Introduction
Malaria, is the second largest killer of humanity after tuberculosis in tropical countries. Despite its common occurrence, it can sometimes befool the most astute of physicians. This is especially true of plasmodium falciparum infections, which if unrecognised may have a fulminant course with disastrous consequences.
Acute urticaria is a dermal reaction pattern represented characteristically by itchy wheals and is often associated with oedema of subcutaneous tissue called angioedema. Malaria very rarely has cutaneous manifestations except the ‘ominous’ purpura fulminans seen in severe plasmodium falciparum infections [1]. We report an unusual case of vivax malaria presenting with acute urticaria and angioedema.
Case report
A 21 year old serving soldier was admitted with multiple itchy wheals over body, swelling of lips and periorbital skin of one week duration. He developed episodes of pain abdomen followed by vomiting, dizziness, breathlessness. There was no history of fever, loose stools, wheeze, arthralgia, insect bite, consumption of incriminating food or drugs prior to onset of symptoms. On examination the patient had fever (temperature - 101.8°F), tachycardia (pulse - 108 per minute, regular) and postural hypotension (supine and sitting blood pressure of 118/80 and 88/56 mm Hg respectively). There was no pallor, icterus, cyanosis or lymphadenopathy. Systemic examination did not reveal any abnormality. Dermatological examination showed multiple geographic wheals on trunk, face and extremities. There was perioral and periorbital angioedema. Dermographism and Darier's sign were negative.
On investigation patient had haemoglobin of 11.2 g/dl, total leucocyte count of 8,600/ mm3, differential leucocyte count of polymorphs 70%, lymphocytes 24%, monocytes 1%, eosinophils 5% and erythrocyte sedimentation rate of 20 mm fall at the end of 1st hour. All other investigations including liver and renal function tests, stool routine examination, blood electrolyte levels, radiograph of chest and enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) were negative.
He was initially treated as a case of acute urticaria and angioedema with injectable and oral corticosteroids, inj ranitidine, antipyretics and oral antihistaminics with no relief of symptoms. Review of his clinical chart showed an alternate day pattern of rise of fever with the simultaneous appearance of urticarial wheals and angioedema and this raised the suspicion of malaria. A peripheral blood smear was done which was positive for ring forms of plasmodium vivax. Oral chloroquine was started and the patient showed a dramatic improvement in his condition with both fever and the urticarial rash subsiding within three days of starting the antimalarial treatment. Later radical therapy with primaquine was given. The patient was discharged after he had been symptom free for a week. An epidemiological investigation of the case was conducted by Officer Commanding, Station Health Organisation which included mass blood survey around the index case (75 slides), however no other case was found. Preventive focal pyrethrum and malathion spraying of accommodation was nevertheless carried out.
Discussion
Malaria is a febrile illness caused by protozoa of plasmodium species which is transmitted by bite of infected anopheles mosquito. It affects more than 1 billion people in 103 countries around the globe and accounts for 1-3 million deaths yearly [2].
The pathogenesis of acute urticaria is antigen induced, IgE mediated or direct mast cell degranulation. Degranulation of mast cells releases a constellation of mediators that are responsible for the various symptoms [3]. Acute urticaria though distressing is not life threatening unless accompanied with angioedema. Bronchospasm, abdominal pain, postural hypotension and syncope indicate massive mast cell degranulation.
A variety of infections including viral (Hepatitis B, Ebstein Barr Virus etc.), bacterial (Streptococci, Helicobacter etc.), fungal and protozoal have been implicated as triggers of acute urticaria [4]. Classically malaria, is not associated with skin rash, petechial haemorrhages in skin and mucous membrane but they occur rarely in falciparum malaria. A few case reports, from India cite instances of Plasmodium vivax malaria presenting with acute urticaria [5, 6].
The pathogenesis of acute urticaria in patients suffering from vivax malaria remains speculative. Plasmodial sporozoites inoculated while taking a blood meal, multiply in the liver producing daughter merozoites, which after release into the bloodstream, attach themselves to specific receptors on erythrocytes. This attachment is known to make the erythrocytes antigenic by altering red cell membrane, exposing the hitherto hidden surface antigen and inserting new parasite derived proteins [7].
The increased antigenicity of RBCs caused by plasmodial infection [7], or plasmodial antigens per se may be responsible for the massive mast cell degranulation in the present case. Whether this was mediated by immunological or direct mechanisms is unknown.
Conflicts of Interest
None identified
References
- 1.Keri JE, Thomas K, Berman B, Falabella A. Purpura fulminans in a patient with malaria. Eur J Dermatol. 2000;10:617–619. [PubMed] [Google Scholar]
- 2.Kalra SP, Naithani N, Mehta SR, Rajat Kumar. Resistant Malaria: Current Concepts and Therapeutic Strategies. MJAFI. 2002:228–233. doi: 10.1016/S0377-1237(02)80136-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Kaplan AP. Urticaria and angioedema. In: Kaplan AP, editor. Allergy. 2nd ed. Saunders; Philadelphia: 1997. pp. 573–592. [Google Scholar]
- 4.Sackesen C, Sekerel BE, Orhan F, Kocabas CN, Tuncer A, Adalioglu G. The aetiology of different forms of urticaria in childhood. Pediatr Dermatol. 2004;21:102–108. doi: 10.1111/j.0736-8046.2004.21202.x. [DOI] [PubMed] [Google Scholar]
- 5.Mitra A. Malaria presenting with urticaria as the initial feature. Indian Pediatr. 1989;26:728. [PubMed] [Google Scholar]
- 6.Maheshwari N, Maheshwari V, Mobashir M. Plasmodium vivax malaria presenting with urticaria. Postgrad Med J. 1989;65:2667. doi: 10.1136/pgmj.65.762.266-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.McKenzie FE, Jeffery GM, Collins WE. Plasmodium vivax blood-stage dynamics. J Parasitol. 2002;88:521–535. doi: 10.1645/0022-3395(2002)088[0521:PVBSD]2.0.CO;2. [DOI] [PMC free article] [PubMed] [Google Scholar]