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Year : 2015  |  Volume : 60  |  Issue : 1  |  Page : 106
Immune reconstitution inflammatory syndrome unmasking erythema nodosum leprosum: A rare case report

Department of Dermatology, Venereology and Leprosy, Gandhi Medical College, Secunderabad, Andhra Pradesh, India

Date of Web Publication26-Dec-2014

Correspondence Address:
Geeta Kiran Arakkal
Department of Dermatology, Venereology and Leprosy, Gandhi Medical College, Secunderabad, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.147883

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Immune reconstitution inflammatory syndrome (IRIS) occurs as an acute symptomatic expression of a latent infection during the recovery of immune system in response to antiretroviral therapy in HIV patients. IRIS triggers both opportunistic and non-opportunistic infections. We report a case of IRIS in a patient with HIV, presenting as erythema nodosum leprosum (ENL), which led to unmasking of lepromatous leprosy following anti-retroviral therapy (ART).

Keywords: Erythema nodosum leprosum, Immune reconstitution inflammatory syndrome, lepromatous leprosy

How to cite this article:
Arakkal GK, Damarla SV, Chanda GM. Immune reconstitution inflammatory syndrome unmasking erythema nodosum leprosum: A rare case report. Indian J Dermatol 2015;60:106

How to cite this URL:
Arakkal GK, Damarla SV, Chanda GM. Immune reconstitution inflammatory syndrome unmasking erythema nodosum leprosum: A rare case report. Indian J Dermatol [serial online] 2015 [cited 2020 Sep 26];60:106. Available from: http://www.e-ijd.org/text.asp?2015/60/1/106/147883

What was known?
Immune inflammatory reconstitution syndrome (IRIS) commonly manifests as type 1 reaction in patients of HIV on anti-retroviral therapy (ART) when associated with leprosy.

   Introduction Top

In response to anti-retroviral therapy (ART), immune inflammatory reconstitution syndrome (IRIS) occurs as an acute symptomatic expression of a latent infection during the recovery of immune system in HIV patients. IRIS usually affects HIV-infected individuals at advanced stages of HIV disease (CD4 lymphocyte count <200 cells/mL). [1] Clinical signs of inflammation appear mostly in association with opportunistic infections such as Mycobacterium tuberculosis, cytomegalovirus and herpes infection etc., when ART triggers the generalized immune activation during the transition phase of HIV viral load suppression and an increase in CD4 lymphocyte. [1],[2] In the recent years, many cases were reported indicating interaction of HIV and Mycobacterium leprae with identification of IRIS after initiation of HAART in a patient with HIV and undetected leprosy.

   Case Report Top

A 38-year-old male, diagnosed as HIV-positive, presented to our department with multiple painful, erythematous skin lesions over extremities, face and abdomen of 2 days duration along with the history of evening rise of temperature with chills, malaise, body pains, joint pains, and ankle edema.The patient had history of nasal stuffiness and epistaxis. He was not a known case of leprosy. He was on ART zidovudine, lamivudine, nevirapine (ZLN) for 4 weeks prior to the onset of skin lesions. Further, history of sexual exposure with multiple heterosexual partners was noted. No history of diabetes mellitus, hypertension, or tuberculosis.

On general examination, he was pale, thin built, ill nourished and febrile. On examination, there was no generalized lymphadenopathy. There was diffuse infiltration of ear lobe [Figure 1]. Multiple erythematous, tender papules, and nodules were present on the face [Figure 2] and also on trunk and extremities [Figure 3]. Sensations of pain and touch were reduced over both the feet. Ulnar, radial cutaneous, lateral popliteal, and posterior tibial nerves on both sides were thickened and tender. Hair, nails and mucous membranes were normal. Systemic Examination revealed no abnormalities.
Figure 1: Diffuse infiltration of ear-lobe

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Figure 2: Multiple erythematous papules and nodules (ENL lesions) over face (a) and forehead (b)

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Figure 3: Multiple erythematous papules and nodules (ENL lesions) over lower limbs

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   Investigations Top

Hematological Examination revealed microcytic hypochromic anemia (Hb: 10 g%), and neutrophilic leukocytosis (TLC: 12,800/mm 3 ) differential count N 75 L 20 M 3 E 2 , and raised ESR (68 mm in-first hour). VDRL was non-reactive, and HBsAg was negative. The findings of complete urine examination were normal. Blood glucose levels, renal function and liver function tests were normal. Chest X-ray and ultrasonography of abdomen were normal. HIV-1 was reactive, the viral load was 1,07,400 copies/mL and CD4 count 94 cells/cu. mm before starting ART. At the time of diagnosis of IRIS, which is 1 month after starting of ART, CD4 count was 151 cells/cu. mm. Slit skin smear examination for M. leprae revealed bacteriological index of 4 along with a morphological index of 20%. Biopsy taken from the nodule on the left hand [Figure 3] demonstrated mild hyperkeratosis in epidermis, grenz zone. Dermis shows edema with collection of macrophages [Figure 4]. Vessels showed acute and chronic perivascular inflammatory infiltrate [Figure 5] consistent with ENL.
Figure 4: Low power view ×10. Mild hyperkeratosis in epidermis, grenz zone. Dermis shows edema with collection of macrophages

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Figure 5: High power view ×40.-Vessels show acute and chronic perivascular inflammatory infiltrate

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On the basis of the history, clinical examination, and investigative findings, a diagnosis of IRIS presenting as ENL in a patient of HIV with unmasking of lepromatous leprosy was made.

The patient was continued on ART and started on MBMDT (rifampicin:-600 mg, dapsone:- 100 mg, and clofazamine:-50 mg). He was given oral steroids which were gradually tapered over a period of 3 months. After 9 months of MBMDT and ART, no further episodes of ENL were reported and his CD4 count is 367. The patient is doing fine and attending to his duties.

