Papulonecrotic tuberculide and stenosis of the abdominal aorta

V. Kontogiannis, K. L. Dalziel1 and R. J. Powell3

Clinical Immunology Unit, Queens Medical Centre, Nottingham and
1 Department of Dermatology, Queens Medical Centre, Nottingham NG7 2UH, UK

Abstract

Papulonecrotic tuberculide (PNT) is a rare form of skin tuberculosis affecting predominantly young adults, with a history of immunity to Mycobacterium tuberculosis. We report a case of a young Caucasian female with PNT who was also documented to have a stenotic segment in the abdominal aorta. The difficulty in clarifying and treating the primary disease and the association between a tuberculous infection and Takayasu's arteritis are discussed.

KEY WORDS: Papulonecrotic tuberculide, Takayasu's arteritis, Aortitis, Granulomatous vasculitis

A 14-yr-old girl presented with a purple reticulate rash over the lateral border of both feet (Fig. 1Go), livedo reticularis on both knees (Fig. 2Go), chilblains and ulcers on her toes, an erythematous rash on her elbows and arthralgias of knees and ankles for 6 months. Similar chilblain-like lesions had appeared in the two previous winters tending to settle in the summer but this time they persisted. Individual toe ulcers would heal followed by the eruption of new lesions. Her history included familial hypermobility, eczema and hay fever. She did not have Raynaud's, photosensitivity, synovitis, muscle weakness or pain and the peripheral pulses were present. Investigations were unremarkable except for a slightly elevated erythrocyte sedimentation rate (ESR) at 25 mm/h and a polyclonal increase in serum IgG 22.5 g/l. Lesional skin biopsy from the knee showed necrobiotic granulomas in the dermis and circumscribed areas of collagen degeneration but no evidence of vasculitis. These changes were considered compatible with granuloma annulare.



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Fig. 1. Bilateral, purple, reticulate rash on feet.

 


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Fig. 2. Livedo reticularis confined to both knees.

 
No treatment was given as granuloma annulare is usually a self-limiting condition. Fifteen months after the initial presentation she developed many painless ulcers on her toes (Fig. 3Go) and the ESR had further increased to 41 mm/h. Further skin biopsies from the knee showed granulomatous vasculitis and panniculitis in the mid and deep dermis and giant cell granulomatous inflammation in the dermis (not vessel-based) and from the elbow granulomatous inflammation of the dermis and circumscribed areas of collagen degeneration. An opacification in her right upper lobe, a history of a very strongly positive heaf test in the absence of BCG inoculation and that her aunt had been previously treated for tuberculosis were all documented at this time. As the diagnosis of papulonecrotic tuberculide (PNT) was considered likely she was treated with isoniazid 300 mg once daily (o.d.), rifampicin 450 mg o.d., and pyrazinamide 1.5 g o.d. Pyrazinamide was discontinued after 2 months. After 4 months some improvement in the rash on her toes was noted but the partial response to treatment was not typical of PNT. Polymerase chain reaction (PCR) studies of a skin lesion failed to demonstrate mycobacterial DNA. Alternative diagnoses such as cutaneous polyangiitis were also considered leading to treatment with methotrexate 10 mg weekly, increasing to 15 mg weekly with folic acid supplementation. After 6 months, anti-tuberculous therapy was stopped. The ESR was 9 mm/h and although the rashes, livedo and feet pain were still present the toe ulcers were healed. Eight months later she had a new episode of toe ulcers (ESR 41 mm/h) which responded to a 4-week course of prednisolone at a starting dose of 20 mg/day. Methotrexate was discontinued after 11 months due to gastrointestinal side-effects and lack of further improvement.



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Fig. 3. PNT. Multiple painless ulcers on toes bilaterally.

 
During a routine clinical review, an asymptomatic abdominal bruit and thrill were noted. Extensive investigations including abdominal ultrasound, computed tomography (CT), magnetic resonance (MR) angiography and digital subtraction angiography confirmed a 4-cm long fusiform narrowing of the abdominal aorta with some thickening of the wall commencing just below the renal arteries (Fig. 4Go). The diameter of the narrowed segment was 6.7 mm whereas the distal part of the abdominal aorta had a diameter of 13 mm. No other abnormalities were identified in the rest of the aorta and its major branches.



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Fig. 4. Fusiform stenosis of the abdominal aorta.

 
Over the following 8 months she had two new outbreaks of toe ulcers both responding satisfactorily to 2–3-week courses of low doses of prednisolone. At present, 24 months after the last episode she remains very well on no treatment. She still has livedo on her knees and a purplish rash on her feet, but these are much less prominent. The rash on her elbows and the ulcers have not recurred and two follow-up abdominal ultrasounds have not revealed changes in the abdominal aortic lesion.

