A 41-year-old female consulted with 3-month history of pain in the sacroiliac region associated with arthralgias and myalgias of the lower limbs that partially improved with nonsteroidal anti-inflammatory drugs (NSAIDs). She denied cutaneous, digestive or ocular symptoms. An MRI of the sacroiliac joints showed subchondral bone marrow edema in both sacroiliac joints suggesting active sacroiliitis. A diagnosis of seronegative spondyloarthropathy with negative HLA-B27 was performed.
Two months later, she started Etanercept 50 mg administered subcutaneously once weekly, showing significant clinical improvement. After the third dose of the drug, she presented dry cough without expectoration and moderate effort dyspnea. She denied orthopnea, paroxysmal nocturnal dyspnea or upper respiratory symptoms. She had no chest pain, syncope or hemoptysis and did not refer digestive, genitourinary, cutaneous or neurological symptoms.
Her past medical history included two cesarean sections and a septorinoplasty. She denied previous exposure to tobacco or allergic diseases. In addition to Etanercept, she received vitamin D 2000 IU and Etoricoxib 90 mg daily. She had not traveled recently, did not have contact with animals, dust, particulate material or ill people.
The respiratory symptoms progressed rapidly. Thus, the patient consulted to the emergency department (ER). On admission to the ER, she was in acceptable general conditions, without signs of respiratory distress or requirement of supplementary oxygen at rest. Her blood pressure was 118/84 mmHg, pulse 96/bpm, respiratory rate 18/bpm, and weight 64.85Kg. She had no neck masses or jugular engorgement, the heart sounds were rhythmic without murmurs, the vesicular murmur was preserved in both lung fields. On pulmonary examination basal scanty pulmonary rales "Velcro"-like were auscultated. The abdomen had no masses, the extremities had neither edema nor inflammatory signs. The Tinel's sign was negative, Phalen's sign negative. Sacroiliac pain provocation tests were positive.
A high-resolution thoracic CT scan showed incipient ground-glass interstitial infiltrates of centrifugal distribution, especially involving the upper lobes. The EKG revealed a normal sinus rhythm. The transthoracic echocardiogram was normal without evidence of pulmonary hypertension. We decided to perform bronchoscopy with bronchoalveolar lavage (BAL), which showed a negative GeneXpert for Mycobacterium tuberculosis and a negative methenamine silver stain. Laboratory tests taken during admission revealed Hb 13 gr/dL, Hct 42%, leukocytes 4100/mm, neutrophils 2000/mm, lymphocytes 1400/mm, eosinophils 50/mm, platelets 325,000/mm, AST 29, ALT 23, total bilirubin 0.3, direct bilirubin 0.1, creatinine 0.6 and BUN 16.
A new high-resolution thoracic CT scan was performed. This scan showed a mosaic pattern of disseminated attenuation in both lungs with foci of ground glass infiltrates (Fig. 1 A, B, C). To dismiss the possibility of an infection a new bronchoscopy with a transbronchial biopsy was also performed. In the bronchoscopy, the aspect of the airway was normal, without endobronchial lesions or bleeding (Fig. 1 D), washing cytology showed a predominance of lymphocytes in 46% without the presence of malignant cells. The methenamine silver stain was negative. The pathology report showed the presence of rounded granulomas, composed of macrophages, epithelioid cells, multinucleated giant cells, and scarce lymphoplasmacytic infiltrate. No central necrosis or microorganisms were identified.
Based on the results obtained, we diagnosed acute toxicity by Etanercept presenting as granulomatous pneumonitis. Consequently, after a multidisciplinary evaluation, we decided to initiate pulses of methylprednisolone 500 mg for three days, continuing with an oral dose of prednisone 50 mg daily for twelve weeks. The dose was reduced progressively until reaching 12.5 mg daily with adequate tolerance and decrease of symptoms of cough and dyspnea.
Four weeks after starting the treatment with steroids, the patient was in an excellent general condition, without respiratory symptoms. A new high-resolution thoracic CT scan showed a notable decrease in the mosaic attenuation (Fig. 2 C, D). Two months later, she was in good clinical condition and had returned to work without new relapses nor respiratory symptoms.