å¡ CASE REPORT å¡ Bronchopulmonary Disease in Ulcerative Colitis Esteban Cesar Gabazza, Osamu Taguchi, Tomoya Yamakami, Motoko Machishi, Hidenori Ibata, Shigeo Fukukita, Kiyoyuki Tsutsui, Ichiro Imoto, Shiro Suzuki, Tatsushi Kitagawa*, Junji Yamamoto* and Koichi Matsumoto* Two cases of ulcerative colitis are described: a 33-year-old woman who developed wide spread bronchiectasis 7 months after undergoing colectomy, and a 72-year-old man whose colonic disease began coincidentally with the appearance of diffuse interstitial pulmonary infiltrates. In both cases, clinical correlation and common patterns of response of lung and bowel diseases suggested that the co-existence of these two pathologies might not be merely a casual relation. (Internal Medicine 31: 1155-1159, 1992) Key words: inflammatory bowel disease, lung involvement, lung interstitial disease, bronchiectasis per minute. Chest examination revealed diminished Introduction
respiratory excursion and coarse crackles more intense in both lung bases. Rhinological examination revealed
A broad spectrum of extra-intestinal manifestations can be associated with inflammatory bowel disease (1). Although pulmonary involvement is very rare, there were only six cases of unexplained bronchopulmonary disease in a review of 1,400 patients (2). However, re cently, a variety of airway-related disorders, interstitial and pleural diseases have been reported in ulcerative colitis (3-26). The occurrence of these complications underscores the fact that inflammatory bowel disease is a systemic illness. We herewith describe two new cases of lung disorders with underlying ulcerative colitis. Case Reports Case1 A 30-year-old woman, a non-smoker, had a 6-year history of ulcerative pancolitis which was being treated initially with sulfasalazine and prednisolone. Two years after persistent exacerbations of intestinal sympto matology she was admitted to Mie University Hospital Surgery Department where a total colectomy with pro tective loop ileostomy was carried out. Four months after her operation she started complaining of cough, purulent sputum (200- 300 ml/day) , dyspnea on exertion and anal bleeding. She was then admitted to our de
a chronic sinusitis. Laboratory data on admission were as follows: hemoglobin ll.9g/dl, white blood cell count 16.8 X 103/|li1, 0.83 segmented cells, 0.12 lymphocytes 0.04 monocytes and 0.01 eosinophils. The erythrocyte sedimentation rate was HOmm/h, C-reactive protein was 6mg/dl and cold hemagglutinins were positive at titer of 1:126. There was hypoalbuminemia with hyper immunoglobulinemia. The serum level of values: lactic dehydro The blood gas test revealed the following pH 7.48, genase 479IU/1 (Normalcarbon range:dioxide 100-230), and of oxygenwas pressure 62mmHg, 32mmHg alkaline phosphatase IU/1 (Normal range: and arterial saturation154 96%. Serological studies30-105). of anti nuclear antibody, rheumatoid factor and syphilis gave The conventional chest X-rayskin (Fig.test la)was revealed diffuse negative results. Tuberculin negative. reticulo-nodular shadows with bilateral lower zone bronchial thickening and dilated bronchi. The chest radiography before her operation was normal. The CT scanning (Fig. lb) showed bilateral and extensive bronchiectasis with micronodular shadowing in the inter stitium, more preponderant in the middle and the lower lobes. Gallium scanning disclosed diffuse irregular Pulmonary function test results (percentage of predicted distribution of the radioactive substance bilaterally. values) were the following: vital capacity 86.9% , forced
expiratory volume in one second 68%, DLco 62.8%. partment. The patient looked chronically ill. Her tem From the Third Department of Internal Medicine and *the Second Department of Surgery, Mie University School of Medicine, Mie perature pulseMarch rate 102 30Accepted respirations Receivedwas for39.5°C, publication 19, and 1992; for publication July 15, 1992. Reprint requests should be addressed to Dr. Esteban C Gabazza, the Third Department of Internal Medicine, Mie University School of Med Edobashi 2 cho-me 174, Tsu 514, Japan Internal
Medicine
Vol. 31, No. 9 (September
1992)
1155
Gabazza et al
Fig. 1. a) Chest thickening and dilated in the interstitium.
