Purtscher-like Retinopathy Related to Drug-induced Hypersensitivity Syndrome

Abstract

Purpose: To report a case with Purtscher-like retinopathy related to drug-induced hypersensitivity syndrome (DIHS).

Design: Case report. Methods: A 31-year-old male with fever, macula-papular rash, lymphadenopathy, and hepatitis was hospitalized.

Results: Eosinophilic leukocytosis, as well as cotton wool spots around the optic disc, was observed. Viral, bacteriologic, and parasitologic tests and rheumatologic markers were all negative. Given his history of antibiotic use, he was diagnosed as DIHS. On the seventh day he lost consciousness and and on the tenth day he died.

Conclusion: Purtscher-like retinopathy might be a sign of DIHS, and should be considered in the differential diagnosis where early intervention is needed.

KEYWORDS::

• DIHS
• Eosinophilia
• Fever
• Optic disc
• Retinopathy

Drug-induced hypersensitivity syndrome (DIHS) is a life-threatening systemic reaction characterized by rash, fever, hepatitis, lymphadenopathy, and leucocytosis with eosinophilia. It is triggered by a drug started 3 weeks to 3 months before symptom onset.¹ The most commonly implicated drugs include antiepileptic drugs, antibiotics, antivirals, dapsone, sulfasalazine, and allopurinol.² Purtscher-like retinopathy is a vaso-occlusive retinopathy associated with traumatic injury, acute pancreatitis, renal failure, and vasculitic diseases, such as dermatomyositis or lupus erythematosus.^3-5 Herein, we reported a case who presented with signs resembling Purtscher-like retinopathy.

CASE REPORT

A 31-year-old man presented with fever, rash, and blurred vision. He had no systemic illness or history of trauma. The only remarkable point in history was an antibiotic (amoxicilline plus clavulanic acid) prescription for flu 3 weeks earlier. He was free of fever and symptoms for 2 weeks.

His examination revealed macula-papular rash, lymphadenopathy, hepatitis, and eosinophilic leukocytosis. The patient was hospitalized. His complete blood count revealed 56,700 mm³ WBC, 61.7% eosinophil count (reference range 0.00–8.00%), and developed elevated transaminase levels (maximum alanine aminotransferase level, 5400 IU/L [reference range, 10.00–60.00 IU/L], and maximum aspartate aminotransferase level, 23,330 IU/L [reference range, 10.00–42.00 IU/L]). His total Ig E was 125.4 IU/mL (reference range 0.00–87.00). Markers for hepatitis B and C were negative. Ig M against cytomegalovirus, Epstein-Barr virus, human immunodeficiency virus (HIV), and herpes simplex virus types I and II were negative with enzyme-linked immunosorbant assay (ELISA). Culture of blood, pharynx, urine, feces, and parasitological examination of feces showed no infection.

On ophthalmologic examination his best-corrected visual acuity was 0.7, anterior segments were normal, and fundoscopic examinationrevealed cotton wool spots around the optic disc in both eyes (Figure 1a, b). Fundus fluorescein angiography showed hypofluorescence due to cotton wool spots. No signs of vasculitis were observed (Figure 1c, d).

FIGURE 1  (A-B) Fundoscopic examination revealed bilateral cotton wool spots around the optic disc. (C-D) Fundus fluorescein angiography revealed hypofluorescence due to cotton wool spots without any sign of vasculitis.

On the seventh day of his admission he had sudden loss of consciousness. Chest radiograph was normal. Cranial magnetic resonance imaging (MRI) and thorax and abdomen computed tomography (CT) revealed no pathology. To rule out meningitis and encephalitis, lumbar puncture was performed. Biochemical parameters were in normal range. Cerebrospinal fluid culture and Brucella agglutination tests were negative. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis and HSV were negative.

Bone marrow biopsy was done and culture for tuberculosis and leishmaniasis was negative. He had eosinophilia both in his peripheric blood and bone marrow. Real-time PCR for Faciola hepatica, Toxocara canis, hantavirus, Crimean-Congo hemorrhagic fever, and Toxoplasma were negative. His skin biopsy was compatible with hypereosinophilic syndrome. Specific serum respiration allergens like wheat pollens, cat, dog, and mold were negative with immunoblot test.

All viral, bacteriologic, and parasitologic tests and rheumatologic markers that could be examined were negative. Because he had a history of antibiotic use, he was diagnosed as DIHS. Prednisone 1 mg/kg was prescribed. A response to treatment and reduction of eosinophilia was observed. Unfortunately, the patient died 10 days after his admission because of progressive liver damage and fulminant hepatitis. He did not have any cardiac, pulmonary, or neurologic disease. The family denied forensic evaluation; thus, postmortem investigation was not possible.

DISCUSSION

We present a case with fever, maculopapular rash, lymphadenopathy, hepatitis, eosinophilic leukocytosis, and blurred vision. The only ophthalmologic finding was large cotton wool spots around optic disc. The fundus changes in our case resembled that of Purtscher-like retinopathy. However, the patient’s history did not include any traumatic injury or systemic diseases.

Drug-induced hypersensitivity syndrome is a rare and potentially fatal drug reaction. It has been most commonly associated with anticonvulsants, and 20% have been associated with antibiotics, including beta lactams. More than 70% of patients with DIHS have severe liver damage, which could lead to death.⁶

Differential diagnosis involved lymphoproliferative diseases, autoimmune diseases, vasculitis, infectious diseases, and allergic reaction to drugs like those used to treat serum sickness disease and drug-induced lupus. Our patient had no joint inflammation. Additionally, his skin biopsy as well as clinical and laboratory findings was not compatible with these diseases. Thus, we excluded these diseases.

Cotton wool spots may be detected in hypertensive retinopathy and diabetic retinopathy. They may be associated with a wide spectrum of diseases like AIDS, central and branch retinal vein occlusion, multiple myeloma, cardiac valvular disease, carotid artery obstruction, dermatomyositis, systemic lupus erythematosus, poliarteritis nodosa, leukemia, metastatic carcinoma, Purtscher retinopathy, and giant cell arteritis.⁷ Purtcher-like retinopathy shows the same clinical findings but is associated with other diseases, including pancreatitis, systemic collagen vascular diseases, chronic renal failure, and thrombotic thrombocytopenic purpura.⁸

To our knowledge, Purtcher-like retinopathy related to DIHS syndrome was not reported before and this might be a sign of DIHS. This finding also should be considered in the early diagnosis and treatment of this disease, which may lead to severe organ damage and death.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.