Papulonecrotic Tuberculid with Positive Acid-fast Bacilli.

Two patients suffered from 'boils' on their arms and/or thighs for several months. A diagnosis of papulonecrotic tuberculid (PNT) was made based on clinical, laboratory parameters, histopathology, and a prompt response to multi-drug anti-tuberculosis treatment. We checked the pathological sections carefully and finally found a small amount of positive acid-fast bacilli. We analyzed the clinical and histopathological features of PNT in order to offer reference of preventing and controlling the disease.

What was known?

Mycobacterial tuberculosis DNA sequences can be detected by PCR in PNT lesions. Most of the PNT patients have a prompt response to the anti-tuberculosis therapy.

Introduction

PNT is a relatively uncommon manifestation of cutaneous tuberculosis. In true cutaneous tuberculosis, there is a well-defined tuberculous origin. In PNT, the pathogenesis has been considered to be a hypersensitivity reaction to hematogenous spread of Mycobacterium tuberculosis or the fragments released from a different site of present or past tuberculosis,[1] whilst the actual relationship to tuberculosis is less clear so far.

Case Reports

Case 1

An 11-year-old Chinese boy presented to our clinic with recurrent ‘boils’ on his face, forearms, and thighs without low fever or cough since last month. The boils were non-tender. His uncle got the diagnosis of pulmonary tuberculosis for half a year. Physical examination revealed pea-sized to coin-sized (0.5 cm to 2.0 cm in diameter) atrophic and crusted ulcers symmetrically located around his face, forearms, and thighs, interspersed with varisized papules, nodules, and pustules [Figure 1]. Routine hemogram, urinalysis, liver and renal profiles were within normal limits. The erythrocyte sedimentation rate was 5 mm/hour. Culture of the sputum and urine were negative for Mycobacteria. A chest X-ray examination was performed, and cord-like shadow was found in the middle lobe of right lung and showed ‘sclerosis.’ The laboratory test of purified protein derivative (PPD) was strongly positive (72 hours): 30 × 30 mm. The Mycobacterium tuberculosis antibody (TB-IgG, produced by Beijing WANTAI Biological Pharmacy Enterprise Co., Ltd.) was positive. Biopsy specimen taken from a large crusted ulcer on the left forearm showed focal epidermal necrosis, below which lay an area of caseous necrosis, surrounded by a dense, palisade of inflammatory infiltrate filling the entire dermis that included histiocytes, lymphocytes, neutrophils, and numerous multinucleate giant cells [Figure 2]. The dermal vessels showed evidence of vasculitis. Positive acid-fast bacilli were found [Figure 3]. GMS stain and PAS stain were negative for fungi. Mycobacterium tuberculosis DNA sequences were confirmed by real-time polymerase chain reaction (Real-Time PCR) using slices of wax block of the lesion. In view of the clinical, laboratory parameters, and the histopathology, a diagnosis of PNT was made. The boy's weight was 33.5 kg. Treatment was begun with isoniazid, 300 mg/day, pyrazinamide, 750 mg/day, and rifampin, 450 mg/day, for 2 months and was followed by isoniazid, 300 mg/day, and rifampin, 450 mg/day, for 4 months. One month later, all the lesions regressed obviously. There was no recurrence for 8 months after the cessation of treatment. He is currently still on follow-up.

Figure 1

(a-c) Papulonecrotic tuberculid lesions of case one before treatment. Pea-sized to coin-sized atrophic and crusted ulcers symmetrically located around his forearms, thighs and face, interspersed with papules, nodules and pustules. (d-f) Papulonecrotic tuberculid lesions of case one after one-month treatment. All the lesions regressed obviously without new lesions occuring

Figure 2

(a) Histology shows an area of caseous necrosis (Hematoxylin-eosin stain; original magnification ×200). (b) A dense, palisade of inflammatory infiltrate that included histiocytes, lymphocytes, neutrophils and numerous multinucleate giant cells (Hematoxylin-eosin stain; original magnification ×200)

Figure 3

A small amount of positive acidfast bacilli were found in case one. (a) Acid-fast Stain; original magnification ×200. (b) Acid-fast Stain; original magnification ×400