X-ray on admission of the first case, revealed diffuse reticulo-nodular shadows with bilateral bronchi in the lower bronchi, b) CT scanning showed extensive bronchiectasis with micronodular
bronchial shadowing
Fiberoptic bronchoscopic study showed bilateral bron chitis and the biopsic material taken during this procedure (Fig. 2) revealed thickness and fibrosis of the alveolar wall with lymphocyte and neutrophil infiltrations in the interstitium. She was treated with a regimen of postural drainage, antibiotics, prednisolone 30mg/day and sulfasalazine 4g/day. She responded satisfactorily to the therapy and was discharged with marked clinical and radiological improvements after one month (Fig. 3). Case2 A 72-year-old man was admitted to Mie University Fig. 2. Histological microphotograph (H.E.; x300) revealed thickness and fibrosis of the alveolar wall with interstitial lymphocyte and neutrophil infiltrations.
Fig. 3. a) left: first case, and b) right: second case. Improvement of chest radiological findings in both patients after one month of steroid therapy. 1156
Internal
Medicine
Vol. 31, No. 9 (September
1992)
Lung Involvement in Ulcerative
Colitis
Fig. 4. a) Chest X-ray of the second case showing diffuse infiltrates with predominant apical distribution, b) CT showing diffuse interstitial infiltrates and alveolar patchy shadows. Hospital because of persistent high fever, abdominal pain and melena. He was diagnosed as having ulcerative pancolitis by endoscopic, barium-enema and biopsic studies. Conventional chest X-ray on admission (Fig. 4a) showed diffuse infiltrates in both lungs with predominant apical distribution. The computerized tomography on admission (Fig. 4b) showed interstitial infiltrates and alveolar patchy shadows diffusely distributed in both lung fields. He was being treated irregularly with non steroidal antiinflammatory agents because of arthritis of the left knee and tarsometatarsal joints. There was no history of industrial exposure to dusts, chemical fumes or animals. Pulmonary symptomatology was absent. On examination the patient appeared chronically ill. The temperature was 39.0°C rectally, pulse rate 63 beats per minute and respirations 18/minute. Chest examination revealed a diffusely diminished breath sound in both
lung fields; moist rales were absent. There were no cyanosis, finger clubbing or edema. Laboratory data on admission included the following: hemoglobin 9.8 g/dl, white blood cell count 14.31 x 103//il, with 0.83 seg
mented cells, 0.13 lymphocytes, 0.02 monocytes and 0.02 eosinophils. The erythrocyte sedimentation rate Blood gas analysis the following pH, was 135mm/h, andrevealed the C-reactive protein,results: 15mg/dl. 7:45, oxygen pressure, 61.6mmHg; carbon dioxide pressure 35.2mmHg and oxygen saturation 91.5%. The serum albumin was low with hyperimmunoglobulinemia. Serum level of lactic dehydrogenase was 165 IU/1 (Normal range: 100-230), and of alkaline phophatase 208IU/1 (Normal range: 30- 105). Results of pulmonary function test were as follows: vital capacity 78% (percentage of predicted value), forced expiratory volume in one second 76%. Hemodynamic study revealed normal intracardiac pressures. Studies of antinuclear antibody, LE, rheumatoid factor, tests for syphilis and for viral infection were all negative. The tuberculin test produced no induration. Bronchoscopic study disclosed normal findings of both bronchial trees. Cytology and bacterio logical studies of the bronchial lavage were negative for malignant cells, acid-fast bacilli and bacteria. Histological examination (Fig. 5) of the transbronchial biopsy showed alveolar wall thickening, interstitial fibrosis with lym phocyte and histiocyte infiltrations. The patient was fol lowed up with sulfasalazine (4 g/day) and prednisolone (30mg/day) while work-up of his fever and lung abnor mality was carried out. Fever, colonic symptomatology Fig. 5. Histological examination disclosed alveolar thickening andand pulmonary infiltrates improved remarkably (Fib. 3b) interstitial fibrosis with mononuclear cell infiltrations (HE stain, after one month of therapy and the patient was discharged X300). from the hospital. He was followed up in the out-patient clinic where a gradual tapering of steroid and sulfasalaz 1157 Internal Medicine Vol. 31, No. 9 (September 1992) ing doses was initiated. Seven months later an acute
