CASE REPORT

Pulmonary Fibrosis Associated with Polymyalgia Rheumatica Tatsuya Shimada, Katsumi Matsumura, Kiichiro Higashi, Kenji Higashi, Keishi Kimura and Kimio Tomita*

Polymyalgia rheumatica (PMR)and exacerbated pulmonary fibrosis presented concurrently in a 69-year-old womanwith a 5-year history of idiopathic interstitial pneumonia. The radio- graphic and histological examinations suggested usual interstitial pneumonia (UIP) as a more likely diagnosis. therapy resulted in relief of the patient's muscle symptomsand improvement in the functional and radiographical signs of the pulmonary fibrosis. The final diagnosis was pulmonary fibrosis associated with PMR,because PMRis believed to be one of the causes contributing to interstitial lung diseases. (Internal Medicine 36: 837-840, 1997) Keywords: interstitial lung disease (ILD) , interstitial pneumonia, idiopathic interstitial pneumonia (IIP), usual interstitial pneumonia (UIP), (GCA)

Introduction On physical examination, her temperature was 37.4°C, pulse was 80 beats/min, and respiratory rate was 26 respirations/min. Polymyalgia rheumatica (PMR) has been reported by some She had muscular limitation of the and hip girdle authors to be self-limiting and associated with a good progno- motion due to pain, and fine crackles were audible in the lower sis. However, Mackenzie (1) reported cases of PMRcompli- two-thirds of both lung fields. cated by rheumatoid disease, , other inflammatory Laboratory data on admission were as follows : the hematocrit connective tissue diseases, and malignancies, although he re- was 37.0 percent; the white cell count was 9.1 x 109//, with 39 garded PMRas a working diagnosis from which the other percent neutrophils , 1 percent band forms, 3 percent eosinophils, diseases originate. Thorpe (2) reported that three of 1 1 patients 52 percent lymphocytes, and 5 percent monocytes. The eryth- with PMRhad vascular complications, and that PMRis a not so rocyte sedimentation rate (ESR) was 64 mm/h, serum lactate benign syndrome. Dent and Edwards (3) recognized a strong dehydrogenase (LDH) concentration 429 IU//, and C-reactive association between PMRand autoimmune thyroid diseases, protein level 0.3 mg/dl. The serum levels of muscle-derived which suggests the possibility of an immunological overlap enzymeswere within normallimits, and rheumatoidfactor and between these diseases, and since then other authors have antinuclear, anti-DNA, anti-ENA, and anti-Jo-1 antibodies reported PMRassociated with autoimmune thyroid diseases. were all negative. Aradiograph of her chest demonstrated a Wedescribe here a very rare case of exacerbated pulmonary honeycombpattern at the lung bases, a diffuse reticulonodular flbrosis associated with PMR,which is of interest because of pattern in the middle and upper lung field, and elevation of the clinical implications of the association between interstitial lung diaphragm (Fig. IB). The finding in the middle and upper lung disease (ILD) and PMR. field appeared more prominent than they had been when ini- tially observed in a prior radiograph performed 3 months earlier Case Report (Fig. 1A). Computed tomograph (CT) of the chest demon- strated a circumferential increase in density , suggesting fibrosing A 69-year-old womanwith a 5-year history of dyspnea was alveolitis, and thickening ofbronchovascular bundles (Fig. 2A, admitted to our hospital because of stiffness and aching in her B). Pulmonary function tests revealed a vital capacity (VC) of proximal muscles and dyspnea. She had been followed up for 0.97 liters (45% of predicted) and a single-breath carbon a suspected idiopathic interstitial pneumonia (IIP) as an outpa- monoxide diffusing capacity (Deo) of 6.94 ml/min/mmHg tient for 4 months. During the three months preceding admit- (52% of predicted). A specimen of arterial blood, drawn while tance, she had complained of stiffness and aching in the shoul- the patient was breathing ambient air, disclosed a partial pres- ders, , and hip girdles. sure of oxygen (PaO2) of 71.0 mmHg,the partial pressure of From the Department of Internal Medicine, KumamotoNational Hospital, Kumamotoand *the Third Department of Internal Medicine, KumamotoUniversity School of Medicine, Kumamoto Received for publication February 3, 1997; Accepted for publication June 20, 1997 Reprint requests should be addressed to Dr. Tatsuya Shimada, the Department of Internal Medicine, KumamotoNational Hospital, 1 -5 Ninomaru, Kumamoto 860

Internal Medicine Vol. 36, No. 1 1 (November 1997) 837 Shimada et al

Figure 1. Chest roentgenogram. Adiffuse reticulonodular pattern in the middle and upper lung field on chest roentgenogram obtained on admission (B) was observed in addition to the abnormal findings on a chest roentgenogram taken three months before admission (A).

