Indian J Sex Transm Dis Indian J Sex Transm Dis
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Year : 2022  |  Volume : 43  |  Issue : 2  |  Page : 214-216

Severe beginning of the end (BOTE) sign in molluscum contagiosum after initiation of antiretroviral therapy in an AIDS patient: A possible immune reconstitution inflammatory syndrome manifestation!

1 Department of Dermatology, Venereology and Leprosy, GMCH, Chandigarh, India
2 Department of Pathology, GMCH, Chandigarh, India

Date of Submission21-Apr-2021
Date of Decision15-Mar-2022
Date of Acceptance25-Aug-2021
Date of Web Publication01-Aug-2022

Correspondence Address:
Dr. Ritu Mittal
Department of Dermatology, Venereology and Leprosy, GMCH, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijstd.ijstd_36_21

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How to cite this article:
Mittal R, Sandhu JK, Singh B. Severe beginning of the end (BOTE) sign in molluscum contagiosum after initiation of antiretroviral therapy in an AIDS patient: A possible immune reconstitution inflammatory syndrome manifestation!. Indian J Sex Transm Dis 2022;43:214-6

How to cite this URL:
Mittal R, Sandhu JK, Singh B. Severe beginning of the end (BOTE) sign in molluscum contagiosum after initiation of antiretroviral therapy in an AIDS patient: A possible immune reconstitution inflammatory syndrome manifestation!. Indian J Sex Transm Dis [serial online] 2022 [cited 2023 Nov 30];43:214-6. Available from:


Immune reconstitution inflammatory syndrome (IRIS) is a spectrum of clinical signs and symptoms resulting from the body's ability to mount an inflammatory response associated with immune recovery in patients of the human immunodeficiency virus (HIV) infection after initiation of highly active antiretroviral therapy (HAART).[1] It is seen most often when patients with initial low CD4 cell counts, usually <100 cells/mm3, experience a significant increase in cell counts within 6 weeks to 6 months of treatment.[1],[2] The cutaneous manifestations are among the most common presentations.[2],[3]

A 42-year-old male was diagnosed with HIV infection and cerebral toxoplasmosis, with an absolute CD4+ T-cell count of 59. He was started on HAART subsequent to the resolution of acute symptoms with anti-toxoplasmosis treatment. A dermatology consultation was sought for an associated 1-month history of asymptomatic lesions over the pubic area. On examination, multiple, verrucous, pearly white umbilicated waxy papules were present over the pubic area around the root of the penis [Figure 1]. Histopathology was confirmatory for molluscum contagiosum (MC) [Figure 2]. Topical imiquimod cream 5% was prescribed at bedtime on alternate days for 6–8 h, to be washed thereafter.{Figure 1}{Figure 2}

After 10 weeks, the patient presented with seizures and ulceration of skin lesions. He was diagnosed with worsening cerebral toxoplasmosis and was managed with anti-epileptics, dexamethasone course while continuing HAART and toxoplasmosis treatment. His CD4 count had improved to 161. The ulceration of skin lesions had started after 8 weeks of initiation of HAART and had initial perilesional erythema followed by ulceration and bleeding. On examination, the MC lesions were erythematous with most showing extensive ulceration with hemorrhagic crusting [Figure 3]. Imiquimod was stopped and topical antibiotic cream was started to prevent secondary bacterial infection. The ulceration, as well as the lesions, resolved gradually over a few weeks [Figure 4].{Figure 3}{Figure 4}

In immunocompetent patients, MC lesions have a typical morphology and usually regress spontaneously.[4] Sometimes, an inflammatory phenomenon precedes the disease resolution and is well recognized by the acronym “BOTE” sign (for “beginning of the end”).[3] It signifies inflammation due to the immune response to the MC virus.[5]

In HIV infection, the MC lesions have been known to be persistent, deforming, and atypical but resolve in most after initiation of HAART.[3],[4] However, a case report on IRIS has been published where a patient developed extensive MC lesions shortly after being started on HAART which healed spontaneously with the progression of immune reconstitution.[1] While another report describes an inflammatory reaction in MC in a child as an IRIS manifestation.[3]

IRIS occurs primarily due to an increase in the production of potent pro-inflammatory cytokines (interleukin-2, interferon-gamma), leading to inflammation of the preexisting infections and apparent worsening of the disease.[1] The severe “BOTE” sign seen in this case can be explained by this inflammatory surge due to IRIS.[5] Furthermore, a clear time correlation with immunological reconstitution after initiating HAART indicates that the severe BOTE sign seen in MC lesions, in this case, is most likely an IRIS manifestation.

Most of IRIS cases are self-limiting and require only symptomatic treatment, although in severe cases anti-inflammatory drugs or corticosteroids may be used.[1] A knowledge about the “BOTE” sign and its varied presentation in immunocompromised individuals as possible IRIS manifestation is important as no active intervention is needed and a spontaneous resolution is likely to occur with the continuation of HAART.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Pereira B, Fernandes C, Nachiambo E, Catarino MC, Rodrigues A, Cardoso J. Exuberant molluscum contagiosum as a manifestation of the immune reconstitution inflammatory syndrome. Dermatol Online J 2007;13:6.  Back to cited text no. 1
National AIDS Control Organization. National Technical Guidelines on Anti-Retroviral Treatment. Available from: (1).pdf. [Last accessed on 2021 Feb 24].  Back to cited text no. 2
de Carvalho VO, Cruz CR, Noronha L, Abagge KT, Lima HC. An inflammatory reaction surrounding molluscum contagiosum as possible manifestation of immune reconstitution inflammatory syndrome in HIV infection. Pediatr Dermatol 2010;27:631-4.  Back to cited text no. 3
Buckley R, Smith K. Topical imiquimod therapy for chronic giant molluscum contagiosum in a patient with advanced human immunodeficiency virus 1 disease. Arch Dermatol 1999;135:1167-9.  Back to cited text no. 4
Butala N, Siegfried E, Weissler A. Molluscum BOTE sign: A predictor of imminent resolution. Pediatrics 2013;131:e1650-3.  Back to cited text no. 5


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