Gabazza et al deterioration of his ulcerative colitis without relapse of the interstitital disease occurred, necessitating the resumption of high daily doses of prednisolone therapy. He responded well again and over the sebsequent months he was given maintenance doses of prednisolone 10mg and sulfasalazine 3 g with good clinical evolution. Discussion Although numerous and varied systemic extraintestinal manifestations have been described during the course of inflammatory bowel disease, bronchopulmonary lesion is an infrequent complication of this disease (1-2). To date, including one case reported in the Japanese literature, there has been a total of 50 cases of pulmonary involvement in ulcerative colitis (3-26). The airway was the most commonly affected area with 33 cases (3-12). Interstitial pulmonary disease was diagnosed in 12 cases and pleuritis in the remaining 5 cases (13-26). Among the 33 reported cases of pulmonary involvement with airway disorders, there were 16 cases of bronchiectasis , 13 with suppurative bronchitis, 1 with fibrotic obliterative bronchitis, 1 with sclerosing peribronchiolitis, and an other case with diffuse panbronchiolitis (3-12). Women were more frequently affected than men, and age varied from 7 to 72 years old (4, 5). Cough and sputum were the most common symptoms that brought patients to consultation. Conventional chest X-ray disclosed infil trative and cystic shadowing more prominent at bases in 20 cases, at both lung apices in 1 and normal findings in 12 cases. Pulmonary function test was carried out in 31 patients; the obstructive or mixed pattern with diminished values of transfer factor for carbon monoxide were more commonly encountered. While in 12 patients the pulmonary symptomatology appeared after the sur gical treatment of the ulcerative colitis with an interval varying between 3 weeks and 12 years, in 5 cases the lung disease preceded the colonic presentation of inflam matory bowel disease (5, 6, 12). Other extraintestinal manifestations were also frequently found including arthritis in 9, skin lesions in 8, sinusitis and liver disease in 2 cases (3, 5, 7, 8). Twenty-three patients temporarily experienced clinical improvement with steroid therapy, whereas 2 patients improved after colectomy. The pre sent first case was a young woman who complained of cough with bronchial and sinus suppuration 7 months after a total colectomy, diffuse bronchi and granular shadows preponderantly basilar and with a functionally obstructive lung. Histological findings of the transbron choscopy biopsy were consistent with chronic interstitial pneumonia. Considering the time relationship between 1158 the exacerbation of her proctitis and the appearance of the pulmonary symptomatology, the lack of other
systemic manifestation associated with ulcerative colitis. To our knowledge interstitial lung disease has been reported in only 12 cases of ulcerative colitis (13-23). Among these cases, 6 presented pulmonary vasculitis, 6 diffuse interstitial lung fibrosis and another case of apical pulmonary fibrosis. Histological confirmation of the lesion was obtained in only 10 cases (13-15, 17-22). Of these, 2 cases showed pathological description com patible with Wegener's granulomatosis. Pulmonary fun ction test was performed in 5 cases, of which 4 presented characteristic restrictive pattern (19-23). Diverse chest radiological findings were described. Diffuse pulmonary infiltrates more conspicuous in the lower zones of the lungs were observed