Severe varicella infection occurring after herpes zoster reactivation in a patient with AIDS

Abstract

Herpes zoster reactivation occurs in patients who had primary varicella infection, afflicting mainly the elderly and the immunocompromised. However, it is rare that varicella infection develop after zoster reactivation. We report on a patient with underlying HIV/AIDS who had two previous episodes of herpes zoster and still developed varicella infection, complicated by pneumonitis and polyradiculitis. We also review the relevant literature.

BACKGROUND

Varicella zoster virus (VZV) causes primary varicella infection, manifesting as a vesicular rash and occasionally causing complications such as pneumonitis and neurological infections in adults and immunocompromised hosts. The virus then lies dormant and may reactivate in the elderly or in immunocompromised states, causing herpes zoster, which can disseminate. Disseminated zoster, defined as having more than 20 vesicles outside the area of primary and adjacent dermatome, may involve visceral organs.¹

Virological diagnosis to ascertain recurrence or reactivation of varicella is often difficult, due to lack of sensitivity of the virus culture. However, with the advent of polymerase chain reaction (PCR), the diagnosis of VZV can be made more easily and with greater certainty.

Reactivation of varicella infection has been reported in patients with underlying haematological malignancies^2,3 and in two HIV patients in the English literature.^4,5 However, these two HIV patients did not have prior zoster on presentation. Fraisse et al reported a patient with AIDS who had two episodes of VZV pneumonitis treated with a month of acyclovir each time and subsequently required maintenance acyclovir.⁴ Acheson reported another patient who possibly had four episodes of varicella infection, with no definite episode of zoster, or chronic varicella infection, given the short time lapse between each reactivation. The patient was refractory to acyclovir and had to be treated with varicella zoster immunoglobulin, as there was possibility of acyclovir resistance.⁵ It is, however, rare that the virus can cause varicella infection again after herpes zoster—that is, without dermatomal involvement—and to our knowledge, none has been reported in the English literature.

We report a case of severe varicella infection in a patient with underlying HIV/AIDS who had a history of zoster. This was complicated by pneumonitis and polyradiculitis which improved with acyclovir treatment. The infection was eventually confirmed by a positive VZV PCR from the cerebral spinal fluid.

CASE PRESENTATION

A 52-year-old Chinese man with a history of β-thalassaemia trait was first diagnosed with HIV/AIDS in June 2007 when he presented with dyspnoea and confirmed to have Pneumocystis jiroveci pneumonia (PCP). His absolute CD4 count then was 42 cells/μl. He had a positive cytomegalovirus (CMV) IgG but other baseline serologies were negative for hepatitis B and C, syphilis and toxoplasma. After completing treatment, he was initiated on antiretroviral therapy (ART) but defaulted the subsequent follow-up after a month. He presented a year later in June 2008 with a second episode of PCP and was incidentally found to have pulmonary mycobacterium avium complex (MAC). His absolute CD4 had further declined to 9 cells/μl (1%) without ART. He was commenced on treatment for both PCP and MAC. His other significant past medical history included recurrent herpes zoster infection; the first episode in 2007 involved the right C2/3 dermatome and left T7 dermatome, and the second episode involved the ophthalmic branch of the left trigeminal nerve in March 2008. He presented in July 2008 with a 2 day history of generalised polymorphic vesicular rash, and complained of difficulty walking. He denied dyspnoea and there were no urinary or bowel symptoms.

Physical examination revealed a crop of vesicles, some of which had scabbed. There were hypopigmented scars from his previous zoster infections (figs 1 and 2). Respiratory examination revealed bilateral lung crackles although oxygen saturation was 98% on room air. In addition, he was noted to have neurological findings consistent with bilateral symmetrical sensorimotor polyneuropathy of both his lower limbs, with loss of sensation distally from the knees. Romberg’s sign was positive, and his gait was broad based. The cranial nerve examination was otherwise normal, the neck was supple, and there were no cerebellar signs.

Figure 1.

(A) Hypopigmented scars from zoster of the ophthalmic division of the left trigeminal nerve. (B) Zoster scar of the right C2/3 dermatome.