   Discussion Top

IRIS is a clinical deterioration occurring as a direct consequence of rapid and dysregulated restoration of antigen immune response during highly active anti-retroviral therapy (HAART). [3]

IRIS describes a collection of inflammatory disorders associated with paradoxical worsening of pre-existing infectious process following the initiation of ART in HIV-infected individuals. [4]

According to the published description of the clinical manifestations of IRIS, the following case definition of IRIS in leprosy was suggested recently: [5] (1) leprosy/-leprosy type 1 reaction and ENL presenting within 6 months of starting ART, (2) advanced HIV infection, (3) low CD4 count before the start of ART, and (4) CD4 count increase after ART.

A low CD4 count before starting ART, advanced AIDS and prior opportunistic infections are considered to be potential risk factors for IRIS. [5] Although in leprosy patients type 1 reactions are more common, ENL was also reported rarely as IRIS. [6] We have diagnosed our case as IRIS presenting as ENL with unmasking as leprosy after satisfying above criteria.

Co-infection of leprosy and HIV has been well documented worldwide even if several aspects of this co-occurrence are not fully understood. Tuberculoid leprosy has high CMI at one end of the spectrum and has absent CMI in LL at the other end of the spectrum whereas HIV infection is associated with depressed CMI.

ENL is classically seen as an immune complex-mediated phenomenon initiated by the release of mycobacterial antigens, which leads to the formation of immune complexes and complement activation. [7] Newer data suggest that there is also increased T-cell activity in LL patients with ENL compared to those with LL-leprosy alone. The major T-cell subtype in ENL is the CD4 cell, in contrast to lepromatous leprosy where CD8 cells predominate. [8] The factors that determine the CD4 cell responses to ART are only partly known and depend on both the host and the virus. Considerable individual variation in the reconstitution of CD4cells has been noted. [9]

Early in the HIV epidemic there were fears that the immune suppression of HIV infection would worsen the leprosy outcome. Fortunately, this did not happen; instead, it is the immune reactivation after ART that dominates the clinical picture in patients with HIV and leprosy. [10] The initiation of ART allows the recovery of the body's own cellular immunity, which leads to presentation of leprosy that would otherwise be dormant. [10]

A literature search showed that only two cases of ENL occurring as IRIS was described till now. First case was presented at the International Leprosy Congress Hyderabad 2008 [11] and the second case was reported in British Medical Journal in 2009. [6]

We herewith report a case of IRIS in a HIV patient presenting as ENL with unmasking of lepromatous leprosy after 4 weeks of starting ART unlike Cusini et al., who reported IRIS after 13 months of ART. [6] Our observation shows that ENL may manifest as IRIS in HIV-infected patients as early as 4 weeks after initiation of ART depending on the type and degree of the immune recovery.

We observed that the line of management of ENL in the IRIS patient was not different from non-HIV patients with ENL and that the response to therapy of ENL in HIV patients is similar to that of non-HIV patients.

   References Top

Shelburne SA, Visnegarwala F, Darcourt J, Graviss EA, Giordano TP, White AC Jr, et al. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS 2005;19:399-406.  Back to cited text no. 1
Goebel FD. Immune reconstitution inflammatory syndrome (IRIS) - Another new disease entity following treatment initiation of HIV infection. Infection 2005;33:43-5.  Back to cited text no. 2
Dhasmana DJ, Dheda K, Ravn P, Wilkinson RJ, Meintjes G. Immune reconstitution inflammatory syndrome in HIV-infected patients receiving antiretroviral therapy: Pathogenesis, clinical manifestationsand management. Drugs 2008;68:191-208.  Back to cited text no. 3
DeSimone JA, Pomerantz RJ, Babinchak TJ. Inflammatory reactions in HIV-1-infected persons after initiation of highly active antiretroviral therapy.Ann Intern Med 2000;133:447-54.  Back to cited text no. 4
Deps PD, Lockwood DN. Leprosy occurring as immune reconstitution syndrome. Trans R Soc Trop Med Hyg 2008;102:966-8.  Back to cited text no. 5
Cusini A, Günthard HF, Weber R, Huber M, Kamarashev J, Bertisch B, et al. Lepromatous leprosy with erythema nodosumleprosum as immune reconstitution inflammatory syndrome in an HIV-1 infected patient after initiation of antiretroviral therapy. BMJ Case Rep 2009;2009.  Back to cited text no. 6
Kahawita IP, Lockwood DN. Towards understanding the pathology of erythema nodosumleprosum. Trans R Soc Trop Med Hyg 2008;102:329-37.  Back to cited text no. 7
Modlin RL, Gebhard JF, Taylor CR, Rea TH. In situ characterization of T lymphocyte subsets in the reactional states of leprosy.Clin Exp Immunol 1983;53:17-24.  Back to cited text no. 8
Battegay M, Nüesch R, Hirschel B, Kaufmann GR. Immunological recovery and antiretroviral therapy in HIV-1 infection. Lancet Infect Dis 2006;6:280-7.  Back to cited text no. 9
Ustianowski AP, Lawn SD, Lockwood DN. Interactions between HIV infection and leprosy: A paradox. Lancet Infect Dis 2006;6:350-60.  Back to cited text no. 10
Periche Fernandez J, Isa Isa R, Canario Lopez S, Velis Periche P. Erythema nodosumleprosum as immune reconstitution inflammatory syndrome in a HIV infected person. Int Lepr Congr 2008(abstr);71.  Back to cited text no. 11

What is new?
ENL manifesting as IRIS is being reported for its rarity. Line of management of ENL is similar in both HIV and non-HIV patients.


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]


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