in 8 cases, bilateral pulmonary nodular lesions in 2, pleural effusion or thickening in 5 and unilateral apical pulmonary fibrosis in 1 case. In each of 8 patients there was a history of sulfasalazine therapy for their colonic affection. Of these , 6 patients were taking this drug when the pulmonary symptoms appeared, and though withdrawl of sulfasalazine was carried out, the pulmonary lesions did not regress (14, 20, 21). Pulmonary lesions did regress in 5 patients with the administration of corticosteroids, in 1 after the sur gical treatment of ulcerative colitis and in another case the improvement was spontaneous. In the second case of the current report, the pulmonary disorder commenced coincidentally with his ulcerative colitis and ameliorated The occurrence of pulmonary disorders in patients dramatically with the corticosteroid therapy. Our diag with inflammatory bowel disease poses a controversial nosis was ulcerative colitis-related lung interstitial disease. issue of whether these entities are truely associated or they only represent the casual occurrence of two unrelated disorders. In the current report, the onset of lung com plications paralleled flares of ulcerative colitis and, thus, favored the idea that true association might have existed between them. A review of the literature shows also the presence of temporal corrrelation between the states of activitiy of both diseases (3, 5, 9). Furthermore, in some of the reported cases, clinical and laboratory improvements were seen following colectomy as was mentioned before (5). The simultaneous beneficial effects of corticosteroid therapy for ulcerative colitis and pul monary lesion experienced in the present two cases and in others previously described, are likewise suggestive that they respond to the same etiopathogenetic mechanism The significance of the co-existence of these diseases (5,22). was also the object of various clinical investigations. Eade et al reported a significant reduction of carbon monoxide transfer factor as the only abnormality in inflammatory bowel disease patients in an age-matched control study. The results were not related to either sulfasalazine therapy or disease activity (27). Pasquis et al with a similar study design, found greater values of functional residual capacity during the attack than in Internal
Medicine
Vol. 31, No. 9 (September
1992)
Lung Involvement in Ulcerative
Colitis
remission of intestinal disease (28). It is also of interest to note that Bonniere et al found a persistent increased lymphocytosis in the bronchoalveolar lavage of those patients with normal clinical or radiological studies. The degree of this lymphocyte alveolitis was uncorrelated with abnormalities in functional tests of the lung (29). Based upon these studies, there appears to be a latent lung involvement that might somehow be linked to the changes occurring in the underlying bowel disease. The demonstration of this subclinical lung damage lays the basis for the hypothesis that both disorders might represent the expressions of the same systemic disease resulting from the host's response to a common etiological agent. In brief, considering the therapeutic and prognostic implications in the occurrence of lung disorders, we believe that there is justifiable rationale to advocate a periodical work-up for earlier diagnosis of this potential complication in inflammatory bowel disease patients, even though the pathogenetic mechanism of both dis orders as well as their interrelationship are, as yet, unestablished. New reports of cases with such as associ ation should encourage further investigation to enlighten this challenging aspect of inflammatory bowel disease. References
