A case of fulminant varicella infection with purpura fulminans, hepatitis, and rhabdomyolysis.

Varicella zoster virus causes varicella which is a common disease. Generally it is self-limiting, and treatment is often unnecessary, but severe or life-threatening complications are rarely seen. We report a case of fulminant varicella complicating with purpura fulminans, hepatitis, and probable rhabdomyolysis in a previously healthy child.

What was known?

1. Varicella zoster virus (VZV) infection is frequent, highly contagious and rarely causes complication in children.

2. Immunosuppressed patients are at greater risk of VZV complications.

Introduction

Varicella zoster virus (VZV) infection is prevalent in children. It is highly contagious, and spreads by close contact with an infected person.[1] While starting antiviral therapy in the early stage of the disease is useful in preventing complications it seems that the most useful approach is to prevent infection by vaccinating children at an early age.[2]

We present a previously healthy child suffering from chicken pox with purpura fulminans, hepatitis, and probable rhabdomyolysis.

Case Report

A 4.5-year-old unconscious boy was admitted to hospital with diagnosis of disseminated varicella infection, sepsis, and secondary staphylococci infection, and he was transferred to the intensive care unit because of loss of consciousness. Since spontaneous respiration was weak he was intubated and required mechanical ventilatory support till his death. Ten days before admission he had a history of otherwise uncomplicated mild chicken pox together with three of his siblings. He had been treated with antipyretics and antipruritic lotions but not acyclovir. There was no vesicular eruption. Three days before hospitalization swelling and bluish discoloration developed on his right forearm and 2 days later it ulcerated [Figure 1].

Figure 1

Excoriated papules with serohemorrhagic crusts over the child's face, and extremities. On the right forearm a sharply bordered plaque with hemorrhagic necrotic crusts was present

Physical examination revealed high-grade fever, hypotension, and severe dehydration. Lungs were clear to auscultation bilaterally. There was hepatomegaly and abnormal bilateral extensor plantar response was elicited. There was no neck stiffness. On dermatologic examination excoriated papules with serohemorrhagic crusts 1-3 mm in size scattered over his face, trunk, and extremities were noted. On the flexor surface of the right forearm a sharply bordered plaque with hemorrhagic necrotic crust and deep ulceration was present. His past medical history was unremarkable.

On laboratory tests coagulation screening revealed high d-Dimer (30 ng/ml; cut-off, <0.5 ng/ml), fibrinogen (465 mg/dl; normal level (nl), 200-400 mg/dl) levels and prolonged activated partial thromboplastin time (41.6 seconds; nl: 25-40), protrombine time (55 seconds; nl: 70) and they remained unchanged in following days. The complete blood count showed elevation of white blood cells (first day: 9200/mm3, second day: 17 000/mm3; nl: 4000-11000/mm3) and thrombocytopenia (first day: 133000/mm3, second day: 94 000/mm3; nl: 150-400 000/mm3).

Alanine aminotransferase (first day: 324 U/l, second day: 479; nl, N: 0-41 U/l) and aspartate aminotransferase (first day: 1402 U/l, second day: 1082; nl, N:0-37 U/l) were high and kept rising later. On second day creatine kinase (CK) (35981 U/l; nl, 38-174 U/l), CK-MB (1227 U/l; nl, 0-24 U/l), lactate dehydrogenase (LDH) (5372 U/l; nl, 340-480 U/l), sedimantation (42 mm/h; nl, 1-20 mm/h), and C-reactive protein (238 mg/l; nl, 0-5 mg/l) were high. On urinalysis there were 5 erythrocyte, 7 leukocyte, and 200 mg/dl protein (normal; 0-4 erythrocytes, 0-4 leukocytes, and negative protein). VZV immunglobuline M was positive. TORCH panel, hepatitis markers (HbsAg, anti HCV), and anti-HIV are negative.

