalet in May 1972. His complaints were pain in the nose, nasal stuffiness and frequent nose bleedings since November 1971. H e had been unsuccessfully treated with antibiotics for rhinosinusitis by his family doctor. On admission, an ulcerating infiltration in the upper dorsal part on both sides of the nose was found. A biopsy specimen from the nasal mucosa showed ulceration and marked subacute inflammation with eosinophilia and giant
Wegener’s granulomatosis
209
Table I. Wegener’s granulomatosis. Treatment with X-ray and/or corticosteroids ~~
ProCase fession
Sympt. duration (months)
Treatment and duration of treatment
no.
Sex
Age
8 SS
Clerk
55
Oral and nasal mucosa, lungs
46
Prednisone 20 mg/day 3 months prior to death
9
Plumber
63
Ramus mandibulae, epipharynx, lungs
28
X-ray: Jan. 1963, 1 150 R mandibular field Feb. 1963, 1000 R mandibular field Oct. 1%3. 450 R mandibular field
Right tonsil
35
W Downloaded by [Universität Osnabrueck] at 00:40 17 March 2016
Localisation of disease
M
M
10
Salesman 52
E
M
I1
Teacher M
RU
52
Mucosaofnose and maxillary sinus
9
X-ray: Dec. 1972, 5 800 R Prednisone 60 mg/day reduced to 2.5 mg/day from Dec. 1972. X-ray: Dec. 1%0. 1800 R nasal field May 1961,’ 1 800 R nasal field Prednisone 40 mg/day Dec. 1960-May 1961
cells, interpreted as Wegener’s granulomatosis. X-ray showed atelectasis of the posterior basal segment in the left lung. Bronchoscopy: Papillomatous tumour occluding the lumen immediately peripheral to the opening of the apical bronchus of the left lower lung. Later he got haematuria, proteinuria, isosthenuria. Serum creatinine increased to 6.1 mg/dl. Creatinine-clearance fell to 29 ml/min. Biopsy of the kidneys showed proliferative and interstitial inflammatory changes and fibrinoid necrosis. Haemoptysis occurred. Rapidly deteriorating kidney failure followed. Serum electrophoresis showed increased alpha, and alpha, globulin and slightly increased immunoglobulin G and A. In June 1972, treatment started with Imurel 50 mg X 5, and prednisone 5 mg X 2, daily. Gradual improvement was obtained, and 5 months later the serum creatinine was 1.6 mg/dl. The creatinine clearance increased to 140 ml/min. A repeated biopsy from the kidney showed sclerosis of the glomeruli and great changes as compared to the first biopsy. Repeated X-ray showed almost normal lungs. Having been disabled for 14 years, he now returned to work and has later been fully employed. The lung function
Survival time following treatment
Effect Progression of disease Dead of bronchopneumonia
3 months Dead
16 months Progression of Dead disease Dead of lung abscess (May 1964) Great improvement. Full-time employed
30 months Alive
No improvement
8 months Dead
No improvement Dead 1.7.61
is normal. The administration of 10 mg prednisone and 225 mg Imurel daily has been continued. Case no. 7 (Table 11) A 41-year-old female nurse was admitted to Rikshospitalet in October 1972. Her complaints were: Since August 1972 pain in the left cheek radiating to the nose and nasal stuffiness on the left side. On admission, a swelling on the left cheek was found and the left eye was dislocated laterally. X-rays showed an infiltration in the left lung and exudate in the pleura. Later she had a bloodtinged nasal secretion. She presented a tumour-like infiltration in the nose. A biopsy specimen showed changes consistent with Wegener’s granulomatosis. She also had haematuria. The serum creatinine was 2.1 mg/ dl. She was ill and confined to bed. In November 1972, Imurel in a daily dose of 50 mg X 3 and prednisone, 10 mg x 3 , were administered. The general status rapidly improved and the X-ray changes in the lungs gradually decreased. SR decreased from 115 mm to 23 mm in the course of a few months. After 6 months, in the spring of 1973, she was again fully emAcIa OtoIaryngol82
210
H . Thorkelsen and P . Berdal
Downloaded by [Universität Osnabrueck] at 00:40 17 March 2016
Table 11. Wegener’s granulomatosis. Treatment with cytostatics Case no.