8) Pang JA, Vicary FR. Carcinoma of the colon, sclerosing chol angitis, pericholangitis, and bronchiectasis in a patient with ulcerative colitis. J Clin Gastroenterol 6: 361, 1984. 9) Gibb WRG, Dhillon DP, Zilkha KJ, Cole PJ. Bronchiectasis with ulcerative colitis and myelopathy. Thorax 42: 155, 1982. 10) Wilcox P, Miller R, Miller G, et al. Airway involvement in ulcerative colitis. Chest 92: 18, 1987. ll) Moles KW, Varghese G, Hayes JR. Pulmonary involvement in ulcerative colitis. Br J Dis Chest 82: 79, 1988. 12) Desai SJ, Gephardt GN, Stoller JK. Diffuse panbronchiolitis preceding ulcerative colitis. Chest 45: 1342, 1989. 13) Wasserman F, Krosnick A, Tumen H. Necrotizing angitis as sociated with chronic ulcerative colitis. Am J Med 17: 736, 1954. 14) Isenberg JI, Goldstein H, Korn AR, Ozeran RS, Rosen V. Pulmonary vasculitis an uncommon complication of ulcerative colitis. N Engl J Med 279: 1376, 1968. 15) Kedziora JA, Wolff M, Chang J. Limited form of Wegener's granulomatosis in ulcerative colitis. AJR 125: 127, 1975. 16) Forrest JAH, Shearman DJC. Pulmonary vasculitis and ulcerative colitis. Am J Dig Dis 20: 482, 1975. L7) Collins WJ, Bendig DW, Taylor WF. Pulmonary vasculitis com plicating childhood ulcerative colitis. Gastroenterology 77: 1091, 1979. L8) Sargent D, Sessions JT, Fairman RP. Pulmonary vasculitis complicating ulcerative colitis. South Med J 78: 624, 1985. L9) Turner-Warwick M. Fibrosing alveolitis and chronic liver disease. Q J Med 145: 133, 1968. 10) Mckee LA, Rajapakasa A, Kalish PE, Pitchumoni CS. Severe interstitial pulmonary fibrosis in a patient with chronic ulcerative colitis. Am J Gastroenterol 78: 86, 1983. ll) Teague WG, Sutphen JL, Fechner RE. Desquamative interstitial pneumonitis complicating inflammatory bowel disease of child 1) Greentein AJ, Janowitz HD, Sachar DB. The extra-intestinal hood. J Pediatr Gastroenterol Nutr 4: 663, 1985. manifestations of Crohn's disease and ulcerative colitis: a study 12) Balestra DJ, Balestra ST, Wasson JH. Ulcerative colitis and of 700 patients. Medicine 55: 401, 1976. steroid-responsive, diffuse interstitial lung disease. JAMA 260: 2) Rogers BHG, Clark LM, Kirsner JB. The epidemiologic and 62,1988. demographic characteristics of inflammatory bowel disease: '3) Meadway J. Ulcerative colitis, colitic spondylitis, and associated an analysis of a computerized file of 1,400 patients. J Chron Dis apical pulmonary fibrosis. Proc R Soc Med 67: 324, 1974. 24: 743, 1971. '4) Levin EN, Hirschfelt DS, Hersch RA. Pericarditis in association 3) Kraft SC, Earle RH, Roesler M, Esterly JR. Unexplained bron with ulcerative colitis. West J Med 130: 369, 1979. chopulmonary disease with inflammatory bowel disease. Arch \5) Patwarhan RV, Jeffrey-Heilpern R, Brewster AC, Darrah JJ. Intern Med 136: 454, 1976. Pleuro-pericarditis: an extraintestinal complication of inflam 4) Higenbottan T, Cochrane GM, Clark TJH, Turner D, Millis R,matory bowel disease: report of three cases and review of liter Seymour W. Bronchial disease in ulcerative colitis. Thorax 35: ature. Arch Intern Med 143: 94, 1983. 581, 1980. 6) Rosenbaum AJ, Murphy PJ, Engel JJ. Pleurisy during the course 5) Butland RJA, Cole P, Citron KM, Turner-Warwich M. Chronicof ulcerative colitis. J Clin Gastroenterol 5: 517, 1983. bronchial suppuration and inflammatory bowel disease. Q J Med7) Eade OE, Smith CL, Alexander JR, et al. Pulmonary function in 197: 63, 1981. with inflammatory bowel disease. Am J Gastroenterology 6) Shneerson JM. Lung bullae, bronchiectasis, and Hashimoto's patients 73; 154, disease associated with ulcerative colitis treated by colectomy. 8) Pasquis1980. P, Colin R, Denis PH, Baptiste P, Galmiche JP, Thorax 36: 313, 1981. Kecketsweiler PH. Transient pulmonary impairment during 7) Hiwatashi N, Konno Y, Kobayashi K, Goto Y. Ulcerative colitis attacks of Crohn's disease. Respiration 41: 56, 1981. with chronic bronchial suppuration-report of a case. Japanese 9) Bonniere P, Wallaert B, Cortot A, et al. Latent pulmonary Journal of Colon Diseases 36: 129, 1983 (in Japanese). involvement in Crohn's disease: biological, functional broncho alveolar lavage and scintigraphic studies. GUT 27: 919, 1986.
