Immune Restoration Disease After Antiretroviral Therapy

Martyn A. French; Patricia Price; Shelley F. Stone

Disclosures

AIDS. 2004;18(12) 

In This Article

Sarcoid Immune Restoration Disease

Granulomatous inflammation of the lungs, which has the characteristics of sarcoidosis, has been described in patients responding to HAART.[121,122,123,124,125,126,127] Granulomatous inflammation of other organs has also been described, including the skin ([122,128,129]; and Fig. 2a), kidneys, liver and duodenum.[130] In a study undertaken on patients presenting to five pneumonology departments, Foulon et al.[127] reported that cases presented from 3 to 43 months after commencing HAART. HIV-associated sarcoidosis has been reported in patients not receiving HAART[125] but this is characterized by a CD8 T-cell alveolitis whereas sarcoid IRD is associated with an intense CD4 T-cell alveolitis and a CD4 T-cell infiltrate in granulomas.[121,127] The involvement of CD4 T cells in the pathogenesis of sarcoid IRD may explain the occurrence of this disorder after the addition of interleukin-2 therapy to HAART.[121,124,127] It is important to exclude infectious IRD as a cause of granulomatous inflammation because this may occur in patients infected by mycobacteria, cryptococci (see above) and histoplasma (Fig. 2b).

Different causes of granulomatous inflammation in HIV patients with immune restoration disease (IRD). (a) Sarcoid IRD after commencing highly active antiretroviral therapy (HAART). A 43-year-old man with a CD4 T-cell count of 6 × 106 cells/l resumed HAART after a break of 18 months. Five weeks later he developed skin lesions when the CD4 T-cell count was 30 × 106 cells/l and the plasma HIV RNA level had fallen by > 2 log10 copies/ml. A skin biopsy showed granulomatous interstitial dermatitis. Comprehensive investigations did not demonstrate a pathogen. The lesions resolved with the use of topical corticosteroid therapy. (b) Histoplasma IRD after commencing HAART. A 23-year-old Vietnamese-Australian woman commenced HAART with a CD4 T-cell count of 12 × 106 cells/l. Within a week she developed a diffuse papulo-pustular skin eruption and at day 14 had diffuse reticulo-nodular pulmonary infiltrates on her chest X-ray. Histoplasma capsulatum was isolated from the skin and lungs. She received intravenous amphoteracin and itraconazole maintenance therapy. Ten months after commencing HAART she presented with cervical and supraclavicular lymph node enlargement. The most recent CD4 T-cell count was 56 × 106 cells/l. A fine needle aspiration of a lymph node showed necrotizing granulomatous lymphadenitis. Micro-organisms were not seen but Histoplasma capsulatum was isolated after 12 weeks culture. The lymphadenitis resolved without additional treatment.

Different causes of granulomatous inflammation in HIV patients with immune restoration disease (IRD). (a) Sarcoid IRD after commencing highly active antiretroviral therapy (HAART). A 43-year-old man with a CD4 T-cell count of 6 × 106 cells/l resumed HAART after a break of 18 months. Five weeks later he developed skin lesions when the CD4 T-cell count was 30 × 106 cells/l and the plasma HIV RNA level had fallen by > 2 log10 copies/ml. A skin biopsy showed granulomatous interstitial dermatitis. Comprehensive investigations did not demonstrate a pathogen. The lesions resolved with the use of topical corticosteroid therapy. (b) Histoplasma IRD after commencing HAART. A 23-year-old Vietnamese-Australian woman commenced HAART with a CD4 T-cell count of 12 × 106 cells/l. Within a week she developed a diffuse papulo-pustular skin eruption and at day 14 had diffuse reticulo-nodular pulmonary infiltrates on her chest X-ray. Histoplasma capsulatum was isolated from the skin and lungs. She received intravenous amphoteracin and itraconazole maintenance therapy. Ten months after commencing HAART she presented with cervical and supraclavicular lymph node enlargement. The most recent CD4 T-cell count was 56 × 106 cells/l. A fine needle aspiration of a lymph node showed necrotizing granulomatous lymphadenitis. Micro-organisms were not seen but Histoplasma capsulatum was isolated after 12 weeks culture. The lymphadenitis resolved without additional treatment.

Sarcoid IRD may resolve spontaneously with continuation of HAART but corticosteroid therapy is sometimes necessary.[127]

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