Possible immune reconstitution inflammatory syndrome due to Mycobacterium colombiense skin infection in a person living with HIV/AIDS

Dear Editor,

Opportunistic mycobacterial infections are a frequent cause of morbidity and mortality in people living with human immunodeficiency virus (PLWH); non-tuberculous mycobacteria (NTM) have a mortality rate close to 30%, including patients under antiretroviral treatment (ART).¹ Mycobacterium colombiense (M. colombiense) is part of the Mycobacterium avium complex (MAC) with pulmonary and systemic involvement.² Skin infection is rare, with only two isolated cases reported so far.^3,4 We present a case of a 55-year-old woman with systemic arterial hypertension, who presented with asthenia, adynaemia, diarrhoea, and unintentional weight loss of 20 kg in the last 8 months. An HIV viral load of 3,08,408 copies/mL (log 5.4) and CD4+ T-lymphocyte count of 33 cells/mm³ were documented. She was hospitalised for diarrhoeal syndrome associated with Cytomegalovirus and Sapovirus infections demonstrated by stool culture and colonoscopy. Chest X-ray showed no alterations. Consumptive syndrome secondary to HIV in stage B3 of acquired immunodeficiency syndrome (AIDS) was diagnosed. She was started on ART with bictegravir, emtricitabine, and tenofovir alafenamine.

One month later she presented with erythematous, hyperpigmented, and painful nodules on the medial side of the thighs. The patient reported night sweats without fever or other constitutional symptoms. A fine needle aspiration (FNA) biopsy from the nodule showed acid-alcohol-resistant bacillus (ARB). Awaiting genotyping and culture results, she presented with a 10-cm ulcer in the gluteal area with poorly defined erythematous borders and necrosis [Figure 1]. Skin biopsy revealed chronic on acute ulcerative dermatitis with negative staining for mycobacteria. Three weeks later, the nodular lesions spread to the lower extremities, and a second skin biopsy was taken. Histopathologic examination revealed hyperkeratosis, spongiosis, neutrophilic infiltrate and exocytosis, mixed inflammation in reticular dermis as well as lobular panniculitis [Figure 2a]. Lymphocytes, macrophages, and plasmatic cells were present at higher magnification (200 µ) [Figure 2b]. Periodic acid Shiff, Ziehl-Neelsen, and Grocott stains were negative; however, cultures and DNA sequencing of both biopsies were positive for M. colombiense. Unmasked immune reconstitution inflammatory syndrome (IRIS) due to mycobacterial skin infection was diagnosed, with an undetectable CV (log <1.6) and CD4+ a T-lymphocyte count of 74 cells/mm³.

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Figure 1:

Necrotic ulcer in the gluteal area with boggy erythematous borders.

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Figure 2a:

Panoramic haematoxylin and eosin stain showing hyperkeratosis with neutrophilic infiltrate, spongiosis, and exocytosis, as well as a lobular panniculitis with mixed inflammation in reticular dermis (Haematoxylin and eosin, 40x).

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Figure 2b:

At higher magnification lymphocytes, macrophages, and plasmatic cells are present (Haematoxylin and eosin stain, 100x).

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The patient was started on the 4-antituberculous drug scheme, including daily rifampicin (150 mg), isoniazid (75 mg), pyrazinamide (400 mg), and ethambutol (300 mg), plus clarithromycin (500 mg) every 12 hours for 12 months. ART was modified to tenofovir disoproxil succinate, emtricitabine, and dolutegravir to avoid drug interactions. After one month of treatment, lesions improved without adverse drug reactions and no recurrence at 8 months follow-up [Figure 3].

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Figure 3:

Residual skin lesion characterised by a hyperpigmented scar at the gluteal area.

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M. colombiense is a slow-growing ARB. It was first described in 2006 in Colombia in 4 PLWH and commonly affects the lungs, lymph nodes, bones, and joints.² The organism can cause bacteraemia, especially in patients with AIDS, and with CD4 T-cell counts <50/μl.⁵ Although rare, it is associated with a higher mortality than other MAC species.⁶

Lymphadenopathies are the most common manifestation of M. colombiense infection, along with cutaneous lesions such as abscesses, nodules, or ulcers. However, there are only two reported cases of isolated cutaneous involvement [Table 1]. In a study from China, 248 non-HIV patients were analysed and only nine presented with M. colombiense infection. Of these, five had cutaneous manifestations such as abscesses, nodules, or ulcers. However, no exclusive cutaneous infection was reported.⁵

With the advancement of technology comes genetic sequencing, which is the reference method to identify species, even rare ones. However, culture continues to be vital since it allows drug susceptibility tests.⁷ There is no consensus on the optimal antimicrobial regimen for M. colombiense. As drug susceptibility testing indicates a strong similarity with MAC, established guidelines are followed with clarithromycin (500 mg) every 12 hours and ethambutol (15 mg/kg/day) for at least 12 months.^2,6

On the other hand, it should be considered that late-stage HIV diagnosis and ART initiation make immune reconstitution more likely, causing IRIS. This phenomenon can manifest in two distinct ways: firstly, as a paradoxical reaction characterised by the exacerbation of pre-existing infections, and secondly, as an unmasked reaction, wherein non-diagnosed infections emerge after immune recovery, as occurred in the present patient. M. tuberculosis is the most frequent cause of IRIS in PLWH. Among the NTM, MAC involves most IRIS cases, but no information regarding M. colombiense IRIS is available. Unmasked IRIS due to M. colombiense as in this case is less frequent than the paradoxical form.

Cutaneous infection without systemic M. colombiense is a rare manifestation in PLWH. The case emphasises the crucial role of genetic sequencing in the diagnosis of atypical infections and the aetiological role of NTM infections in PLWH with IRIS