Figure 2. Chest CT scan. A circumferential increase in intensity and thickening of bronchovascular bundles as shown on the CTsection through the middle lobes on admission (A) improved five years post-therapy (C). CTsections through the lower lobes show honeycombing patterns both on admission (B) and five years post-therapy (D), with post-therapy, there was mild amelioration of thickening of the bronchovascular bundles in the left lower lobe (D).

838 Internal Medicine Vol. 36, No. 1 1 (November 1997) Pulmonary Fibrosis with PMR carbon dioxide (PaCO2) of 42.8 mmHg, and pH of 7.39. A Oral prednisolone (40 mg daily) was initiated following a gallium-67 scan demonstrated diffuse uptake of the isotope diagnosis of exacerbated pulmonary fibrosis associated with throughout the lung parenchyma (Fig. 3). Histological exami- PMR.Twodays later, the stiffness and aching in the patient's nation of the specimens obtained at a transbronchial lung , neck, and hip girdles had promptly resolved. The biopsy (TBLB) showed a mildly fibrotic parenchyma with increased ESRand LDHconcentration normalized 18 days fibrous thickening of the alveolar wall, hyperplasia of type II following the therapy. Four weeks post-therapy, the pneumocytes, and partial hyalinization (Fig. 4). Temporal reticulonodular shadows in the middle and upper fields on the artery biopsy was not performed. chest radiograph disappeared, the pulmonary function tests showed improvements in her VC (1.4 liters; 65% of predicted) and Deo (7.9 1 ml/min/mmHg; 58% of predicted), and the PaO2 improved by 84.0 mmHg.The prednisolone dose was tapered over four months. Uponreduction of the prednisolone dose to 10 mgdaily, the patient's stiffness and aching recurred in the shoulders and hip girdles, that was soon corrected by increasing the dose to 15 mg daily, but no deteriorations on her chest radiographs were observed. Five years post-therapy, the cir- cumferential increase in density and thickening of bronchovascular bundles which were observed on the chest CT on admission improved (Fig. 2C, D). The maintenance pred- nisolone dose (10 to 15 mg daily) has been taken for over four years and four months with good control of symptomsand ESR, and without the occurrence of rheumatoid disease, vasculitis, other inflammatory connective tissue diseases, malignancies, or other complications. Discussion Lung involvement in patients with PMRis rare. It was necessary to distinguish two causes of lung involvement in the present PMRpatient; a primary process ofPMRand an associa- tion with PMR. Regarding the former, Karam and Fulmer (4) reported a 58-year-old womanwith PMRassociated with an ILD, the cause of which was identified as Figure 3. Gallium-67 scintigraphy on admission. (GCA). Furthermore, Bradley et al (5) reported that nodular Diffuse uptake of moderate intensity can be seen pulmonary lesions recurred twice following reduction of ste- throughout the lung. roid dose in a 59-year-old womanpresenting with PMR/GCA, and that these pulmonary lesions were a manifestation of either GCAor Wegener's granulomatosis. These two reports suggest that GCAis a primary lung involvement observed in patients with PMR/GCA.Since the pathologic lung findings in our PMR patient demonstrated no evidence of GCA,it was unlikely that a primary process of PMRwas the cause of lung involvement. Consequently, the cause of lung involvement in this PMR patient wasthought to be an association. Twocase reports have described overlapping lung involvement in patients with PMR. The first was that of a 65-year-old womanwith a 6-year history of GCAand PMRwho developed bronchiolitis-obliterans organizing pneumonia (BOOP)(6). The other was that of an 80- year-old womanwhoreceived for 10 months for PMRbut ultimately died of an accelerated form of usual interstitial pneumonia (UIP) (7). Thus, the present case repre- sents the third of an association between interstitial pneumonia Figure 4. Light microscopic picture of a specimen obtained and PMR. by transbronchial lung biopsy from the right B3a. Fibrous thick- Regarding the ILD in our case, a distinction had to be made ness of the alveolar wall and hyperplasia of type II pneumocytes amongUIP, BOOP,desquamative interstitial pneumonia (DIP) , are seen (HE stain, x80). lymphocytic interstitial pneumonia (LIP), and giant cell inter-

