INTRODUCTION

Malaria is a major public health concern in Cameroon, with an entire population of over 22 million at risk of infection [1]. Severe malaria is a life-threatening form of the disease that may lead to organ dysfunction and death if not promptly treated. It is characterized by well-known clinical features, including pyrexia, severe anemia, impaired consciousness, and altered kidney function [2]. Cutaneous manifestations of malaria include petechiae, purpura, urticaria, and angioedema [3]. The occurrence of urticaria and angioedema is rarely listed as cutaneous manifestations of severe malaria and has not been detailly addressed in the literature. We present a case of severe malaria associated with urticaria.

CASE REPORT

A 34-year-old male presented to the emergency department with a four-day history of intermittent predominantly nocturnal fever and fatigue associated concomitantly with the onset of pruritic wheels on the face, including the lips and neck. The wheels were evanescent and migrated progressively to the trunk and arms. There was no swelling on the tongue, and he had no difficulties in breathing. He did not recall taking any medications, eating unusual meals, or using cosmetic products in the previous seven days. He was admitted at symptom onset in a health center, where he was given chlorpheniramine and dexamethasone for three days. The skin rashes reduced over these days. However, he was getting weaker, and his eyes gradually turned yellow and his urine dark brown. The onset of these new symptoms prompted his referral to our emergency unit for further investigation and treatment. He had no personal or family history of allergies, and his last diagnosis of malaria had been more than ten years back, treated on an outpatient basis with oral antimalarial and had lastly be dewormed three months earlier with oral albendazole.

On arrival at the emergency, his parameters were as follows: blood pressure = 108/64 mmHg, pulse = 108 bpm, respiratory rate = 26 bpm, SpO2 = 98% room air, and temperature = 38.2^oC. He was icteric and had discreet erythematous papules and plaques on his abdomen and arms (Fig. 1). The rest of the physical examination appeared to be within normal limits. Viral serologies for HIV and hepatitis B and C were negative. His workups are summarized in Table 1. Urine dipstick was positive for proteins = 3+, hemoglobin = 3+, ketones = 2+, and urine density = 1020. Abdominal ultrasound showed homogeneous hepatomegaly without biliary obstruction or stones.

Figure 1: Urticarial lesions on the arm appearing as discrete papules with an already fading erythema.

Table 1: Patient’s laboratory work-up.

A diagnosis of severe malaria was made, and he was treated with artesunate 192 mg every twelve hours for the first 24 hours and every 24 hours thereafter for four more days, followed by a relay with arterolane and piperaquine 150/750 mg combination for three additional days. He also received methylprednisolone 40 mg/day for 3 days and mequitazine 5 mg/day for 5 days.

His progress was marked by the complete regression of urticaria and fever by the second hospital day, jaundice, and dark urine by the fourth hospital day. By the fifth day, his malaria parasite load had reduced to zero prior to his discharge the following day.

DISCUSSION

This case highlighted a rare manifestation of one of the most common infectious diseases in sub-Saharan Africa. Urticaria and angioedema have been reported to occur in a number of parasitic infestations, including Cryptosporidiosis, Ascariasis, Strongyloidiasis, Echinococcosis, Giardiasis, and Trichinosis [4–6]. The occurrence of urticaria in malaria is not clinically distinguishable from an allergic reaction in the absence of the associated clinical and laboratory manifestations of malaria.

The occurrence of urticaria has been associated with Plasmodium falciparum and occasionally with Plasmodium vivax strains of the malaria parasite [7,8]. The underlying mechanism is poorly understood, and there is limited information on the topic. However, some hypotheses have been proposed. One of these hypotheses suggests that the deposition of malarial pigment in the reticuloendothelial system triggers the production of IgE antibodies that subsequently trigger urticaria. The presence of malarial pigment in the skin may activate the immune system and induce an allergic response, resulting in the release of histamine and other inflammatory mediators that cause urticarial rash [3]. Another hypothesis proposes that the immune response to the malarial infection itself may contribute to the development of urticaria. During infection with malaria, the immune system produces various cytokines and inflammatory mediators, which may lead to the activation of mast cells and the release of histamine, causing urticarial rash [9].

Although there are studies that have reported some genetic predispositions to the occurrence of severe forms of malaria [10], as well as in urticaria associated with other etiologies [11], there are no specific reports on the genetic predispositions to the specific occurrence of urticaria in malaria. Shama et al. reported an uncommon form of familial febrile urticaria due to malaria [9], suggesting the possibility of some genetic predispositions to the condition. Our patient had no family history of any form of urticaria, or allergies, and no genetic studies were performed to suggest any such genetic makeup.

The confirmatory diagnosis of malaria as the etiology of an acute febrile urticaria is based on the proof of the parasite invasion of red blood cells on microscopy [12]. This is crucial because a substantial proportion of febrile illnesses in malaria-endemic areas are not due to malaria infection [13]. Our patient had a very high parasite load (252,000 trophozoites/uL). However, there are no reports of any correlation between the parasite load and the occurrence of urticaria in severe malaria.

There is no consensus or guideline on how to approach the treatment of cases of malaria presenting with urticaria. In most similar case reports, corticosteroids and antihistamines were administered as adjuvants to specific therapy with antimalarials [3,7–9]. Since antihistamines and corticosteroids were used for symptomatic relief, only short-lived small doses were administered to our patient. The treatment of urticaria in this case was to alleviate the discomfort and itching. Drug choice was based on availability and side effect profile. Artemisinin derivatives and artemisinin-based combination therapy are the mainstay of treatment for malaria. They were used in our case following treatment guidelines [14]. The management of febrile urticaria in malaria should, thus, be individualized based on the patient’s clinical presentation, severity of symptoms, and response to treatment.

Close monitoring of the patient’s condition is essential to ensure appropriate management and to identify any potential complications. It is not known what peculiarity the occurrence of urticaria may have on the expected outcome of severe malaria. New-onset acute febrile urticaria should trigger investigations for malaria in individuals living in an malaria-endemic area or in people with a recent travel history to such an area.

CONCLUSION

Febrile urticaria may be the initial feature heralding the occurrence of severe malaria. A high level of suspicion should, thus, be maintained in people residing or travelling to malaria-endemic zones. New-onset febrile urticaria should trigger investigations for malaria in individuals at risk.

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