The patient was diagnosed as having varicella complicating with purpura fulminans, hepatitis, and probable rhabdomyolysis. The patient was monitorized and intubated. He was started on vancomycin (60 mg/kg, four times a day), cefotaxime (200 mg/kg, three times a day), and acyclovir (15 mg/kg three times a day) treatment. Topical silver sulfadiazine cream was applied two times a day on arm lesions.

Unfortunately, he died in the morning of 4th day after admission. Hemorrhagic necrotic ulcerative plaque did neither expand nor did spread to other parts of body.

Discussion

Varicella rarely causes complications, but it is not always harmless mostly in adolescents, adults, and immunosuppressed people. Though in adults, the complication rate of varicella infection is several fold higher and tends to be disastrous for the affected patient,[3] our previously healthy patient was 4.5 years old and there was no predisposing factor to explain VZV dissemination.

Hospitalization rates for varicella are about 3-6 per 1000 cases and complication ranges between 2% and 4%. Mortality rates are between 0 and 0.05 deaths/100,000 population per year in Europe.[4] In a study conducted by Rivest et al.,[3] the reported complication rate was 29.2 cases/10,000 cases of varicella and 0.82 cases/100,000 children/year by Cameron et al.,[5] including necrotizing fasciitis and other skin infections, pneumonia, bacteriemia, encephalitis, ataxia, aseptic meningitis, Guillain-Baré syndrome, hepatitis, thrombocytopenia, dehydrations, febrile convulsions, antihistamine intoxication, congenital varicella, DIC, stomatitis, synovitis, purpura fulminans, empyema with bacteriemia, and death.

Purpura fulminans (PF) results in microvascular thrombosis together with hemorrhagic skin and soft tissue necrosis. It is classically defined by purpuric skin lesions, fever, hypotension, and DIC. Three forms of PF are defined: (1) neonatal purpura fulminans is associated with a hereditary deficiency of the natural anticoagulants such as protein C and S, (2) idiopathic or chronic purpura fulminans occurs after a latent period in a viral illness, and (3) in the setting of superimposition of a bacterial infection acute infectious purpura fulminans occurs.[6] We diagnosed our patient as having purpura fulminans with the presence of fever, hypotension, and hemorhhagic necrotic skin lesions.

Rhabdomyolysis is caused by a variety of disorders, alcohol, and other drug-related toxication, muscle compression, and trauma (Crush syndrome) being among commonest ones. Others are inflammatory, autoimmune, and metabolic muscle diseases, ischemia and viral infections. There are also a lot of case reports of rhabdomyolysis complicating VZV infections.[78] Elevated creatine kinase is the most sensitive indicator of muscle injury and was elevated in our case.[8] Also AST and LDH levels were elevated which may be secondary to rhabdomyolysis. Unfortunately we did not perform tests for myoglobinemia and myoglobunuria. All these findings suggest varicella-induced rhabdomyolysis.

Immunosuppressed patients are at greater risk of VZV pneumonia, hepatitis, meningitis, and disseminated varicella. If possible patients should be vaccinated prior to immunosuppresive treatment to prevent primary VZV infection. In the case of infection immunosuppressive treatment should be discontiuned and i.v. acyclovir treatment should be started. Combination with IVIG treatment is reported to be life saving.[910]

Varicella vaccines contain live-attenuated Oka strain of VZV. It is contraindicated in people with history of severe reaction to the vaccine or its components, in pregnant women, in people with HIV, hematologic, and solid tumors, congenital immunodeficiency, and long-term immunosuppressive therapy. Several studies have showed that varicella vaccination significantly lowered hospitalization rates, ambulatory visits, varicella-related deaths, and expenditures and has resulted in a substantial decline of severe disease. When compared to one-dose immunization two injections of varicella vaccine provide a greater degree of protection.[2811]

Conclusion

In conclusion vaccination and early treatment might have prevented disseminated varicella. We must keep in mind that varicella may follow a fatal course in previously healthy children.[12] May be it is time to make varicella vaccination routine for all infants to prevent devastating sequelae of varicella infection as in our patient.

What is new?

1. Varicella may follow a fatal course in previously healthy children.

2. Varicella vaccination routine for all infants to prevent devastating sequelae.