A 40-year-old Asian woman, non-smoker, housewife, presented in December, 2018 with progressive shortness of breath, initially only during physical exertion (i.e, walking upstairs) which later started occurring even at rest and a non-productive cough of three years duration which worsened in the ten days preceding presentation. She also complained of chest tightness during this presentation. She did not have a history suggestive of orthopnea or paroxysmal nocturnal dyspnea, swelling of her legs and/or body, fever, blood mixed sputum, chest pain or joints pain. She did not have exposure to patients with pulmonary tuberculosis. She had presented to an ophthalmologist 3 years back due to pain and redness of both eyes and was later diagnosed with bilateral granulomatous uveitis. She was treated with topical steroid for the same duration with intermittent intervals of as long as 2-3 months.
On examination, she was afebrile with a blood pressure of 130/80 mmHg in the right arm and heart rate was 80/minute. She had clubbing of her digits. Examination of peripheral pulses revealed absent pulse over the left radial and brachial arteries and feeble pulse over the right radial and brachial arteries, and bilateral carotid arteries. Carotid bruit was heard on the left side. Her oxygen saturation at room air was only 76% and required 4 liters/minute of oxygen to maintain 92% saturation (Normal >95%). Her jugular venous pressure was not raised and there was no pedal or sacral edema.
Laboratory parameters with normal ranges in parenthesis, are as follows:
Complete blood count: white cell count 4.2 (4-10) x 10^9/L; neutrophils 78%; lymphocytes 20%; red blood cells 4.6 (4.2-5.4) x 10^12/L; haemoglobin 13.3 (12-15) g/dL; platelets 244 (150-400) x 10^9/L.
Biochemistry: random blood sugar 126 (65-110) mg/dL; urea 29 (17-45) mg/dL; creatinine 0.9 (0.8-1.3) mg/dL; sodium 139 (135-145) mmol/L and potassium 4.3 (3.5-5) mmol/L.
Hepatic panel: bilirubin total 0.8 (0.1-1.2) mg/dL and direct 0.5 (0-0.4) mg/dL; alanine transaminase 39 (5-30) units/L; aspartate transaminase 45 (5-30) units/L; alkaline phosphatase 103 (50-100) IU/L; albumin 2.6 (3.5-5) g/dL
Erythrocyte sedimentation rate (ESR) was elevated at 45 mm/hr and c-reactive protein (CRP) was 4 mg/L (Normal < 10 mg/L). Angiotensin converting enzyme (ACE) levels were elevated at 186 u/L (Normal < 52 u/L); rheumatoid factor and anti-nuclear antibodies by indirect immunofluorescence were negative. Sputum examination did not reveal any organisms including acid fast bacilli. Sputum analysed by gene Xpert also did not detect Mycobacterium tuberculosis. The electrocardiogram was normal. Echocardiography showed moderate tricuspid regurgitation with moderate pulmonary arterial hypertension with a normal systolic function.
Chest X-ray ( Figure 1) revealed bilateral reticulo-nodular infiltrates involving the middle and lower zones and some parts of the upper zones. No changes were noted compared to a radiograph done three years ago. The pulmonary function test showed a restrictive pattern. High resolution computed tomography (CT) of the chest ( Figure 2) showed diffuse ground glass changes with interlobular septal thickening with mosaic attenuation and multiple enlarged calcified mediastinal and hilar lymph nodes (separate image of mediastinal section could not be retrieved). Bronchoscopy with trans-bronchial lung biopsy revealed non- caseating granulomatous inflammation with characteristic 'asteroid bodies' ( Figure 3 and Figure 4), and was negative for malignancy and tuberculosis. Hence the diagnosis of sarcoidosis (pulmonary and ocular) was made.
The findings of abnormal pulse led us to do a CT angiogram of aorta and its branches. Figure 5 shows stenosis of the left subclavian artery with almost complete block at the distal part as well as the proximal left axillary artery. Though images not available for the report, there was stenosis of right axillary, brachial artery and its branches, with sparing of abdominal aorta up to the lower extremities. This was suggestive of large vessel vasculitis in the upper extremities, Takayasu arteritis (Type I).
With the diagnosis of sarcoidosis with coexisting Takayasu arteritis, she was treated with prednisolone 60 mg once daily (1 mg/kg/day) along with supportive treatment including oxygen, chest physiotherapy, bone protection with calcium and vitamin D, and thromboembolism prophylaxis with daily 60 mg of subcutaneous enoxaparin. Ophthalmology examination showed bilateral granulomatous uveitis and was treated with topical prednisolone drops. She dramatically improved over 3-4 days and required only 1 liter/minute of oxygen support. Pneumococcal vaccination was administered. She was later discharged on domiciliary oxygen with a tapering prednisolone dosage.
After four weeks of discharge, while she was still on 30 mg of prednisolone, she developed blurring of vision. Ophthalmologic examination showed increased intraocular pressure with findings suggestive of Secondary glaucoma, probably steroid induced. Topical steroid was stopped and since oral steroid was to be tapered off quickly, azathioprine 50 mg/day was started as a steroid sparing immunosuppressant. Glaucoma was treated with topical timolol (0.25% twice daily) and oral acetazolamide (500 mg followed by 250 mg twice daily), and she responded well over the course of 2 weeks.
The patient is still on regular follow up (after 15 months of diagnosis) and is currently asymptomatic. She does not require oxygen and does not have symptoms of vasculitis (carotidynia, headache, lightheadedness, vertigo, tingling, numbness, limb claudication, cyanosis, arthralgias and skin lesions like erythema nodosum). She is currently taking azathioprine 50 mg/day, prednisolone 10 mg/day with calcium and vitamin D supplements. She is also on regular follow up every 3 months with a pulmonologist.
High-resolution computed tomography (HRCT) chest showing diffuse ground glass changes with interlobular septal thickening with mosaic attenuation and multiple enlarged calcified mediastinal and hilar lymph nodes.