Profession Sex
1 LH
Glazier M
59
2 LJ
Upholsterer M
63
Age
3 TN
Typist F
28
4 A0
Shop girl F
65
5 LL
Factory worker 38
6 IJH
Housewife F
55
7 EHT
Nurse F
41
M
~~~~~~~~
Localisation of disease
SYmPt. duration (months)
Oral mucosa, skin of penis and face, lungs
96
Orbital tissue, kidneys,lungs
34
A. X-ray
B. Imurel 150 mg/day Prednisone 15 mg/day A. Prednisone 40 mg/day Imurel 150 mg/day B. Prednisone 80 mg/day Natulan 200 mglday Cyclophosphamid 1 000 mg i.v. weekly Vinblastin 10 mg i.v. weekly C. Cyclophosphamid 50 mg/ day oral. Prednisone 15 mg/day D. No cytostatics
Duration of treatment A. 1966,67,70,71 B. Last 3 months before death A. 6 months B. 3 sequenceseach of 2 weeks, interval 1 month
C. 2months
D. Last year of life 34 months continuous
Nasal and palatal mucosa. Skin of leg, tonsils Maxillary sinus, orbital tissues
36
Imurel200 mg/day Prednisone 60-10 mg/day
54
Imurel200 mg/day Prednisone 10 mglday
48 months
Nasal mucosa, lungs, joints, kidneys Lungs, kidneys
42
Imurel250 mg/day Prednisone 10 mglday
36 months continuous
4
Imurel75 mg/day Prednisone 80 mg/day
4 days prior to death of renal
Nasal mucosa and bone, lungs, kidneys
36
Imurel 150-300 mglday Prednisone 10-50 mglday
32 months continuous
failure
~
ployed. The local immune response, as studied by immunhistochemical methods, was not different from that of an unspecific chronic inflammation. The B and T lymphocytes studied by marker technique and in vitro function test were normal. The phagocytosis of the granulocytes was normal. The former patient is still fully employed (January 1976). During the past 1.5 years 11 patients with Wegener’s granulomatosis have been admitted to Rikshospitalet, the Ullevaal Hospital, and to the Nordland Sentralsykehus, B o b . Among these, 7 patients have been treated with Imurel and prednisone. The 4 other patients (Table I) were given X-rays and/or prednisone treatment. Before the diagnosis, all patients had antibiotic treatment because an infectious inflammation was suspected. The X-ray treatment had delayed the proActa Otolaryngol82
Treatment
gression of the disease. It has also reduced the pain, and the general health has improved. All in all, the palliative effect has been satisfactory. Imurel combined with prednisone has been administrated to 7 patients (Table 11). In 4 of the cases, this treatment had a very good effect, although the patients probably have not been cured. Two of these patients have already been discussed (patients 5 and 7). Imurel, 200-300 mg daily, has been given, and these patients have now been treated for 244; years. The treatment is continued. Side effects necessitating discontinuation of the treatment has occurred only once in a case in which Imurel treatment was stopped for 2 weeks due to leucopenia (2 OOO/mP). The treatment has later been continued for 8 months. Side effects of prednisone, like osteoporosis or moon face, have occasionally occurred. In
Wegener’s granulomatosis
Effect
Survival time following treatment
Good first years progression of disease
81 months Dead
No improvement
26 months Dead
No improvement
21 1
patients with advanced disease, but not hopeless so, a good palliative effect has been obtained. The manifestations in the kidneys, lungs and respiratory tract have improved. The side effects (leucopenia, osteoporosis) have been few and has not necessitated delay of the treatment except for a very short period. The treatment should be continued permanently.
Downloaded by [Universität Osnabrueck] at 00:40 17 March 2016
ZUSAMMENFASSUNG No improvement Progression of disease Improvement
33 months Alive
Great improvement. Full time employed
48 months Alive
Great improvement. Full time employed
36 months Alive
No improvement
8 days Dead
Great improvement. Full time emp1oy ed
31 months Alive
3 cases, there was no definite improvement after treatment with Imurel and prednisone. One reason for the lack of effect probably was that the disease had reached an advanced stage when the treatment was commenced. Wegener’s granulomatosis, like other diseases, may have different rates of progression and, consequently, show varying clinical manifestations in different patients. This may be one of the reasons why the results of the treatment vary. Another possibility is that there may be different types of the disease with special localisations and different rates of progression (lethal granuloma of the midline, Steward’s granuloma, malignant granuloma). The treatment of Wegener’s granulomatosis with Imurel and prednisone is based partly on theoretical and hypothetical pathogenetic considerations and partly on experience. In some
Es werden elf Patienten mit Wegeners Granulomatose erwahnt, von denen sieben mit Azathioprine (Imurel) kombiniert mit Prednison behandelt wurden. Vier dieser Patienten zeigten eine schnelle Verbesserung gleich nach Beginn der Behandlung. Atelektatische Lungenveranderungen verschwanden. Ein fortschreitendes Nierenversagen horte auf und die Nierenfunktion normalisierte sich. GroBere Hautschaden heilten aus. Die Behandlung hat inzwischen 24-44 Jahre gedauert und wurde nicht abgebrochen. Wir haben keine ernste Nebenwirkungen von Imurel gesehen. Man nimmt an, daB der gute Behandlungserfolg auf einer medikamentell hervorgerufenen immunosuppressiven Wirkung beruht.
REFERENCES Asin, H . R. G., Wagenaar, J. P. M. & Swierenga, J. 1972. The mitigated form of Wegener’s disease. Scand J Respir Dis 53, 367. Domarus, H. v. 1973. Wegenersche Granulomatose als Ursache fur Kiefer-Gesichts-Schmertzen. Z Laryngol Rhinol Otol52, 901. Gonzales, L. & Ordstrand, H. S. 1973. Wegener’s granulomatosis. Radiology 107, 295. Harrison, D. F. N. 1974. Non-healing granulomata of the upper respiratory tract. Br Med J ZV, 205. Host, H . 1973. Cytostatika og cytostatisk terapi. Tidsskr Nor Laegeforen 93, 1857. Jsrgensen, K. E. 1970. Immunosuppressiv behandling af Wegener’s granulomatose. Ugeskr Laeger 132, 1549. Linthicum, F. H. & Schwartzman, J. A. 1972. Wegener’s granulomatosis appearing initially as otitis media. Trans Am Acad Ophthalmol Otolaryngol72, 301. Moeschlin, S . 1969. Grenzen und Moglichkeiten der immunosuppressiven Therapie. Therapiwoche 19, 1 . Rmdam, P. & Hansen, L. A. 1971. Wegener’s granulomatosis. Dan Med Bull 18, 43. Shillitoe, E. J., Lehner, T., Lessof, M. H. & Harrison, D. F. N. 1974. Immunological features of Wegener’s granulomatosis. Lancet I , 281. Skevas, A. & Schmidt-Baumler. U. 1974. Die Behandlung der Wegenerschen Granulomatose mit Immunosuppressiva und Kortikosteroiden. Laryngol Rhinol 0101 (Stuttg) 53, 674. Teisberg, P. & Enger, E. 1970. Immunosuppressive therapy in Wegener’s granulomatosis. Acta Med Scand 187, 7 . Wegener’s granulomatosis. 1972. Lancet 11, 519. Acta Otolaryngol82