Internal Medicine Vol. 36, No. 1 1 (November 1997) 839 Shimada et al stitial pneumonia (GIP). The pathologic lung findings in this arthritis (10) or and (1 1). There- patient demonstrated no evidence of BOOP,DIP, LIP, or GIP, fore, it is possible that our patient's PMRwas preceded by which could all be diagnosed by TBLB. Radiographic exami- pulmonary fibrosis. nation can distinguish the nature of the infiltrates of BOOPand The association between pulmonary fibrosis and PMRin this UIP: BOOPis characterized by patchy air-space disease, and case as well as in the literature (6, 7) has important clinical UlP by small, irregular, and round opacities of a reticulonodular implications, because PMRshould be one of the causes consid- nature (7). The pathologic lung findings and the reticulonodular ered to contribute to ILD. Therefore, physicians should remain radiographic appearance in the present case suggested that UIP alert to the possibility of ILD occurring in PMRpatients. was the more likely candidate for lung involvement. Thus, the two most likely diagnoses were UIP by PMRand a chance References association between PMRand IIP, which presented as UIP. 1) Mackenzie AH. The polymyalgia rheumatica syndrome. Geriatrics 24: Because IIP or idiopathic pulmonary fibrosis (IPF) is in- 158, 1969. creasingly commonand PMRis also frequent, an association 2) ThorpeP. Polymyalgiarheumatica: anot so benign syndrome. MedJAust between PMRand IIP may well have occurred by chance. 2: 678, 1969. However,the prognosis and responsiveness to 3) Dent RG, Edwards OM. Autoimmune thyroid disease and the polymyalgia rheumatica-giant cell arteritis syndrome. Clin Endocrinol (Oxf) 9: 215, in patients with IPF are reportedly poor; respiratory failure 1978. occurs on average 5 years after the onset of symptoms,and only 4) KaramGH, Fulmer JD. Giant cell arteritis presenting as interstitial lung 10 to 20 percent of patients with IPF, particularly ones with disease. Chest 82: 781, 1982. early-stage IPF, improve with corticosteroids (8). In contrast, 5) Bradley JD, Pinals RS, Blumenfeld HB, Poston WM. Giant cell arteritis UIP caused by collagen-vascular disease has been reported to with pulmonary nodules. AmJ Med 77: 135, 1984. 6) Case Records of the Massachusetts General Hospital: weekly clinico- be relatively moreresponsive to corticosteroids (9). In the pathological exercises case 24-1986. N Engl J Med 314: 1627, 1986. present case, both PMRand pulmonary fibrosis were respon- 7) Case Records of the Massachusetts General Hospital: weekly clinico- sive to prednisolone even 5 years after the onset of respiratory pathological exercises case 19-1991. N Engl J Med 324: 1345, 1991. symptoms. Furthermore, the clinical course of pulmonary fi- 8) Crystal RG. Interstitial lung disease, in: Cecil Textbook of Medicine (19th ed), Wyngaarden JB, Smith Jr LH, Bennett JC, Eds. BWSaunders, brosis had lasted almost 10 years, yet a good response was Philadelphia, 1992, p. 396. observed. Therefore, this patient' s lung involvement was thought 9) Ishioka S. Clinical study of pulmonary complications in collagen dis- to be not merely an association ofIIP with PMR,but UIP caused eases. Nippon Naika Gakkai Zasshi (J Jpn Soc Intern Med) 83: 784, 1994 by PMR. (in Japanese). Unlike cases reported previously, PMRdeveloped follow- 10) Brannan HM, Good CA, Divertie MB, Baggenstoss AH. Pulmonary ing pulmonary fibrosis of only several years' duration in our disease associated with rheumatoid arthritis. JAMA189: 914, 1964. ll) Schwarz MI, Matthay RA, Sahn SA, Stan ford RE, Marmorstein BL, patient. Although collagen-vascular disease usually precedes Scheinhorn DJ. Interstitial lung disease in polymyositis and dermatomy- interstitial pneumonia,there have been a numberof reports of ositis: analysis of six cases and review of the literature. Medicine patients with collagen-vascular disease whodemonstrated in- (Baltimore) 55: 89, 1976. terstitial pneumoniaprior to the manifestations of rheumatoid

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