A 38-year-old man, forest guard, resident of a hilly station of Himalayas, having schizophrenia for the past 15 years, being on antipsychotics: aripiprazole and trihexyphenidyl, presented to the emergency department with high-grade, intermittent fever for 7 days along with myalgia and headache. Following 4 days of fever, he developed multiple painless rashes over the soles of both feet and ankles. The rashes were reddish at the onset and later blackened. There was no gangrene formation or bleeding tendency. He reported breathlessness on exertion and later on in the supine position, but not paroxysmal nocturnal dyspnea. Breathlessness was associated with progressive bilateral leg edema and generalized weakness. He had decreased urine output for 1 day. There was no other history of any localizing symptoms. There was no history of substance use, alcohol intake, smoking, or any other comorbidity except above psychiatry illness. He was evaluated in an outside hospital where dengue NS1 antigen (on day 3 of illness) was positive along with low platelet count (40,000/mm3).
On examination, he was thin built but pale and edematous, afebrile, mildly drowsy, and disoriented. Vitals were unstable: heart rate 128 bpm, regular with satisfactory pulse volume; blood pressure 98/60 mm Hg with pulse pressure 48 mmHg; tachypneic (respiratory rate 30/min) with arterial oxygen saturation of 86% on ambient room air and 92%-95% on 4 L of O2 therapy (hypoxemia). Along with bilateral pitting pedal edema, there were multiple palpable but nontender purpuric rashes present on both feet ranging in size from 2 mm to 8 mm, with fine scaling and postinflammatory hyperpigmentation with confluence toward the terminal aspect and impending gangrene [Figure 1a]. All peripheral pulses were felt. Jugular venous pulse was not elevated. Chest examination demonstrated bilateral basal fine crackles and occasional wheezes. S1 and S2 were normal but with equal intensity (Tic-Tac rhythm like), and gallop/murmur was not present. Abdominal examination demonstrated mild tenderness over the right hypochondrium and epigastrium, but no palpable liver and spleen. Other systemic examinations were unremarkable.
From day 3 of admission (day 9 of illness), he started experiencing severe pain in both feet, which now showed darkening in color and was tender to touch, suggesting impending dry gangrene superimposed on the purpuric rashes [Figure 1a and b]. All peripheral arterial pulsations were normal, including the toe movements, and there was hyperesthesia of feet.
A probable diagnosis of EDS (because of outbreak season) with myocardium, vessels, skin, and kidney involvements was made.
Electrocardiography showed sinus tachycardia. Chest X-ray revealed features suggestive of early pulmonary edema [Figure 1d]. Initial arterial blood gas analysis showed compensated respiratory alkalosis. Hemogram on day 8 of the illness revealed anemia (Hb, 9.4 g/dL) with a normal mean corpuscular volume (MCV) and corrected reticulocyte count of 2.8, leukocyte count (7900/mm3), and thrombocytopenia (platelet count, 30,000/mm3) with a peripheral smear showing normochromic normocytic picture and reactive lymphocytes. Serum lactate dehydrogenase concentration was increased (457 U/L; reference normal <248 U/L in males). Erythrocyte sedimentation rate was 44 mm/h, and highly sensitive C-reactive protein fraction was 14.2 mg/L. Fibrin degradation products were 12 mg/L, and D-dimer was <0.5. ADAMTS13 levels, serum complement levels, and immunoglobulin levels could not be tested due to technical constraints and resource-limited setting. Kidney function tests suggested acute kidney injury. Liver function tests showed hyperbilirubinemia, predominantly conjugated (total bilirubin: 2.83 mg/dL/direct: 1.33 mg/dL), with mild transaminitis and hypoalbuminemia. NT pro-BNP levels were highly raised (3114.7 pg/mL; normal range <300 pg/mL); however, transthoracic echocardiogram did not reveal any abnormality. Blood cultures turned out to be sterile, and other infectious markers (malaria, scrub typhus, and chikungunya) were negative, except for dengue serology (ELISA-IgM). Serology for hepatitis B, hepatitis C, and human immunodeficiency virus was negative.
Doppler ultrasonography of both lower limbs demonstrated normal flow precluding arterial or venous occlusion. A skin biopsy was obtained from the area of purpuric rashes, which revealed foci in the upper dermis with perivascular infiltration by polymorphonuclear cells with mild edema and nuclear fragmentation, suggestive of leukocytoclastic vasculitis or CSVV [Figure 2a and b].
The final diagnosis of EDS with myocarditis, thrombotic microangiopathy, medium-vessel vasculitis (as impending peripheral gangrene), and CSVV (as purpura) was made.
He was given oxygen supplementation, titrated intravenous crystalloids, inotropic support (dobutamine), titrated diuretics, and other supportive measures. Intermittent continuous positive end-expiratory pressure support was given. Antipsychotic medications were withheld as per the advice by the psychiatrist. Antiplatelets were added after platelet counts were in the normal range.
Over the course of hospital stay, he improved symptomatically, tachycardia and respiratory distress settled, urine output increased with hydration, platelet counts improved, and features of purpura and impending gangrene improved. At the time of discharge, antipsychotic therapy was added as per the opinion of the psychiatrist. On follow-up visit after 7 days, his impending gangrene was not progressing and sloughing had started [Figure 1c], and he was followed up in the department of plastic surgery. Recently, in a follow-up after 2 months of dengue, he is doing his normal daily activities.