Multiple cutaneous and mucocutaneous lesions as manifestations of pseudo-Behçet’s disease

Abstract

Pseudo-Behçet’s disease (PBD) is a close clinical mimicker of Behçet’s disease (BD) which can present with orogenital ulceration and uveitis. However, these manifestations in PBD are associated with occult tuberculosis. Sometimes, diagnosis of PBD is established retrospectively when the lesions respond to anti-tubercular therapy (ATT). We here describe a case who presented with a penile ulcer, initially suspected to be a sexually transmitted infection, but was later diagnosed as PBD and resulted in complete healing with ATT. Knowledge about this condition is essential to prevent misdiagnosis as BD and unnecessary treatment with systemic corticosteroids, which can lead to worsening of tuberculosis.

Background

Behçet’s disease (BD) is a rare vasculitic disorder characterised by recurrent orogenital ulcers and uveitis. It can also present with other cutaneous manifestations like pseudo-folliculitis, erythema nodosum, pathergy phenomenon as well as other systemic manifestations.¹

However, similar mucocutaneous manifestations can also present in pseudo-BD (PBD). The term PBD refers to a condition in which the patient presents with symptoms similar to BD in association with underlying conditions like tuberculosis, and complete resolution of clinical manifestations with anti-tubercular therapy (ATT).² We here report a case who initially presented with a penile ulcer, but was later diagnosed as PBD and showed excellent clinical response to ATT.

Case presentation

A young man in his 20s presented with a non-healing ulcer over the glans penis for past the 5 months. It started as a small pustular lesion over the glans which subsequently ruptured to form a tiny ulcer which gradually progressed to involve the entire glans penis over a period of 4 months. There was a history of unprotected sexual contact with a single partner 1 year ago. There was no history of oral ulcers, joint pain, and ocular, gastrointestinal or neurological symptoms.

Mucocutaneous examination revealed an ulcer measuring around 3×2 cm involving the glans penis with non-indurated base, along with slough overlying the floor of the ulcer associated with mild tenderness and purulent discharge (figure 1). There was a single, mobile, non-tender, left inguinal lymph node measuring 2×2 cm. During the hospital stay, there was deepening of penile ulcer and the patient reported two urinary streams during micturition, which was suggestive of fistula formation. He also developed a single painful oral ulcer over the hard palate (figure 2) and pinpoint pustular eruptions over the arms (figure 3). Ocular examination findings including near and distant vision, tonometry, slit-lamp examination and ophthalmoscopy were within normal limits with no evidence of uveitis.

Figure 1.

Ulcerative lesion involving the glans penis.

Figure 2.

Oral ulcer over the hard palate (black arrow).

Figure 3.

Pustular eruption over the arm.

Investigations

The patient was initially suspected to be suffering from sexually transmitted infections (STIs); therefore, venereal disease research laboratory test and Treponema pallidum haemagglutination assay, Tzanck smear, tissue smear and swab cultures were done, which came out to be negative. A complete blood count, liver and kidney function tests, fasting and post-prandial plasma glucose levels were within normal limits. Serology for HIV 1 and 2, hepatitis B and hepatitis C viruses was non-reactive.

The erythrocyte sedimentation rate was markedly elevated to 125 mm in the first hour. For further evaluation, Mantoux tuberculin skin test was done, which was strongly positive (18 mm) at 48 hours (figure 4), while pathergy test was negative. Biopsy from the penile ulcer showed epidermis with ulceration, along with marked mixed inflammatory infiltrates and areas of necrosis and granulation tissue (figure 5A, B). Biopsy from the pustular eruption on the arms demonstrated dense perifollicular mixed infiltrates comprising of lymphocytes and neutrophils with no evidence of granuloma formation (figure 6A, B). Gram stain and bacterial culture from the pustule revealed no microorganism. Ultrasound of the abdomen, pelvis and neck revealed multiple subcentric abdominal, inguinal and cervical lymph nodes. Fine-needle aspiration cytology of the left inguinal lymph node was suggestive of reactive hyperplasia.

Figure 4.

Strongly positive Mantoux test.

Figure 5.

(A) Biopsy from the penile ulcer showing epidermis with ulceration (H&E, 4×). (B) Marked mixed inflammatory infiltrates along with areas of necrosis and granulation tissue (H&E, 10×).

Figure 6.

(A) Biopsy from the pustule on the arm showing dense inflammatory infiltrate around the hair follicle (H&E, 4×). (B) Dense perifollicular mixed infiltrates comprising of lymphocytes and neutrophils with no evidence of granuloma formation (H&E, 20×).

Contrast-enhanced CT scan of the thorax revealed patchy peribronchovascular consolidations in the apicoposterior segment of left upper lobe, which was suggestive of infective aetiology. Paraseptal emphysematous changes were also noticed in the left upper lobe. Multiple bilateral paratracheal, perivascular and axillary lymph nodes were also present. In view of the above findings, a pulmonary opinion was sought and a bronchoalveolar lavage (BAL) was done, which finally demonstrated the presence of acid-fast bacilli by Ziehl-Neelsen staining.

