A 42-year-old HIV-positive Zambian woman of African descent presented to the emergency department with a 7-month history of anorexia, progressive dyspnoea, and a productive cough with mucoid sputum. The patient had a history of receiving at least 6 months of anti-tuberculosis treatment (ATT) from her referring hospital based on symptoms and chest radiographic findings, without any significant clinical improvement. In addition, she received high-dose co-trimoxazole for suspected Pneumocystis jiroveci pneumonia (PCP) which was also without notable effect. At the time of presentation, she had been on combined anti-retroviral treatment (cART) for about 6 years. She denied any history of rash, joint pains, headaches, or photophobia. On examination, she appeared ill, was fully conscious, apyrexic, tachypneic (32 breaths per minute), and tachycardic (120 beats per minute) with a peripheral oxygen saturation of 84% on ambient air and a blood pressure of 110/70 mmHg. On auscultation, coarse extensive crackles were heard in both lung fields and the heart sounds were regular with a loud P2 noted in the tricuspid area. The examination was negative for any skin rash, alopecia, joint swelling/deformity, hepatosplenomegaly, ascites, or peripheral edema. An initial electrocardiogram showed a sinus tachycardia with left axis deviation, right ventricular strain pattern with T wave inversion in V1–V4 as well as lead III, and prominent R wave in right-sided leads which were in keeping with right ventricular hypertrophy. Her chest X-ray showed an enlarged cardiac shadow with air bronchograms and diffuse reticular shadowing. An urgent transthoracic echocardiogram revealed a mild pericardial effusion, right atrial and right ventricular enlargement with tricuspid regurgitation, and pulmonary hypertension. Initial blood gases showed a picture of hypoxemia with low arterial carbon dioxide consistent with type 1 respiratory failure pattern (PH 7.46, PCO2-27 mmHg; expected compensation of 34–38 mmHg by Winters’ equation, PO2-42 mmHg, HCO3-18.7 mEq/L). D-dimers were markedly elevated at 2600 ng/mL. Despite the highly elevated d-dimer levels, the follow-up chest CT was negative for pulmonary embolism, and the findings were reported as normal. A Doppler ultrasound of both lower limbs excluded venous thromboembolism. Her abdominal ultrasound scan was also normal. Sputum for Gene-Xpert, microscopy, culture, and sensitivity were obtained to exclude other infectious etiology. The working diagnosis at this point was subacute pulmonary embolism (PE) to exclude chronic infectious pneumonia. The patient received high-flow oxygen at 8 L/min via face mask, low-molecular weight heparin (enoxaparin 80 mg twice daily), warfarin (5 mg once daily), and furosemide 40 mg once daily in view of extensive fine crackles in both lung fields. Results of the investigations performed are shown in the table below. The patient improved during the course of admission. She was no longer oxygen dependent, her SaPO2 was 94% on ambient air, the lung fields were clear on auscultation, and there was a reduction in her respiratory rate to 24/min. Her sputum investigations for tuberculosis and bacterial infection were negative. She was discharged on day 9 based on the pulmonary embolism severity index (PESI) low-risk score on warfarin 5 mg once daily, pending laboratory results for repeat d-dimers. However, she was readmitted 5 days later due to the recurrence of severe respiratory distress. On re-admission, she was very restless, breathless at rest, and apyrexic. She was neither pale nor cyanosed. Her peripheral saturation was 98% on 4 L/min of oxygen via the nasal cannula. She had no features of fluid overload. The lung fields were clear on auscultation but of note was a pericardial rub and loud P2. Meanwhile, repeat transthoracic echocardiogram showed a mild pericardial effusion and pulmonary hypertension. An electrocardiogram was repeated and had features consistent with the first one done on the initial admission. There was normalization of her d-dimers (396 ng/mL). However, the test results for autoimmune diseases showed a strongly positive ANA and anti-dsDNA. Anti-histone and anti-phospholipid antibodies (anti-β2 glycoprotein 1, lupus anticoagulant, and anti-cardiolipin antibodies) were negative. Based on the results, a diagnosis of active SLE with a possibility of chronic lupus interstitial lung disease was made. The patient was admitted in a high dependency ward for further treatment and support. She received intravenous methylprednisolone 500 mg stat, then 250 mg once daily for 4 days followed by oral prednisolone 50 mg once daily. She also continued her warfarin therapy. She was discharged 11 days later in an asymptomatic state on prednisolone, hydroxychloroquine, omeprazole, and warfarin. On her scheduled review in the rheumatology clinic a fortnight later, she remained asymptomatic and a slow tapering down of prednisolone was begun. She continued to live a normal life. In view of her HIV status and steroid use, routine immunological assessment was scheduled for every 3 months as well as monthly medical reviews for warfarin therapy and INR monitoring.