Editorial Comment: Flat Warts and the Immune Reconstitution Syndrome

The skin is the most common organ to manifest immune reconstitution syndrome (IRS).^1-3 While many viral dermatoses are described in the context of antiretroviral-induced immune recovery (eg, herpesvirus infections, molluscum, genital condylomata, verruca vulgaris),^4,5 the case report by Iarikov and colleagues⁶ is the first report of verruca plana in this setting. Cutaneous IRS is likely an underrecognized and underreported phenomenon. In our experience, and as illustrated by this case, the appearance of warts or molluscum during immune restoration often presents as the sudden onset of many lesions; alternatively, it may present as paradoxical enlargement or inflammation of preexisting lesions. While viral derma­toses may not be life-threatening, patients are often disturbed, disfigured, and stigmatized and have significant morbidity.

Misdiagnosing IRS as a medication reaction may lead to unnecessary interruptions in therapy. Eosino­philic folliculitis, which appears as pruritic, urticarial, follicular papules of the head, neck, and upper trunk, may be seen in the first 6 months of immune reconstitution and is often mistaken for a drug reaction. In fact, dermatological IRS including eosinophilic folliculitis can serve as a marker of a good virological response to antiretroviral treatment and should be recognized by the practitioner.

As most HIV clinicians are aware, diagnosing and defining IRS is problematic because there is no reliable biomarker. The case by Iarikov and colleagues illustrates this difficulty because it is not possible to conclude that their patient's flat warts did not represent a new human papillomavirus infection rather than unmasking of a preexisting infection. In our HIV dermatology clinic, we are frequently confronted with the conundrum of whether to interpret an event as IRS or simply as new or progressing disease occurring in the background of recovering, but still impaired, immunity. It is also difficult to know when and how aggressively to treat in this setting. Long-term observational studies are needed to determine whether disease-specific treatment in the setting of cutaneous IRS is necessary or effective. With the introduction of effective antiretroviral therapies in the developing world, where HIV infection is typically more advanced at diagnosis and IRS is probably more common, further characterization of IRS is becoming increasingly important.

Erin E. Huiras, MD
Fellow, International and HIV Dermatology
Department of Dermatology
University of California, San Francisco

Kieron S. Leslie, MBBS
Assistant Clinical Professor
Department of Dermatology
University of California, San Francisco
 

References 1. Ratnam I, Chiu C, Kandala NB, Easterbrook PJ. Incidence and risk factors for immune reconstitution inflammatory syndrome in an ethnically diverse HIV type 1-infected cohort. Clin Infect Dis. 2006;42:418-427.
2. French MA, Lenzo N, John M, et al. Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy. HIV Med. 2000;1:107-115.
3. Jevtovic DJ, Salemovic D, Ranin J, et al. The prevalence and risk of immune restoration disease in HIV-infected patients treated with highly active antiretroviral therapy. HIV Med. 2005;6:140-143.
4. Lehloenya R, Meintjes G. Dermatologic manifestations of the immune reconstitution inflammatory syndrome. Dermatol Clin. 2006;24:549-570, vii.
5. Huiras E, Preda V, Maurer T, Whitfield M. Cutaneous manifestations of immune reconstitution inflammatory syndrome. Curr Opinion HIV AIDS. 2008;3: 453-460.
6. Iarikov D, Duke W, Skiest D. Extensive development of flat warts as a cutaneous manifestation of immune reconstitution syndrome. AIDS Reader. 2008; 18:524-527.

No potential conflict of interest relevant to this commentary was reported by the authors.