Internal
Medicine
Vol. 31, No. 9 (September
1992)
1159
respiratory excursion and coarse crackles more intense in both lung bases. Rhinological examination revealed
A broad spectrum of extra-intestinal manifestations can be associated with inflammatory bowel disease (1). Although pulmonary involvement is very rare, there were only six cases of unexplained bronchopulmonary disease in a review of 1,400 patients (2). However, re cently, a variety of airway-related disorders, interstitial and pleural diseases have been reported in ulcerative colitis (3-26). The occurrence of these complications underscores the fact that inflammatory bowel disease is a systemic illness. We herewith describe two new cases of lung disorders with underlying ulcerative colitis. Case Reports Case1 A 30-year-old woman, a non-smoker, had a 6-year history of ulcerative pancolitis which was being treated initially with sulfasalazine and prednisolone. Two years after persistent exacerbations of intestinal sympto matology she was admitted to Mie University Hospital Surgery Department where a total colectomy with pro tective loop ileostomy was carried out. Four months after her operation she started complaining of cough, purulent sputum (200- 300 ml/day) , dyspnea on exertion and anal bleeding. She was then admitted to our de
a chronic sinusitis. Laboratory data on admission were as follows: hemoglobin ll.9g/dl, white blood cell count 16.8 X 103/|li1, 0.83 segmented cells, 0.12 lymphocytes 0.04 monocytes and 0.01 eosinophils. The erythrocyte sedimentation rate was HOmm/h, C-reactive protein was 6mg/dl and cold hemagglutinins were positive at titer of 1:126. There was hypoalbuminemia with hyper immunoglobulinemia. The serum level of values: lactic dehydro The blood gas test revealed the following pH 7.48, genase 479IU/1 (Normalcarbon range:dioxide 100-230), and of oxygenwas pressure 62mmHg, 32mmHg alkaline phosphatase IU/1 (Normal range: and arterial saturation154 96%. Serological studies30-105). of anti nuclear antibody, rheumatoid factor and syphilis gave The conventional chest X-rayskin (Fig.test la)was revealed diffuse negative results. Tuberculin negative. reticulo-nodular shadows with bilateral lower zone bronchial thickening and dilated bronchi. The chest radiography before her operation was normal. The CT scanning (Fig. lb) showed bilateral and extensive bronchiectasis with micronodular shadowing in the inter stitium, more preponderant in the middle and the lower lobes. Gallium scanning disclosed diffuse irregular Pulmonary function test results (percentage of predicted distribution of the radioactive substance bilaterally. values) were the following: vital capacity 86.9% , forced
expiratory volume in one second 68%, DLco 62.8%. partment. The patient looked chronically ill. Her tem From the Third Department of Internal Medicine and *the Second Department of Surgery, Mie University School of Medicine, Mie perature pulseMarch rate 102 30Accepted respirations Receivedwas for39.5°C, publication 19, and 1992; for publication July 15, 1992. Reprint requests should be addressed to Dr. Esteban C Gabazza, the Third Department of Internal Medicine, Mie University School of Med Edobashi 2 cho-me 174, Tsu 514, Japan Internal
Medicine
Vol. 31, No. 9 (September
1992)
1155
Gabazza et al
Fig. 1. a) Chest thickening and dilated in the interstitium.
X-ray on admission of the first case, revealed diffuse reticulo-nodular shadows with bilateral bronchi in the lower bronchi, b) CT scanning showed extensive bronchiectasis with micronodular
bronchial shadowing
Fiberoptic bronchoscopic study showed bilateral bron chitis and the biopsic material taken during this procedure (Fig. 2) revealed thickness and fibrosis of the alveolar wall with lymphocyte and neutrophil infiltrations in the interstitium. She was treated with a regimen of postural drainage, antibiotics, prednisolone 30mg/day and sulfasalazine 4g/day. She responded satisfactorily to the therapy and was discharged with marked clinical and radiological improvements after one month (Fig. 3). Case2 A 72-year-old man was admitted to Mie University Fig. 2. Histological microphotograph (H.E.; x300) revealed thickness and fibrosis of the alveolar wall with interstitial lymphocyte and neutrophil infiltrations.