Figure 2.

(A) Varicella polymorphic vesicular rash on the trunk. (B) Hypopigmented scar of previous left T4 dermatome zoster (red arrow) on a background of scabbed haemorrhagic varicella vesicles.

INVESTIGATIONS

Laboratory investigations were significant only for a C reactive protein of 71 mg/l (normal range (NR) 0 – 6 mg/l) and white cell count was 3.7×10⁹/ml (NR 3.6–9.3×10⁹). There was no disseminated intravascular coagulopathy (DIC) and liver function tests and creatinine were normal. The chest radiograph showed florid bilateral infiltrates (fig 3).

Figure 3.

Chest radiograph showing bilateral pulmonary infiltrates, consistent with pneumonitis.

Lumbar puncture was performed after an unremarkable computer tomogram of the brain and a normal magnetic resonance imaging of the lumbar sacral spine. Opening pressure was 8 cm H₂O and cerebrospinal fluid (CSF) investigations revealed a white cell count <1 cell/μl, predominantly lymphocytes after centrifuge, and red cells of 866c ells/μl. Total protein was raised at 1.35 g/l (NR 0.1–0.4 g/l), but glucose was normal at 4.3 mmol/l (NR 2.5–5.5 mmol/l). CSF cryptococcus antigen and herpes simplex DNA were negative. CSF cultures had no growth. Nerve conduction study and electromyogram revealed polyradiculitis consistent with an infection.

TREATMENT

The initial assessment was severe varicella infection with pneumonitis and possible acute inflammatory demyelinating polyneuropathy for which he was promptly commenced on intravenous acyclovir at 10 mg/kg every 8 h.

OUTCOME AND FOLLOW-UP

The patient developed transient type 1 respiratory failure a day after admission and he was started on intravenous piperacillin–tazobactam in addition to acyclovir. His respiratory status improved after 4 days and piperacillin–tazobactam was stopped when blood cultures did not yield any bacterial growth. He made a good neurological recovery after completing 10 days of intravenous acyclovir. An eye examination was normal and did not reveal any signs of acute retinal necrosis. VZV immunofluorescence and viral culture of skin vesicles were negative. Our diagnosis of VZV infection was eventually confirmed when the spinal fluid VZV PCR returned positive. The patient was subsequently discharged, and planned to resume ART in the outpatient setting. He was well and did not have any recurrence of vesicular rash at 1 month of follow-up.

DISCUSSION

We describe a rare case of chickenpox (akin to primary varicella infection) in a patient who already had two episodes of herpes zoster as evident from his history and physical examination. The criterion of disseminated zoster was not met as there was no dermatomal distribution of the rash in addition to the generalised cutaneous vesicles that he had. Although the virus was not cultured or identified via immunofluorescence, his rash was characteristic of varicella infection. This may have been due to crusting of most cutaneous vesicles at the time of presentation or poor sampling technique. The positive VZV PCR in the CSF, however, confirms that our patient did have disseminated varicella infection, with respiratory and neurological involvement, to which he responded to a 10 day course of treatment with intravenous acyclovir.

Infection with varicella zoster is a frequent opportunistic occurrence in adults with HIV. Serious complications such as hemorrhagic varicella, pneumonitis and neurological involvement such as encephalitis, meningitis and polyneuritis are more common than healthy individuals. Up to 89% of HIV patients have a positive VZV IgG, indicating past infections,⁶ thus putting them at risk of developing zoster and other varicella related complications when their immunity declines.

In conclusion, our case demonstrates that varicella infection can occur in individuals after zoster reactivation, especially in patients with HIV/AIDS. Varicella zoster complications commonly afflict the immunocompromised and should be treated promptly with intravenous acyclovir.

LEARNING POINTS

• Varicella infection can occur after zoster in immunocompromised patients, especially in persons with advanced HIV.

• Complications from varicella infection, such as pneumonitis and neurological involvement, tend to occur in immunocompromised hosts.

• Prompt initiation with acyclovir is crucial in patients with complicated varicella infection.