A patient with rheumatoid arthritis...

A patient with rheumatoid arthritis unfolded restrictive lung disease and life-blood eosinophilia. Gold pneumonitis was suspected however the patient did not improve until naproxen was discontinued as well. Lymphocyte transformation studies hinted hypersensitivity to gold. We hypothesize that naproxen unmasked and perpetuated the manifestations of gold hypersensitivity in our patient.

(Chest 1989; 96:216-18)

Gold salts are a well-recognized cause of toxic pneumonitis.[1-4] Diffuse pulmonary infiltrates have also been occasionally reported in individuals taking NSAIDs.[5-9] Since interstitial lung disease can be associated with rheumatoid arthritis (RA) alone, the first brunt of pneumonitis in an RA patient receiving gold and NSAIDs exhibits a difficult diagnostic dilemma. In a late patient, there was evidence that the couple pharmacologic agents used in treatment actually interacted to bring a significant, but reversible, pulmonary injury.

Case Report

A 62 year-old man disentangleed seropositive RA in 1984 and was treated with various NSAIDs. Chrysotherapy was initiated in May 1986 and he received a total of 685 mg SATM above three months when the physic had to be discontinued because of mucodermatitis. Naproxen, 500 mg twice daily, had been started in July 1986 About this time, he began to complain of malaise, fatigue, anorexia, and a nocturnal cough above the next four weeks, his cough became continuous, he unfolded mild dyspnea and chest tightness, and thrown away 6.8 kg in weight. Chest roentgenogram revealed bilateral apical airspace consolidation and pulmonary function studies demonstrated a restrictive ventilatory deficiency Flexible fiberoptic bronchoscopy with transbronchial biopsy was performed and this revealed an eosinophil-predominant alveolitis.

in succession transfer to our hospital, the patient had experienced one improvement in his cough and dyspnea. Examination showed fine bibasilar inspiratory crackles and joint changes consistent with RA. The WBC consider was 10.1 x [10.sup.9]/L with >900 eosinophils/ml. The ESR (Wintrobe) was elevated at 51 mm/hr and rheumatoid factor was positive at 1070 KU/L (normal <60) Chest roentgenogram revealed a predominantly upper lobe acinar and interstitial infiltrate. Pulmonary function studies confirmed a restrictive ventilatory pattern with a normal [FEVsub1]/FVC of 95 percent if it be not that static lung volumes of 65 to 75 percent of predicted and a Dco of 63 percent of predicted. the two gallium and NMR scans put in mind ofed active alveolitis; bronchoalveolar lavage was not performed. Our diagnosis was gold pneumonitis, and we chooseed to watch the patient closely without further intervention.

The following week, symptoms and examination were unchanged, further both chest roentgenogram and pulmonary function studies had deteriorated. He had been left upon naproxen for symptomatic control, and this was discontinued. Thereafter, he underwent a dramatic regaining with resolution of all symptoms and spontaneous improvement in chest x-ray film and pulmonary function; the same month later, these studies were normal, and his peripheral eosinophilia had resolved

united month later, because of an exacerbation of his RA, methotrexate, 75 mg weekly, was added to ibuprofen therapy. Three month later, he exhibited profound thrombocytopenia (platelets <10 x [10sup9]/L) and this persisted despite discontinuing the methotrexate. Bone marrow examination eventuate was normal. Immune thrombocytopenia fit to SATM was suspected, and the platelet estimate normalized promptly on prednisone, 5 mg four times a day.

In Vitro Studies

In an effort to determine the etiology of what appeared to be a hypersensitivity pneumonitis, in vitro studies fancy to be relatively predictive of cell-mediated immunity to pharmacologic agents were performed.[10-13] Briefly, PBMC harvested from Ficoll-Hypaque cushions were obtained from the patient and three healthy male offers The PBMC from the patient were cultur in the personality of media alone (control), mitogen (1 percent PHA), and various concentrations of naproxen and SATM with or without PHA. After 48 hours, the cultivations were supplemented with tritiated thymidine, and the nearest day the cells were harvested and the proliferative answer determined by the specific [TABULAR DATA OMITTED] uptake of radiolabel. Shown in Figure 1 are the arises from one of the healthy enslaves (the other two behaving in an identical fashion). While neither naproxen or SATM ([10sup-4] or [10sup-6] M) had any event on the basal proliferative capacity of the solitary abode; squalids both agents had inhibitory meanings with PHA-treated cells. When proofed individually [10.sup.-4] M naproxen reduc thymidine uptake by dint of 8.5 percent (not significant), and [10sup-4] SATM according to 35 percent (p<0.02); in combination, the validitys appeared to be additive, with [10sup-4] M of one as well as the other naproxen and SATM reducing the proliferative reply by 45 percent (p<0.005).

The patient's lymphocyte also were unaffected from naproxen alone but displayed a proliferative reply to SATM (Table 1). In contrast to the confined apartments from the healthy subjects, there was a mild stimulation of proliferation with SATM alone, and a dramatic accentuation onward exposure of the lymphocytes to PHA plus naproxen, and particularly PHA plus SATM. Unfortunately, the combination of SATM and naproxen could not be evaluated in our patient.