Hansen’s Disease with HIV: A Case of Immune Reconstitution Disease

Abstract

Immune reconstitution inflammatory syndrome (IRIS) is an acute symptomatic expression of a latent infection during the recovery of the immune system usually as a response to antiretroviral therapy (ART). Opportunistic infections can trigger IRIS. Hansen’s disease is an infection caused by Mycobacterium leprae (M. leprae). There have been a limited number of case reports reporting the presentation of the co-infection of HIV and M. leprae. We report an unique case of IRIS in a patient co-infected with HIV and M. leprae presenting as an exacerbation of his Hansen’s Disease where the patient’s skin lesions progressed from borderline tuberculoid to lepromatous leprosy following ART administration.

Introduction

Immune reconstitution inflammatory syndrome (IRIS) is an acute symptomatic expression of a latent infection during the recovery of the immune system, usually as a response to antiretroviral therapy (ART). This syndrome usually affects human immunodeficiency virus (HIV)- infected individuals at advanced stages of HIV disease (CD4 lymphocyte counts <200 cells/µL).¹ Clinical signs of inflammation appear mostly in association with opportunistic infection such as Mycobacterium tuberculosis(TB), cytomegalovirus and herpes infections when ART triggers a generalized immune activation during the transition phase of HIV viral load suppression and CD4 lymphocyte increase.^1,2 Hansen’s disease is an infection caused by Mycobacterium leprae. There have been a limited number of case reports reporting the presentation of the co-infection of HIV and M. leprae.³ We report a unique case of IRIS in a patient co-infected with HIV and M. leprae presenting as an exacerbation of Hansen’s Disease where the patient’s skin lesions progressed from borderline tuberculoid to lepromatous leprosy following ART administration.

Case Report

The patient is a 25-year-old Micronesian man with a history of Hansen’s disease and HIV co-infection who presented to our outpatient clinic with an one month history of worsening skin rash on his arms and torso. The patient was initially diagnosed with borderline tuberculoid leprosy 6 years prior and treated with clofazimine, rifampin and dapsone for 11months before he returned to Micronesia where he was lost to follow up. See Table for timeline of events. His skin lesions were griscent when he returned to Hawai‘i 3 years later and was diagnosed with HIV. He was started on an ART regimen of efavirenz, lamivudine, and zidovudine (CD4 lymphocyte count of 320 cells/µL). After 6 months of taking his antiretroviral medications the patient stopped his medications because of personal and financial reasons and returned back home to Micronesia. Upon return to Hawai‘i his CD4 progressively declined to 144 cells/µL. He was started on a protease inhibitor based antiretroviral medication regimen (due to the presence of the K103N mutation) of once daily tenofovir, emtricitabine, and atazanavir/ritonavir three months prior to his current presentation.

Table.

Timeline of Events

Variable	7/2000	6/2001–1/2004	1/2004	2004–2006	10/2006	1/2007	7/2007
Clinical Course	- Noted to have 2 hypopigmented le- sions over torso and upper extremities - 1 area of ery- thematous, raised plaque over the anterior torso - Enlarged nerves of bilateral greater auriculars - Negative Tinel’s and Phalen’s signs - First diagnosis of Hansen’s disease	- Lost to follow-up - Living in Miconesia - No therapy for Hansen’s Disease	- Returned to Honolulu - First diagnosis of HIV - No skin lesions - Treatment for Hansen’s Disease not continued	- Lost to follow-up - Living in Miconesia - No therapy for Hansen’s Disease - No therapy for HIV infection	- Returned to Honolulu - No skin lesions noted - Not on antiretrovi- ral medication	- 3 months after restarting ART, patient presented with numerous hypopigmented le- sions over the torso and extremities - Plaques and nodules over both forearms - Had decreased pinpoint sensation over the areas of hypopigmentation and nodules - No ulnar nerve enlargement	- 9 months after restarting ART, skin lesions improved - Neurologic status unchanged (decreased pinpoint sensation over the areas of hypopig- mentation and nodules)
Pathologic Course - Skin Biopsy	Tuberculoid Leprosy					Lepromatous Leprosy
CD4 count, cells/µL			320 cells/µL		144 cells/µL		266 cells/µL
HIV RNA viral load, copies / ml				Prior to leaving to Micronesia, HIV RNA viral load was undetectable	20,000 copies/ml		Undetectable
Treatment for Hansen’s Disease	Clofazimine, ri- fampin and dapsone for 11months					Dapsone, clofazimine and azithromycin	Dapsone, clofazi- mine and azithromy- cin continued
Treatment for HIV			Efavirenz, lamivudine, and zidovudine for 7 months		Tenofovir, emtric- itabine, and atazanavir/ritonavir started 1 month after CD4 count obtained (delay in initiating ART was secondary to problems securing health insurance)	Tenofovir, emtric- itabine, and atazanavir/ritonavir	Tenofovir, emtric- itabine, and atazanavir/ritonavir

