TB in the skin on rise? Be alert, study advises

Skin lesions part of a new syndrome

Clinicians should be on the alert for patients who show up at emergency departments with unusual skin lesions on the trunk and extremities, according to a report which appeared in a recent edition of Clinical Infectious Diseases.1 The lesions could be indicative of AIDS patients with miliary spread of tuberculosis - and such high loads of bacteria that it "seeds" into the skin, says Margaret Fischl, MD, professor of medicine at the University of Miami Department of Medicine. Though it may be only coincidence, several such patients have been infected with multidrug-resistant (MDR) TB, Fischl adds.

Evidence pointing to the existence of the unusual syndrome was uncovered during a review of cases from Florida's 1989 MDR-TB outbreak, Fischl says. Historically, miliary TB accompanied by skin lesions is extremely rare in patients over age 15. Yet Fischl and her co-workers encountered four such cases. When they searched the literature for evidence of more, they found that nine similar cases have been documented since 1991.

Connection with poor access to care?

Fischl speculates the syndrome may be especially characteristic of AIDS patients with poor access to medical care, or who defer seeking treatment until very late in the course of their illness. "In general, AIDS patients in this country are doing better, thanks to the more potent antiretrovirals and to prophylaxis for TB and other opportunistic infections," she says. "But we still see a group of patients with poor access to care; I think TB and miliary TB are still things physicians need to think about in this particular group. We thought that being on the alert for these unusual symptoms might help people recognize this."

In the four cases Fischl and her co-workers describe, the skin lesions appeared on patients' trunks, and sometimes also their extremities and faces. The lesions seemed to appear a few days after patients had been admitted to the hospital and placed on anti-TB therapy - though whether the sequence of those events is significant isn't yet clear, Fischl adds.

The lesions were striking and took the form of diffuse, pustular eruptions with erythematous bases. Within days, small fluid-filled vesicles formed on top of the eruptions. When the fluid was examined microscopically, there was evidence of necrosis and of numerous acid-fast bacilli. Eventually, the lesions resolved and were replaced by small brownish scars.

Fischl says she's not sure whether it's only coincidence that three of the four Miami cases were found to be infected with MDR-TB. Certainly, not knowing the patients had multidrug-resistant disease delayed effective treatment. "These days, of course, we'd treat them with a long list of drugs; but remember, this was all taking place at a time when people weren't alert for MDR-TB," she adds.

Fischl says she still recalls "the overwhelmingness" of how TB manifested in the patients. "The severity of the disease and its wide dissemination were quite striking," she says. Not surprisingly, three of the four patients she describes died shortly after starting anti-TB treatment; the three had MDR-TB. (A fourth patient, this one with drug-sensitive disease, was nonadherent to treatment, and was subsequently lost to follow-up.) Among the four cases, the three who were tested for CD4+ T-cell counts had results of 9, 41, and 99 cells/mm3.

Typically, hematogenous TB spreads not to the skin, but to the lungs, liver, bone marrow, lymphatic system, and spleen, Fischl says. By the same token, cutaneous forms of TB aren't usually associated with miliary TB, nor with severe immunosuppression, she adds. Most recorded cases of TB in the skin as a feature of miliary TB have occurred in infants in the pre-antibiotic era, a situation which in many ways parallels that of patients who have multidrug-resistant TB and advanced HIV disease, notes Fischl.

A more typical example of cutaneous TB is lupus vulgaris, which is associated with "a low amount of bacilli, and a fairly brisk immunologic response," Fischl says. Lupus vulgaris is also characterized by the formation of granulomata; by contrast, the lesions in the four patients Fischl and her colleagues describe showed scarcely any evidence at all of granuloma formation.

Reference

1. Daikos GL, Uttamchandani RB, Tuda C, et al. Disseminated miliary tuberculosis of the skin in patients with AIDS: report of four cases. Clin Infect Dis 1998; 27:205-208.