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A 14 ½ -year-old female is referred to the infectious diseases clinic by her dermatologist for evaluation of a positive purified protein derivative skin test.
Her dermatologist had initially diagnosed her with a severe, chronic, ulceronecrotic form of pityriasis lichenoides et varioliformis acuta (PLEVA) that was resistant to 1 month of conventional therapy with psoralen plus UV-A light (PUVA), and doxycycline. A PPD was done by protocol in anticipation of beginning a course of methotrexate. Because she had emigrated from Pakistan about 7 months earlier, it was known that she had received a couple of doses of bacillus Calmette-Guérin vaccine in her past medical history. Therefore, she had a gamma-interferon release assay (T-spot), which was also positive. Subsequent to this, she presented evidence that her PPD was actually negative at the point of emigration. Taken at face value, it would appear that she became infected with Mycobacteria tuberculosis shortly before leaving Pakistan or soon after arrival in the United States. Similarly, the rash was first noted within a month of arrival to the US (about 6 months ago), and has been progressive.
James H. Brien
Her undocumented past medical history is also complicated by having been diagnosed with possible juvenile idiopathic arthritis or rheumatic fever (not sure which), according to her mother’s interpreter, a few years earlier in Pakistan. However, whatever that illness was, she had a history of recovery before emigrating and was on no medications. Having said that, she is currently being followed by a pediatric rheumatologist for chronic, recurrent joint pain, with no confirmed rheumatologic diagnosis. Other than these problems with this foggy history, she is fairly healthy and academically very bright.
Initial examination revealed a very pleasant and articulate adolescent female with normal vital signs, with the only positive finding being a rash consisting of numerous hyperpigmented, somewhat depressed, ulcerative lesions on the extensor surfaces of the lower legs, and scaly, pink papular lesions on the forearms (Figures 1 and 2). Additionally, there were some lesions on the dorsal surface of the feet. Her chest radiograph was clear, and she had no clinical evidence of TB disease. Her lab tests — CBC, chemistries, inflammatory markers and urinalysis — as well as numerous special rheumatologic tests (ANA, P-ANCA, C-ANCA, etc.) were all normal or negative. A biopsy of a skin lesion is shown in Figure 3; a high-powered view showing granulomatous inflammation, composed of epithelioid histiocytes. Acid-fast stains and culture of the tissue were negative, as well as PCR testing for M. tuberculosis.
Initial examination revealed an adolescent female with normal vital signs, with the only positive finding being a rash consisting of numerous lesions on the extensor surfaces of the lower legs, and scaly, pink papular lesions on the forearms (Figures 1 and 2).
Source: Brien JH
A biopsy of a skin lesion is shown in Figure 3. However, within 6 months she was back in the ID clinic with a recurrence of the skin lesions (Figure 4).
Isoniazid (INH) therapy for latent tuberculosis infection (LTBI) was initiated, which she tolerated well. On follow-up within a few weeks, it was noted that the rash was somewhat improved, and by the end of the 9 months of therapy, the rash had resolved (no pictures taken). However, within 6 months she was back in the ID clinic with a recurrence of the skin lesions (Figure 4).
What’s Your Diagnosis?
A. Langerhans cell histiocytosis
B. Severe PLEVA
C. Papulonecrotic tuberculid
D. Henoch-Schönlein purpura
Case Discussion
The answer turned out to be C, papulonecrotic tuberculid. This is caused by a hypersensitivity reaction to M. tuberculosis infection, either LTBI or active disease, that leads to vasculitis, either by immune complex deposition or by subacute lymphohistiocytic vasculitis and thrombosis. Either way, necrosis is the common end result, with granulomatous skin lesions containing epithelioid histiocytes, but without evidence of the organism (TB) in the lesion. Also, treating the TB usually results in improvement of the rash, which can be used as a diagnostic test, as well. Even though our patient improved with only INH prophylaxis alone, it was temporally associated with this treatment and the rash returned within a few months of discontinuing the INH. At this point, we were fairly certain of this diagnosis, and treated her for M. tuberculosis disease with four-drug therapy (INH, rifampin, ethambutol and pyrazinamide) per AAP Red Book guidelines. There was rapid cessation of new lesions and gradual healing of those remaining (Figure 5, taken 2 months after Figure 4). Note comparable pictures showing the changes in some discrete lesions over time in Figure 6. As of this writing (October 2014), she was rash-free and her joints also stopped hurting. This raises the question of whether she also may have had Poncet disease (reactive arthritis due to TB infection). The only problem with this is that Poncet disease has only been described in those with active TB disease, not LTBI, at least so far.
Langerhans cell histiocytosis was formerly known as histiocytosis X, with three subtypes: Letterer-Siwe disease, Hand-Schüller-Christian disease and eosinophilic granuloma. However, more contemporary description considers this as a spectrum of one disorder and discourages the use of these history terms. This is an infiltrative disease of histiocytes that have a characteristic appearance, including large, oval-shaped cells with a pink (eosinophilic) granular cytoplasm. Skin lesions can certainly be seen as a feature of this, but usually resemble a chronic, unresponsive eczema-like rash, rather than necrotic lesions.
There was rapid cessation of new lesions and gradual healing of those remaining (Figure 5, taken 2 months after Figure 4). Note comparable pictures showing the changes in some discrete lesions over time in Figure 6.
Your test-taking skills should lead you away from PLEVA. This is a papulosquamous disorder of varying degrees of severity that results in an acute development of a papulovesicular inflammatory lesions that develop a necrotic crust, making it easy to confuse with papulonecrotic tuberculid. However, the clues were a lack of improvement with PUVA and doxycycline therapy, and improvement with INH.
Henoch-Schönlein purpura is an IgA-mediated autoimmune small-vessel vasculitis, with characteristic skin manifestations including a maculopapular rash with some petechiae and purpuric lesions (palpable or allergic purpura). Other organ systems can be involved — GI and renal, most commonly. The condition is typically self-limiting, requiring no treatment, but some experts use steroids for severe cases, especially with GI manifestations, with some limited supportive data.
For more information:
James H. Brien, DO, is with the department of infectious diseases at McLane Children’s Hospital, Baylor Scott & White Health, Texas A&M College of Medicine in Temple, Texas. He is also a member of the Infectious Diseases in Children Editorial Board. Brien can be reached at: jhbrien@aol.com.
Disclosure: Brien reports no relevant financial disclosures.