ARDS as a presenting feature in sarcoidosis: an uncommon occurrence

: Sarcoidosis though a chronic multi-system granulomatous disease, predominantly involves respiratory system. Often asymptomatic, patients can present with lymphadenopathy, prolonged fever and shortness of breath. Acute respiratory distress syndrome (ARDS) is relatively uncommon presenting feature of the disease. Here we present a case of a 19 years old female presenting in acute respiratory distress syndrome, eventually being diagnosed as Sarcoidosis. Although different diagnostic criteria have been developed for early diagnosis of sarcoidosis, atypical presentations can always pose significant challenge and lag for the diagnosis.


INTRODUCTION:
Sarcoidosis, a chronic granulomatous disease, can affect multiple organ systems. The etiology is largely unknown and it predominantly affects the respiratory system. Histological distinction of Sarcoidosis remains the presence of non-caseating granulomas in the affected organ. It was first reported by Jonathan Hutchinson in 1869 in a coal wharf worker who presented with skin lesions¹. Sarcoidosis, initially considered the disease of the developed countries, has now shown steady rise in the developing countries. Diagnosing sarcoidosis in developing countries remains difficult due to the overwhelming focus on infectious cause including tuberculosis. Atypical presentations such as ARDS and neurologic manifestations as the sole presenting feature make it even more difficult to reach a confirmative diagnosis.
Here we describe a case of a young female patient with sarcoidosis presenting as ARDS.

CASE:
A 19 years old female presented to the Out patient unit with the history of fever with chills and rigor for 10 days and shortness of breath for 3 days. She was initially evaluated at a primary center for tropical fever and was started on antimalarial and antibiotic. Despite initial therapy, her symptoms worsened and subsequently, she was referred to our center for further management.
At presentation, she had tachypnea, tachycardia and hypoxia (SpO2: 79% in room air). Examination revealed hepatosplenomegaly. Tropical disease screening for enteric fever, malaria, dengue, leptospirosis, brucellosis, and scrub typhus came negative. Blood culture was negative as well.
USG abdomen showed hepatosplenomegaly with periportal lymph node enlargement. Echocardiography was normal. Arterial blood gas revealed a pH of 7.36, PaCO2 of 44 mmHg and PaO2 of 58 mm Hg at FiO2 of 40%. High resolution computed tomography scan showed bilateral diffuse ground glass opacification with air space consolidation in bilateral lower lobes suggesting ARDS ( Figure 1). She was treated with high flow oxygen, antibiotics and steroids. With three 16hour sessions of awake self proning, she showed significant improvement in oxygenation as well as radiological clearance in HRCT scan. She was discharged on the 9th day of admission on oral steroid and antibiotics. Follow-up after a week was uneventful without new symptoms. The steroid was gradually tapered and stopped. NRJ | VOLUME 1 | NUMBER 1 | JANUARY-JUNE 2022 Unfortunately, two weeks later she presented in outpatient clinic with recurrence of fever and headache. Symptomatic management with antipyretic-analgesic didn't relieve her symptoms. Few days later, she landed in the emergency department disoriented and agitated. She had suffered an episode of generalized tonic clonic seizure. Emergency management was commenced immediately. Neurology consultation was done. CT scan of head didn't reveal any abnormal findings. She was admitted in high dependency unit. Her CSF analysis was normal. MRI brain done 24 hours later showed widespread multiple nodular lesions in the cerebrum, midbrain and cerebellum (figure 2). LDH level was normal. Her angiotensin converting enzyme level was significantly raised (125U/L). Bone marrow aspiration and biopsy examination showed non-caseating granulomas strongly suggestive of sarcoidosis ( figure 3). She showed significant improvement with steroids and newer generation antipsychotic and was discharged from hospital. Currently, she is in good remission with low dose of prednisolone, azathioprine and quetiapine and is under regular follow up at our respiratory and neurology clinic.

DISCUSSION:
Sarcoidosis can involve various organs with variable presentations in the respective organs ( Lungs are the most commonly affected organs in sarcoidosis 2,3 . However, ARDS as a presenting feature of sarcoidosis is a rare occurrence and only few cases have been documented in literature [4][5][6][7] . According to the Berlin criteria, our patient had moderate ARDS. Although it can be argued that the patient was not under any form of ventilation, literature review shows that spontaneous breathing patients can be recognized with ARDS at an early stage without positive pressure ventilation 8,9 .
Neurosarcoidosis is an uncommon but fatal complication of sarcoidosis 10,11 . Cranial nerve palsies are common presenting features and seizures complicates the clinical picture in almost 5-10 % of the cases 12,13 . Neurosarcoidosis requires compatible clinical findings with histologic demonstration of non-caseating granulomas and exclusion of other diseases. MRI usually shows leptomeningeal involvement however lobar involvement is rare 14 . MRI done in our patients showed multiple nodules all over the brain which warranted exclusion of other major possibilities such as tuberculosis and lymphoma. Bone marrow biopsy examination showed non-caseating granulomas. Normal CSF findings, significantly raised ACE levels and bone marrow biopsy revealing noncaseating granuloma lead the diagnosis of sarcoidosis with a diagnostic lag of 2 months. In retrospection, significant response of ARDS and neurological issues to steroids can be attributed to alveolar and neurosarcoidosis 15 .

CONCLUSION:
Sarcoidosis can present with wide range of, often unusual clinical features frequently leading to a significant diagnostic lag. ARDS remains a rare presenting feature of the disease.
Although different criteria have been developed for early diagnosis of sarcoidosis, biopsy remains the most confirmative option. Sound knowledge of the disease and detailed workup can lead to an early diagnosis and treatment.