Differential diagnosis

The patient was initially suspected to be suffering from ulcerative STIs like chancroid, donovanosis or primary chancre. These were ruled out by negative tissue smears, Tzanck smear, cultures and serological tests. Papulonecrotic tuberculid (PNT) was considered as a differential in view of ulcerative lesions and strongly positive Mantoux test; however, oral ulcers are not seen in PNT. Moreover, skin biopsy did not reveal the presence of granulomas, which also helped to differentiate it from cutaneous tuberculosis. Lack of gastrointestinal symptoms and absence of non-caseating granulomas in the biopsy from the ulcer ruled out the possibility of metastatic Crohn’s disease. In due course of time, when the patient developed oral ulcers and pustular skin eruption, the diagnosis of BD was strongly considered. However, strongly positive Mantoux test, negative pathergy test and multiple subcentric lymph nodes in an endemic region for tuberculosis also raised the possibility of PBD. Finally, the presence of acid-fast bacilli in BAL specimen and complete response to ATT helped to diagnose the case as PBD associated with pulmonary tuberculosis.

Treatment

After confirmation of diagnosis of pulmonary tuberculosis and PBD, the patient was started on ATT (2-month intensive phase with isoniazid, rifampicin, pyrazinamide and ethambutol followed by 4-month continuation phase with isoniazid, rifampicin and ethambutol) in dosage according to body weight.

Outcome and follow-up

The patient tolerated ATT well with no adverse effects. Penile ulcer began to heal within first month of therapy with complete healing of the lesion by fourth month including healing of fistulae with some scar formation (figure 7). There was no further episode of oral ulcers and cutaneous eruption. At present, the patient has completed ATT for 6 months and is under regular follow-up with no fresh symptoms.

Figure 7.

Complete healing of the penile ulcer with some scarring.

Discussion

BD is a multisystem inflammatory disease of unknown aetiology, classified as systemic vasculitis and as neutrophilic dermatosis involving all types and sizes of blood vessels. It is characterised clinically by recurrent oral aphthous ulcers, genital ulcers, skin lesions and uveitis.^{1 2}

PBD is a condition mimicking BD, where the patient clinically presents with symptoms similar to BD like oral and genital ulcers.³ However, in PBD, these lesions are associated with underlying conditions like tuberculosis and they resolve completely with ATT. It is a rarely described condition with very few cases reported worldwide (table 1).^3–7

Table 1.

Previously reported cases of pseudo-Behçet’s disease (PBD) associated with tuberculosis^3–7

Serial no	Age	Sex	Clinical features of PBD	Associated tuberculosis	Response to ATT	Reference no
1	40s	F	Orogenital ulcers, erythema nodosum, arthritis	Tubercular lymphadenitis	Complete resolution	3
2	40s	M	Orogenital ulcers, conjunctivitis, erythema nodosum, arthritis	Papulonecrotic tuberculid	Complete resolution	4
3	20s	F	Orogenital ulcers, acne, low back pain	Pulmonary tuberculosis	Complete resolution	5
4	20s	F	Orogenital ulcers, erythema nodosum, arthritis, episcleritis, uveitis	Miliary tubercular lymphadenitis	Complete resolution	5
5	40s	F	Genital ulcers, arthritis, erythema nodosum, uveitis	Tubercular lymphadenitis	Complete resolution	6
6	40s	M	Orogenital ulceration, erythema nodosum	Tubercular lymphadenitis	Complete resolution	7
7	20s	M	Orogenital ulceration, pustular eruption	Pulmonary tuberculosis	Complete resolution	Present case report

ATT, anti-tubercular therapy.

All these cases responded completely to ATT, with symptom-free follow-up period ranging from 1 to 3 years.^3–7 In addition, three more cases of BD-like syndrome have been reported in association with viral infections, where anti-viral therapy was found to be useful in treatment.⁶

The pathogenesis of PBD in association with tuberculosis has not been elucidated well. It has been postulated that orogenital ulcers are mediated by cross-reactivity between microorganism antigens and mucosal protein, possibly acting via the 65 kD heat shock protein (HSP65) of Mycobacterium. This mycobacterial antigen has a high homology with human protein HSP60.^3–5 Genetic predisposition may also be contributory in development of these clinical manifestations.⁶ It is very difficult to clinically differentiate between BD and PBD. In such cases, a through search for underlying focus on tuberculosis is recommended. In case of strong clinical suspicion of tuberculosis, response to ex-adiuvantibus treatment with ATT will establish the diagnosis of PBD retrospectively.

Learning points.

• Pseudo-Behçet’s disease is a rare but close mimicker of Behçet’s disease (BD).

• It can occur in patients suffering from tuberculosis and responds well to anti-tubercular therapy.

• In countries like India where tuberculosis is highly prevalent, a patient presenting with manifestations of BD must be evaluated thoroughly for underlying tuberculosis.

• This will also prevent unnecessary treatment with corticosteroids and/or other immunosuppressants, which can worsen tuberculosis.

Ethics statements

Patient consent for publication

Obtained.