Discussion

PNT is a rare condition regarded as a hypersensitivity reaction to Mycobacterium tuberculosis following haematogenous spread from a focus of infection in individuals with significant immunity manifested by a strongly positive tuberculin test. It typically affects young adults, especially females, involving symmetrically the extremities of the limbs, the ears and the extensor aspects of joints. The individual lesion is an inflammatory papule which becomes necrotic, ulcerates and involutes over weeks leaving scars in many cases [1, 2]. Chilblain-like lesions with a tendency to deteriorate in the winter and settle in the summer are reported [3] and are largely symptomless in most cases. The tuberculin test is usually strongly positive and often there is clinical evidence of previous mycobacterial infection and the histological picture does not resemble that of a tuberculoid or sarcoid granuloma [3]. Atypical papular tuberculide may follow BCG vaccination [2]. Epidermal ulceration, dermal coagulative necrosis, granulomatous infiltrate (often resembling granuloma annulare), granulomatous vasculitis and extravasation of red cells are common findings [1, 2, 4]. Mycobacterial DNA has been demonstrated in several cases using a PCR technique (a negative result does not exclude the diagnosis) but never the whole pathogen [1, 5]. Combination anti-tuberculous therapy should lead to rapid resolution of the lesions [14, 6].

Takayasu's arteritis (TA) is an unusual systemic inflammatory disease usually involving the aorta and/or its major branches. Associated skin lesions can be erythema nodosum, erythema induratum, tuberculide-like eruptions, pyoderma gangrenosum, urticarial lesions, livedo reticularis and cutaneous signs of necrotizing or granulomatous vasculitis [79]. Diagnosis is usually delayed because of a non-specific initial clinical presentation, silent progress and variable natural history. ESR is usually elevated, and a clinical response to steroids and cytotoxics (i.e. methotrexate or cyclophosphamide) is reported [10].

Tuberculous aortitis is another rare entity where the vessels can be involved by direct extension from adjacent tuberculous tissue or occasionally blood-borne seedling from a distant focus via the vasa vasorum resulting in a stenosis [11].

In this case the diagnosis at presentation was granuloma annulare and particularly perforating granuloma annulare can be confused with PNT both clinically and histopathologically. The subsequent establishment of a previous M. tuberculosis exposure and immunity was illuminating. The patient's age, clinical picture and histopathology findings favoured the diagnosis of PNT, however the outcome of triple therapy was not as anticipated for this condition, although a partial improvement was noted. The lack of full response could be explained by possible drug resistance or methotrexate's immunosuppressive action and in retrospect a fourth agent (i.e. ethambutol) might have had additional value [2]. There is a patient reported with a positive PCR who did not respond to combination therapy and another who had relapses for 9 yr after anti-tuberculous therapy before remitting spontaneously [5].

The differential diagnosis in our case hinges between PNT coexisting with a tuberculous aortitis or a manifestation of a limited form of TA, possibly associated with the previous mycobacterial infection, although the revised [12] and the American College of Rheumatology (ACR) [13] criteria for the classification of TA are not fulfilled. Many authors have pointed out a possible tuberculous aetiology for TA [3, 1416] and some even suggested anti-tuberculosis therapy as part of its treatment. Morrison and Fourie have described idiopathic gangrene of the extremities in 8% of their patients with PNT which improved after anti-tuberculosis therapy [4]. In a recent study the association between tuberculosis and TA was almost absolute in Black South African children [17]. Furthermore, mycobacterial antigens were demonstrated on spindle-shaped cells of the aorta in patients with TA but not in healthy controls and patients with tuberculosis [18]. In one case with pulmonary tuberculosis and TA, anti-tuberculosis therapy led to the return of the previously lost right radial pulses [15]. In a case with PNT and proven TA of the aorta and its major branches, anti-tuberculosis treatment was effective for PNT but failed to resolve TA [1]. The fact that erythema induratum and tuberculoid-like eruptions have been described in cases of TA [7], provides some evidence for the association. However, against this association is the finding that TA is becoming increasingly recognized even in countries where tuberculosis is rare [11, 19].

We have not opted for long-term anti-tuberculous therapy as has been suggested [6] because the patient has remained in remission and we considered the organized aortic lesion is unlikely to respond to further treatment. The problems in accurately diagnosing and treating these cases are underlined by this case report.

Notes

3 Correspondence to: R. J. Powell. Back

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Submitted 21 October 1998; revised version accepted 8 September 1999.



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