Fig. 3. a) left: first case, and b) right: second case. Improvement of chest radiological findings in both patients after one month of steroid therapy. 1156
Internal
Medicine
Vol. 31, No. 9 (September
1992)
Lung Involvement in Ulcerative
Colitis
Fig. 4. a) Chest X-ray of the second case showing diffuse infiltrates with predominant apical distribution, b) CT showing diffuse interstitial infiltrates and alveolar patchy shadows. Hospital because of persistent high fever, abdominal pain and melena. He was diagnosed as having ulcerative pancolitis by endoscopic, barium-enema and biopsic studies. Conventional chest X-ray on admission (Fig. 4a) showed diffuse infiltrates in both lungs with predominant apical distribution. The computerized tomography on admission (Fig. 4b) showed interstitial infiltrates and alveolar patchy shadows diffusely distributed in both lung fields. He was being treated irregularly with non steroidal antiinflammatory agents because of arthritis of the left knee and tarsometatarsal joints. There was no history of industrial exposure to dusts, chemical fumes or animals. Pulmonary symptomatology was absent. On examination the patient appeared chronically ill. The temperature was 39.0°C rectally, pulse rate 63 beats per minute and respirations 18/minute. Chest examination revealed a diffusely diminished breath sound in both
lung fields; moist rales were absent. There were no cyanosis, finger clubbing or edema. Laboratory data on admission included the following: hemoglobin 9.8 g/dl, white blood cell count 14.31 x 103//il, with 0.83 seg
mented cells, 0.13 lymphocytes, 0.02 monocytes and 0.02 eosinophils. The erythrocyte sedimentation rate Blood gas analysis the following pH, was 135mm/h, andrevealed the C-reactive protein,results: 15mg/dl. 7:45, oxygen pressure, 61.6mmHg; carbon dioxide pressure 35.2mmHg and oxygen saturation 91.5%. The serum albumin was low with hyperimmunoglobulinemia. Serum level of lactic dehydrogenase was 165 IU/1 (Normal range: 100-230), and of alkaline phophatase 208IU/1 (Normal range: 30- 105). Results of pulmonary function test were as follows: vital capacity 78% (percentage of predicted value), forced expiratory volume in one second 76%. Hemodynamic study revealed normal intracardiac pressures. Studies of antinuclear antibody, LE, rheumatoid factor, tests for syphilis and for viral infection were all negative. The tuberculin test produced no induration. Bronchoscopic study disclosed normal findings of both bronchial trees. Cytology and bacterio logical studies of the bronchial lavage were negative for malignant cells, acid-fast bacilli and bacteria. Histological examination (Fig. 5) of the transbronchial biopsy showed alveolar wall thickening, interstitial fibrosis with lym phocyte and histiocyte infiltrations. The patient was fol lowed up with sulfasalazine (4 g/day) and prednisolone (30mg/day) while work-up of his fever and lung abnor mality was carried out. Fever, colonic symptomatology Fig. 5. Histological examination disclosed alveolar thickening andand pulmonary infiltrates improved remarkably (Fib. 3b) interstitial fibrosis with mononuclear cell infiltrations (HE stain, after one month of therapy and the patient was discharged X300). from the hospital. He was followed up in the out-patient clinic where a gradual tapering of steroid and sulfasalaz 1157 Internal Medicine Vol. 31, No. 9 (September 1992) ing doses was initiated. Seven months later an acute
Gabazza et al deterioration of his ulcerative colitis without relapse of the interstitital disease occurred, necessitating the resumption of high daily doses of prednisolone therapy. He responded well again and over the sebsequent months he was given maintenance doses of prednisolone 10mg and sulfasalazine 3 g with good clinical evolution. Discussion Although numerous and varied systemic extraintestinal manifestations have been described during the course of inflammatory bowel disease, bronchopulmonary lesion is an infrequent complication of this disease (1-2). To date, including one case reported in the Japanese literature, there has been a total of 50 cases of pulmonary involvement in ulcerative colitis (3-26). The airway was the most commonly affected area with 33 cases (3-12). Interstitial pulmonary disease was diagnosed in 12 cases and pleuritis in the remaining 5 cases (13-26). Among the 33 reported cases of pulmonary involvement with airway disorders, there were 16 cases of bronchiectasis , 13 with suppurative bronchitis, 1 with fibrotic obliterative bronchitis, 1 with sclerosing peribronchiolitis, and an other case with diffuse panbronchiolitis (3-12). Women were more frequently affected than men, and age varied from 7 to 72 years old (4, 5). Cough and sputum were the most common symptoms that brought patients to consultation. Conventional chest X-ray disclosed infil trative and cystic shadowing more prominent at bases in 20 cases, at both lung apices in 1 and normal findings in 12 cases. Pulmonary function test was carried out in 31 patients; the obstructive or mixed pattern with diminished values of transfer factor for carbon monoxide were more commonly encountered. While in 12 patients the pulmonary symptomatology appeared after the sur gical treatment of the ulcerative colitis with an interval varying between 3 weeks and 12 years, in 5 cases the lung disease preceded