Steven-Jonhson Syndrome in a Patient With Dengue Infection in Peru: A Case Report

Abstract

Stevens-Johnson syndrome is an infrequent condition affecting the skin and mucous membranes, it involves cutaneous detachment with high mortality without adequate treatment. We present the case of a 40-year-old male with a history of epilepsy treated with valproic acid and lamotrigine, previously diagnosed with dengue. Evaluation showed erythematous blisters on skin and mucosa with bleeding and desquamation, covering 10% of the body surface. The patient progressed favorably with the medical care received. Stevens-Johnson syndrome should be studied in association with arboviral diseases.

Introduction

Stevens-Johnson syndrome (SJS) is a rare and severe disease, with an estimated incidence of 0.4 to 1.2 cases per million inhabitants per year. ¹ This syndrome primarily manifests as a reaction to drugs, characterized by the appearance of generalized skin rashes, vesiculobullous lesions on the skin and mucous membranes, and in severe cases, skin detachment. ² Among the main triggers are anticonvulsants, such as lamotrigine, phenobarbital, and carbamazepine, responsible for approximately one-third of all cases. Clinical presentation can occur in the first days after starting a new drug treatment, and even up to 8 weeks later. ³

It is crucial to identify etiological factors, especially in patients with suspected viral infections, despite the relatively low association of this syndrome with common medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen. This is of great importance because even widely used medications like pain relievers can have a significant impact on the quality of life.^4-6

Although less common, other triggering mechanisms for SJS are related to vaccination or viral infections, such as human immunodeficiency virus (HIV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV). However, the association with less-frequent pathogens, like cytomegalovirus or dengue, is exceptionally rare, with few cases reported to date. ¹ Owing to the infrequency of this condition and the difficulty in identifying the etiological agent, we present a case of SJS associated with a dengue infection.

Clinical Case

A 40-year-old male patient from Ica, a coastal city in Peru, with a medical history of epilepsy, has been on treatment with valproic acid and lamotrigine for the past 10 years. He denies alcohol, tobacco, or drug use. Five days before the consultation, the patient experienced “red spots” and had a fever of 39.2°C, leading to a diagnosis of dengue through a positive NS1 antigen test. New samples were sent to the national reference laboratory, which confirmed the case by positive IgM antibody test. Since the patient had no risk factors, he was advised for home treatment with hydration and paracetamol.

During the dengue episode, the patient experienced general discomfort, ocular itching, and vesiculobullous skin lesions on the face, chest, and lower limbs, accompanied by fever and respiratory difficulty. These nonpruritic lesions, upon touch, would detach and secrete a serous fluid.

The physical examination revealed a patient in fair general and nutritional condition, with vital signs showing a blood pressure of 110/70 mmHg, a heart rate of 90 beats per minute, a respiratory rate of 16 breaths per minute, and oxygen saturation of 96% with an inspired oxygen fraction (FiO2) of 0.21%. Skin examination revealed bullous lesions with erythema on the head, upper limbs, lower limbs, and chest, while mucous membranes displayed bloody features and desquamative lesions. These manifestations affected approximately 10% of the total body surface. The Nikolsky sign was positive. Based on this clinical examination, SJS was diagnosed, and complementary tests were requested (Table 1).

Table 1.

Laboratory Follow-Up in the First 13 Days of Hospitalization.

Tests	Day 1	Day 5	Day 10	Day 13
Hemoglobin	12.5 g/dL	13.3 g/dL	13 g/dL	12.3 g/dL
Hematocrit	37%	39.3%	37.9%	37.8%
MCV	90.4 fL	90.1fL	91.8fL	92.9 fL
MCH	31.5 pg	30.5 pg	32.4 pg	32.6 pg
MCHC	32.9 g/dL	33.8 g/dL	33.3 g/dL	32.6 g/dL
Platelets	239.000/uL	364.000/uL	248.000/uL	293.000/uL
Leukocytes	5.760/uL	6.290/uL	11.400/uL	8.990/uL
Neutrophil	52%	67.3%	%	72.7%
Procalcitonin	0.345%	0.327%	0.303%	0.253%
C-reactive protein	25.6 mg/dL	40.5 mg/dL	38.9 mg/dL	20.2 mg/dL

MCV: mean corpuscular volumen, MCH: mean corpuscular hemoglobin, MCHC: mean corpuscular hemoglobin concentration.

The patient was admitted to the intensive care unit, where a treatment plan was implemented, including a hyperproteic liquid diet, hydration, dexamethasone administration, dermatological care, pain management, and modification of anticonvulsant therapy.

Despite initially slow progress, the patient showed gradual improvement (Figure 1). After 6 days in the intensive care unit, he was transferred to the internal medicine department, where he continued with a modified diet and antibiotic treatment. The patient experienced a seizure episode that was successfully treated with diazepam. Finally, he was discharged after 14 days with appropriate instructions and follow-up care.

Figure 1.

Desquamative skin lesions on lower limbs at day 7.

Discussion

Toxicodermias represent adverse skin reactions caused by the administration of drugs, whether topically, orally, or parenterally, affecting both the cutaneous tissue and mucous membranes. Various types of toxicodermias can arise, including exanthema, erythroderma, urticaria-angioedema, acneiform eruptions, SJS/Toxic Epidermal Necrolysis (TEN), hypersensitivity reactions, and photosensitivity.^7,8

The differentiation between SJS and TEN primarily lies in the extent of the lesions. Usually, when skin desquamation affects less than 10% of the total body surface, it is diagnosed as SJS; when it covers between 10% and 30%, the terms SJS and TEN overlap, and when it exceeds 30%, it is considered TEN. ⁸ Approximately 80% of SJS cases are related to medications, involving more than 200 drugs, while the remaining cases are attributed to infectious causes. ¹ Anticonvulsants, antibiotics, NSAIDs, and allopurinol are among the medications most frequently associated with this adverse reaction. In addition, certain diuretics such as amiloride, methychlothiazide, and metolazone have been linked to SJS. ⁵ The underlying pathophysiology involves an immunomediated hypersensitivity type IV response, leading to keratinocyte apoptosis. ³ Steven-Jonhson syndrome can occur up to 8 weeks after starting a medication. In our patient’s case, he had been taking anticonvulsants for 10 years, making it less likely that they were the cause of the SJS.

Considering the presented aspects, it is postulated that paracetamol could have been the causative agent in this case because clinical symptoms emerged 5 days after dengue treatment, with no apparent connection to other triggering factors.^9,10 Normal hematological analyses and negative blood cultures allowed for the exclusion of infectious processes. However, the reporting of other cases of SJS associated with dengue may suggest dengue as a triggering agent, for which more reports in scientific literature are needed. The patient’s recovery was satisfactory, including the discontinuation of paracetamol.

The significance of this case lies in the scarcity of reports of SJS associated with paracetamol in the scientific literature, as paracetamol is generally considered a safe drug. Moreover, it raises questions about the role of dengue as a potential triggering agent for SJS, as there have been reports of association, as well as with other mosquito-borne viruses such as Chikungunya. ⁸

Conclusion

This case emphasizes the importance of timely diagnosis and appropriate intervention in severe skin reactions such as SJS. Hospitalization, the withdrawal of suspect medications, life support measures, and constant monitoring are essential pillars in managing this potentially life-threatening condition. While it remains challenging to definitively establish Dengue as the sole cause, our findings indicate that paracetamol, another infrequently implicated agent, also plays a role. The intricate interplay of these potential infrequent origins, whether individually or in combination, adds significant value to this clinical case.