On review of systems, the patient reported feeling overall well but complained of progressive skin rash over his arms and torso for the past month which he described as painless, non-pruritic white spots. He denied any fever, chills, numbness, tingling, or hair loss over the eyebrows or lashes. He also had not had any recent cough, abdominal pain, vomiting, diarrhea or dysuria. On physical exam, the patient was afebrile with normal vital signs and appeared comfortable. His head and neck were without any palpable lymph nodes or prominent pre-auricular nerves and his heart, lung and abdomen exam were within normal limits. His skin exam was remarkable for numerous 2–3cm hypopigmented macules scattered on his torso and bilateral upper and lower extremities in addition to a 3–4cm erythematous plaques over both anterior surfaces of the forearms (Figure). There was no ulnar nerve enlargement palpated but he did have decreased pinpoint sensation over the areas of hypopigmentation.

Figure.

Skin lesions noted on patient who is dually infected with HIV and Hansen’s Disease.

a) Multiple hypopigmented to erythematous macules with diminished sensation

b) Papular and nodular lesions of left forearm

c) Initial skin biopsy (2000) showing epithelioid granulomas of lymphocytes and nonspecific chronic inflammation consistent with tuberculoid leprosy

d) Skin biopsy (2007) from left forearm showing vacuolated macrophages (foam cells) with predominantly superficial perivascular distribution and numerous well-preserved acid fast bacilli in clumps consistent with lepromatous leprosy.

Given the new skin lesions found on exam, there was concern for reactivation of the patient’s M. leprae infection and he was referred to dermatology clinic in addition to infectious disease clinic. Skin biopsies of the lesions showed vacuolated macrophages (foam cells) with predominantly superficial perivascular distribution and numerous well-preserved acid fast bacilli in clumps consistent with lepromatous leprosy (Figure). The diagnosis of lepromatous leprosy was confirmed by the Hansen’s Disease Center in Louisiana. A regimen of dapsone, clofazimine and azithromycin was started. On follow-up 9 months later, the patient’s skin lesions were still present but improved. Patient’s laboratory findings showed an undetectable HIV viral load and a CD4 lymphocyte count of 266 cells/µL.

Discussion

The clinical presentation of Hansen’s disease is chiefly dependent upon the host response to the organism, where skin lesions and neuropathy are most common. Those with more robust cellular immunity tend to present with fewer skin lesions in a more asymmetric pattern and few to no bacilli on tissue smear. This has been referred to historically as tuberculoid leprosy. In contrast, lepromatous leprosy typically manifests as widespread skin lesions including nodules and plaques with more severe nerve involvement and is attributed to those with a less vigorous cellular immune response as noted in our case.⁴

Given the essential role of cellular immunity in the clinical course of M. leprae, it would reasonably follow that HIV-positive individuals would be at greater risk for progression of disease as is the case with tuberculosis (TB). Indeed, it has been well documented that TB patients with HIV suffer more reactivation as well as reinoculation TB.⁵ One of the proposed mechanisms is a relative decreased production of interferon by T1 lymphocytes in HIV-positive patients, which increases susceptibility to the Mycobacterium. Conversely, it has also been reported that TB infection appears to worsen HIV by increasing HIV replication. This has been proposed to occur secondary to a Mycobacterium-induced production of tumor necrosis factor, interleukin-1 and interleukin-6 by macrophages.⁵ Although there have been several case reports on HIV patients co-infected with leprosy, unlike TB, there has been no evidence to show that M. leprae infection is associated with worse outcomes as compared to non-HIV infected individuals.^5,6 Several studies have also documented no significant alteration in ratio of lepromatous to tuberculoid disease in HIV-positive versus negative patients.⁵ However, over the past few years, there have been more than 10 cases of documented leprosy presenting as IRIS.^5,6 Several possible underlying mechanisms of IRIS and Hansen’s Disease have been proposed by Ustianowski, et al. They propose that initiation of HAART allows recovery of the body’s own cellular immunity which leads to a usual presentation of leprosy that would otherwise be dormant.⁵ Alternatively, IRIS could possibly serve as a trigger for a more aggressive type I reaction to the Mycobacterium explaining the severe reactions seen as in our case.⁷ Our case is the first case where there was a documented change in skin lesion from borderline tuberculoid to lepromatous leprosy following ART administration.

In summary, IRIS can present as worsening of leprosy in co-infected patients. Leprosy may be “unmasked” in the context of IRIS and treating physicians, particularly in highly endemic areas for Hansen’s Disease, need to be cognizant to this possibility.