the colonic presentation of inflam matory bowel disease (5, 6, 12). Other extraintestinal manifestations were also frequently found including arthritis in 9, skin lesions in 8, sinusitis and liver disease in 2 cases (3, 5, 7, 8). Twenty-three patients temporarily experienced clinical improvement with steroid therapy, whereas 2 patients improved after colectomy. The pre sent first case was a young woman who complained of cough with bronchial and sinus suppuration 7 months after a total colectomy, diffuse bronchi and granular shadows preponderantly basilar and with a functionally obstructive lung. Histological findings of the transbron choscopy biopsy were consistent with chronic interstitial pneumonia. Considering the time relationship between 1158 the exacerbation of her proctitis and the appearance of the pulmonary symptomatology, the lack of other
systemic manifestation associated with ulcerative colitis. To our knowledge interstitial lung disease has been reported in only 12 cases of ulcerative colitis (13-23). Among these cases, 6 presented pulmonary vasculitis, 6 diffuse interstitial lung fibrosis and another case of apical pulmonary fibrosis. Histological confirmation of the lesion was obtained in only 10 cases (13-15, 17-22). Of these, 2 cases showed pathological description com patible with Wegener's granulomatosis. Pulmonary fun ction test was performed in 5 cases, of which 4 presented characteristic restrictive pattern (19-23). Diverse chest radiological findings were described. Diffuse pulmonary infiltrates more conspicuous in the lower zones of the lungs were observed in 8 cases, bilateral pulmonary nodular lesions in 2, pleural effusion or thickening in 5 and unilateral apical pulmonary fibrosis in 1 case. In each of 8 patients there was a history of sulfasalazine therapy for their colonic affection. Of these , 6 patients were taking this drug when the pulmonary symptoms appeared, and though withdrawl of sulfasalazine was carried out, the pulmonary lesions did not regress (14, 20, 21). Pulmonary lesions did regress in 5 patients with the administration of corticosteroids, in 1 after the sur gical treatment of ulcerative colitis and in another case the improvement was spontaneous. In the second case of the current report, the pulmonary disorder commenced coincidentally with his ulcerative colitis and ameliorated The occurrence of pulmonary disorders in patients dramatically with the corticosteroid therapy. Our diag with inflammatory bowel disease poses a controversial nosis was ulcerative colitis-related lung interstitial disease. issue of whether these entities are truely associated or they only represent the casual occurrence of two unrelated disorders. In the current report, the onset of lung com plications paralleled flares of ulcerative colitis and, thus, favored the idea that true association might have existed between them. A review of the literature shows also the presence of temporal corrrelation between the states of activitiy of both diseases (3, 5, 9). Furthermore, in some of the reported cases, clinical and laboratory improvements were seen following colectomy as was mentioned before (5). The simultaneous beneficial effects of corticosteroid therapy for ulcerative colitis and pul monary lesion experienced in the present two cases and in others previously described, are likewise suggestive that they respond to the same etiopathogenetic mechanism The significance of the co-existence of these diseases (5,22). was also the object of various clinical investigations. Eade et al reported a significant reduction of carbon monoxide transfer factor as the only abnormality in inflammatory bowel disease patients in an age-matched control study. The results were not related to either sulfasalazine therapy or disease activity (27). Pasquis et al with a similar study design, found greater values of functional residual capacity during the attack than in Internal
Medicine
Vol. 31, No. 9 (September
1992)
Lung Involvement in Ulcerative
Colitis
remission of intestinal disease (28). It is also of interest to note that Bonniere et al found a persistent increased lymphocytosis in the bronchoalveolar lavage of those patients with normal clinical or radiological studies. The degree of this lymphocyte alveolitis was uncorrelated with abnormalities in functional tests of the lung (29). Based upon these studies, there appears to be a latent lung involvement that might somehow be linked to the changes occurring in the underlying bowel disease. The demonstration of this subclinical lung damage lays the basis for the hypothesis that both disorders might represent the expressions of the same systemic disease resulting from the host's response to a common etiological agent. In brief, considering the therapeutic and prognostic implications in the occurrence of lung disorders, we believe that there is justifiable rationale to advocate a periodical work-up for earlier diagnosis of this potential complication in inflammatory bowel disease patients, even though the pathogenetic mechanism of both dis orders as well as their interrelationship are, as yet, unestablished. New reports of cases with such as associ ation should encourage further investigation to enlighten this challenging aspect of inflammatory bowel disease. References
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