Dermatologic Manifestations of the Immune Reconstitution Inflammatory Syndrome
Section snippets
Definition
IRIS can be defined as a pathologic inflammatory response to preexisting microbial, host, or other antigens that results in clinical deterioration in HIV-infected persons after initiating HAART. The suppression of HIV replication allowing gradual restoration of immune capacity is central to the pathogenesis of IRIS [5]. IRIS has also been referred to in the literature as “immune restoration disease” and “immune reconstitution syndrome.”
Shelburne and colleagues [6], [7] have proposed the
Dermatologic manifestations of immune reconstitution inflammatory syndrome
A reduction in the incidence of many HIV-related skin conditions has been documented in the HAART era, and many skin conditions present before commencement of HAART improve or resolve with HAART [43], [44], [45], [46]. Nonetheless, IRIS has manifested with a range of skin conditions, both infective and noninfective. There may be associated systemic IRIS manifestations. In reporting cases of dermatologic IRIS in the literature, some authors have used a strict definition to define IRIS, such as
Herpes simplex virus type 1 and 2
Several case series have reported a clustering of herpes simplex episodes after the initiation of HAART, mostly anogenital [14] and some particularly severe [7], [47]. Whether HSV occurs with increased frequency after HAART is not established. In some series any case of HSV occurring after HAART is initiated is regarded as an IRIS event [14], [31], [32]. Ratnam and colleagues [30], however, were more strict in their definition: “herpes simplex virus infection, recurrent disease was defined as
Molluscum contagiosum
Mollusca are common and self-limited in immunocompetent young adults and children, but in immunocompromised patients they tend to be more widespread and persistent [111]. Molluscum lesions may respond to HAART [46], [112], [113]. In one study of a cohort of 199 patients, however, four developed molluscum contagiosum as an IRIS phenomenon. The lesions occurred a median of 8 weeks after starting HAART [30]. There are also case reports of IRIS presenting as inflamed mollusca [14], [31]. A case of
Mycobacterium avium complex
MAC IRIS is commonly described and typically presents with focal adenitis or pulmonary lesions, unlike the disseminated disease that is seen in patients not receiving HAART [5], [67]. When MAC occurs as an IRIS phenomenon, caseous granulomas are seen. This presentation is unusual in patients not receiving HAART [5]. Cutaneous IRIS manifestations have been described in six patients, usually in association with other manifestations. Other cases resembling IRIS were described in the era of
Cryptococcosis
Nondermatologic manifestations of cryptococcal IRIS are described frequently. The most common is the recurrence of meningitis in patients who have a history of previous cryptococcal meningitis and who are receiving appropriate antifungal therapy when they start HAART [16], [17], [18], [19]. Deaths related to this recurrence have been reported [16], [19].
There are four case reports of IRIS presenting as cutaneous cryptococcosis. The first two patients had been treated recently for cryptococcal
Leishmaniasis
In endemic areas, leishmaniasis is an HIV-associated OI [118]. Posada-Vergara and colleagues [88] reported two cases of cutaneous leishmaniasis presenting as IRIS. One of the patients presented 1 month after starting HAART with a genital ulcer and papules and erythemato-violaceous plaques on his arms. Three months later the lesions worsened, with ulcer formation on the oral and nasal mucosa and infiltrative macules and papules developing on his face. There was associated odynophagia. Serologic
Sarcoidosis
HIV and sarcoid coexist relatively infrequently, perhaps because of the inability of the depleted CD4 cells to stimulate macrophages and mount the immune response required to form granulomas and manifest with sarcoid. Improvement of sarcoidosis with progressive HIV-related immunosuppression also has been described [122], [123], [124]. It is not surprising, then, that sarcoid is one of the conditions associated with immune restoration during HAART [7], [8], [23], [24], [25], [26], [27], [28],
Lupus erythematosus presenting as immune reconstitution inflammatory syndrome
It has been suggested that the immunosuppression of HIV prevents systemic lupus erythematosus (SLE); thus fewer than expected cases of SLE are reported in HIV-infected patients [93]. Improvement in SLE clinical manifestations that paralleled progressive immunodeficiency in HIV has been noted [125]. It would be expected that, as immunity improves with HAART, those susceptible to SLE would manifest clinically [126].
Diri and colleagues [93] reported a patient who developed SLE manifesting with
Summary
This article has reviewed the spectrum of dermatologic manifestations of IRIS. Dermatologic IRIS accounted for roughly half of IRIS cases in several series. The commonly described manifestations are in relation to HZV and HSV. Although most dermatologic IRIS manifestations cause moderate symptoms and respond to conventional therapy for the associated condition, certain cases may be complicated, refractory to conventional therapy, or even life threatening. Indeed fatal cases of visceral KS IRIS
References (130)
- et al.
Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies
Lancet
(2002) - et al.
Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals
Lancet Infect Dis
(2005) Paradoxical responses during the chemotherapy of tuberculosis
J Infect
(1987)- et al.
Sarcoidosis in a patient with AIDS: a manifestation of immune restoration syndrome
J Am Acad Dermatol
(1999) - et al.
Recurrent pulmonary sarcoidosis in HIV-infected patients receiving highly active antiretroviral therapy
Chest
(2001) - et al.
Herpes zoster as an immune reconstitution disease after initiation of combination antiretroviral therapy in patients with human immunodeficiency virus type-1 infection
Am J Med
(2001) - et al.
Varicella zoster as a manifestation of immune restoration disease in HIV-infected children
J Allergy Clin Immunol
(2004) - et al.
Effect of highly active antiretroviral therapy on frequency of oral warts
Lancet
(2001) - et al.
Changing prevalence of oral manifestations of human immuno-deficiency virus in the era of protease inhibitor therapy
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
(2000) - et al.
Unusual manifestations of disseminated Histoplasmosis in patients responding to antiretroviral therapy
Am J Med
(2005)