Strongyloides stercoralis hyperinfection in patient with autoimmune hepatitis and purpura fulminans.

Strongyloidiosis is usually an asymptomatic chronic nematodal disease. The term hyperinfection is used to denote autoinfection, a phenomenon in which the number of worms increases enormously. Development or exacerbation of gastrointestinal and pulmonary symptoms is seen, (A) and the detection of increased numbers of larvae in stool and or sputum is the hallmark. It is known to occur with a change in immune status of the host; this can occur due to immunosuppressants. Cytomegalovirus (CMV) is also known to suppress host immunity. Due to the nonspecific presentation, the diagnosis is frequently missed, and the outcome remains poor with 15-87% mortality despite therapy. We report here a case of Strongyloides stercoralis hyperinfection following immunosuppressive therapy for autoimmune hepatitis and concomitant CMV infection with purpura fulminance and frank sepsis, with fatal outcome.

Introduction

Strongyloides hyperinfection is a well-known entity; however this is the first case report of a North Indian patient with autoimmune hepatitis and purpura fulminance. In India, the epicenter lies in southern states, with a paucity of cases reports from northern states.[1] To our knowledge, this is the first case report of strongyloides hyperinfection with concurrent cytomegalovirus (CMV) infection and gram-negative sepsis from North India.

Case Report

A 59-year-old Indian female presented to our hospital, with c/o abdominal distension for last 2 months, generalized weakness, productive cough, and purpuric rashes over both lower limbs and fever for 2 days. The patient was a known hypertensive and hypothyroid on medications and past history of cholecystectomy 17 years back.

She was recently diagnosed as a case of chronic liver disease due to autoimmune hepatitis 3 months back was being treated for the same. She was started on wysolone 60 mg for last 3 months and azoran 100 mg for past 1 month.

On general examination, she was conscious, oriented, and afebrile. Physical examination revealed pallor, pedal edema, palpable purpuric spots on both the lower limbs. Her blood pressure was low (80/50 mm of Hg), progesterone receptor - 118/min, and risk ratio - 20/min. Chest examination revealed bilateral normal air entry with basal crepitations. Abdomen was distended and tender with sluggish bowel sounds.

Initial laboratory investigation confirmed anemia (hemoglobin - 9.3 g/dl), total lung capacity 8.9 × 109/L with neutrophilia, (neutrophil - 83%, lymphocyte - 11%, and eosinophil - 1%), and platelets 139 × 109/L.

Her kidney function were deranged - urea 120 mg/dl, creatinine 2.08 mg/dl, sodium 133 mmol/L, and potassium 4.39 mmol/L. Liver function tests were also deranged, (total bilirubin - 1.4 mg/dl, aspartate aminotransferase - 98 IU/L, alanine aminotransferase - 82 IU/L, serum alkaline phosphatase - 519 IU/L, gamma glutamyl transferase - 800 IU/L, albumin - 2.0 g/dl, and globulin - 3.3 g/dl).

Arterial blood gas revealed respiratory acidosis and lactate 3.2 (pH - 7.30, HCO3 - 20 mm Hg, PCO2 - 46 mm Hg, and PO2 -87 mm Hg.) C reactive protein 144 mg/L, because of the worsening respiratory status and altered sensorium she was intubated and put on a mechanical ventilator. She also had paralytic ileus (high RT aspirate 600 ml/24 h).

Chest X-ray showed bilateral fluffy alveolar opacities with infiltrates, left side consolidation and right homogenous opacities with ground glass appearance. Baseline ECHO with 50%, no regional wall motion abnormality, inferior vena cava 20. Ultrasonography showed liver with irregular outlines and coarse echotexture, minimal interloop ascites, few dilated fluid filled small bowel loops were seen with sluggish peristaltic movement.

Cytologic examination of the bronchial wash and lavage comprised benign respiratory epithelial cells, few polymorphs and histiocytes over hemorrhagic background. A wet mount was seen which revealed motile larvae resembling larvae of Strongyloides stercoralis [Figures 1–4].

Figure 1

Coiled up strongyloides larvae

Figure 4

Embryonated egg

Double bulb esophagus

Primordial genital primordium

Interestingly bronchoalveolar lavage culture grew Klebsiella pneumoniae. Other cultures were sterile. CMV DNA quant 1.81 × 106/ml.

Absolute eosinophil count was −55/cumm (reference range 40–440) Serum immunoglobulin E was 319 (reference range 100). Skin biopsy showed occasional thrombi in dermal vessels with extravasation of red blood cells; epidermis was largely unremarkable which is compatible with purpura fulminans. No larvae were seen.

Treatment

Antibiotics were added as per sensitivity reports. Ivermectin 12 mg once daily was added. A high ionotropic support was given to maintain mean arterial pressure of 65 mmHg.

Further course

She had a sudden onset of cardiac arrest and despite best possible effort. She could not be revived. Postmortem liver biopsy features were consistent with liver cirrhosis with features of sepsis. Muscle biopsy showed transversely and longitudinally cut muscle fibers with a focal group of atrophic muscles.

Discussion

Fatal S. stercoralis hyperinfection with immune suppression was first reported in 1966 by Cruz et al.[2] Immunosuppression may occur due to steroids and other immunosuppressants. Some viruses such as CMV, also lower immunity. Female worms produce more eggs in the presence of exogenous steroids; this further facilitates worm growth and development.[34] In our patient, all the above factors got together to deliver the fatal blow.

Hyperinfection may develop as early as 20 days after the onset of corticosteroid therapy and as late as several years in immunocompetent persons.[56] Symptoms may include dyspnea, cough, pleuritic chest pain, hemoptysis, infiltrates of varying character on chest imaging, and mild blood eosinophilia. Concomitant use of corticosteroids or bacterial coinfection, as seen in our patient, suppresses the eosinophilia. Respiratory failure may occur in severe cases.[7] Purpura fulminance has been described in both sepsis and strongyloidiasis. In Strongyloidiasis, it is periumbilical and thumbprinting in appearance. In such cases strongyloidiasis larvae is seen in the skin biopsy, this was absent in our case. Therefore, Purpura in our case could be due to underlying sepsis. Strongyloid larvae carry gastrointestinal flora, while it migrates, causing sepsis.[89]

Paralytic ileus, caused by obstruction resulting from heavy parasite burdens may be a subtle pointer.[10]

Ironically, an inverse relationship between autoimmune liver diseases and S. stercoralis infection, has been proposed, a possible link between deworming and the emergence of immunological disease has been described, with some authors suggesting helminths, safe and effective in the treatment of inflammatory bowel disease: A possible example of Th2 conditioning of the mucosal immune response.[1112]

However, a high mortality despite therapy warrants, not only screening and monitoring but, a state of constant, high alert as concurrent sepsis may further obscure the presentation and waylays the clinician.

As stool studies are often negative, aspiration of duodenojejunal fluid and enzyme-linked immunosorbent assay serologic testing may be used as adjunct diagnostic tools.[13] Patients who have positive serologic tests and an exposure history, regardless of a negative stool results, should receive a course of treatment (ivermectin, 200 μg/kg/day for 2 days, and repeat after 2 weeks).[14]

Subsequent decisions about screening and prophylactic ivermectin must be individualized, but at the very least, a low threshold for performing stool exams should be maintained. Persons residing in strongyloidiasis-endemic areas or in high-risk occupations need to be educated about modes of parasite transmission to avoid recurrent infection.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.