Case 2

A 24-year-old Chinese female presented to our clinic with recurrent ‘boils’ around her thighs without low fever or cough since the last 4 months. The boils were non-tender, and some of them had healed spontaneously, leaving behind unsightly scars. Her grandmother got the diagnosis of pulmonary tuberculosis several years ago. Physical examination revealed pea-sized (0.3 cm to 0.5 cm in diameter) crusted papules symmetrically located around both her thighs, interspersed with nodules and pustules of similar size [Figure 4]. Routine hemogram, urinalysis, liver and renal profiles were within normal limits. The erythrocyte sedimentation rate was 25 mm/hour. Culture of the sputum and urine were negative for Mycobacteria. A chest X-ray and computed tomography examination were performed, and a cord-like shadow in the upper lobe of right lung was also found. The laboratory test of PPD was positive (72 hours): 20 × 20 mm. The Mycobacterium tuberculosis antibody (TB-IgG) was positive too. Ultrasound of her abdomen and pelvis were reported normal. Biopsy specimen taken from a crusted papule on the left thigh showed focal epidermal necrosis, below which lay an area of caseous necrosis, surrounded by a distinct, mixed inflammatory infiltrate filling the entire dermis that included histiocytes, lymphocytes, and multinucleate giant cells [Figure 5]. The dermal vessels showed evidence of focal lymphohistiocytic vasculitis. Positive acid-fast bacilli were also found [Figure 6]. GMS stain and PAS stain were negative for fungi. Mycobacterium tuberculosis DNA sequences were also confirmed by Real-Time PCR in the lesion. In view of the clinical, laboratory parameters, and the histopathology, a diagnosis of PNT was made. Treatment was also started with isoniazid, 300 mg/day, pyrazinamide, 750 mg/day, and rifampin, 450 mg/day, for 2 months and was followed by isoniazid, 300 mg/day, and rifampin, 450 mg/day, for 4 months. Significant clinical improvement was noted within one month. There was no recurrence for 5 months after the cessation of treatment. She is currently still on follow-up too.

Figure 4

(a) Papulonecrotic tuberculid lesions of case two before treatment. Soybean-sized crusted papules symmetrically located around both her thighs, interspersed with nodules and pustules. (b) Papulonecrotic tuberculid lesions of case two after one-month treatment. Significant clinical improvement was noted without new lesions occuring

Figure 5

(a) Histology shows an area of caseous necrosis surrounded by a distinct, mixed inflammatory infiltrate that included histiocytes and lymphocytes (Hematoxylin-eosin stain; original magnification ×200). (b) A distinct, mixed inflammatory infiltrate that included histiocytes, lymphocytes and multinucleate giant cells (Hematoxylin-eosin stain; original magnification ×200)

Figure 6

A small amount of positive acidfast bacilli were also found in case two. (a) Acid-fast Stain; original magnification×200. (b) Acid-fast Stain; original magnification ×400

Discussion

PNT is a rare skin manifestation. Since Mycobacteria cannot usually be cultured from these lesions, the controversy about the origin of PNT has been going on for many years. It has been thought that they represent hypersensitivity reactions to hematogenously disseminated bacilli or Mycobacterial antigens.[2] PNT is considered a sign of a good immunological status, because it usually appears in patients with a moderate or high degree of immunity.[3] In previous reports, PNT mostly occurred in young adults and children.[4] Moreover, they are most often seen in young adults and children with active tuberculous disease elsewhere.[5] Bacilli are usually absent, but the PPD should be strongly positive.[5] Our patient were both young people, and the extraordinary big ulcers of case one maybe suggested higher immune ability.

PNT was regarded as an allergic reaction against Mycobacterium tuberculosis in tuberculous lesions of other organs.[6] There are many reports which showed that Mycobacterium tuberculosis DNA sequences can be detected by PCR in PNT lesions.[78] E. Quirós et al. had demonstrated the presence of Mycobacterium tuberculosis DNA by PCR in the lesions of 80% of their PNT patients.[2] Up to the present, there is no report describing a case of PNT with positive acid-fast bacilli in the slices of the lesion. It's difficult to find the positive acid-fast bacilli in the pathological sections of the PNT lesion, and we checked the slices several times carefully and finally found a small amount of positive acid-fast bacilli. Mycobacterium tuberculosis DNA sequences were also confirmed by Real-Time PCR in the lesion of both our patients. After reviewing the literature, we believe this is the first time that PNT lesions have been revealed by histological examination for the presence of Mycobacterium tuberculosis. These findings provide direct proof that Mycobacterium tuberculosis are present in PNT lesions and support the theory that this organism is really responsible for the development of PNT. There is only a small amount of positive acid-fast bacilli, maybe caused by the higher immunological reaction in the local derma, and plenty of bacilli had been phagocytosed and eliminated by phagocytes. PNT can be considered to represent the paucibacillary pole of blood-borne disseminated tuberculosis, as opposed to the multibacillary picture of acute milliary tuberculosis.[5]

Some studies have shown the existence of an extracutaneous focus in 40-70% case.[46] There were evidences of previous pulmonary tuberculosis with the both our patients, and both of them had a family history of tuberculosis. Therefore, the patient who get the probable diagnosis of PNT clinically need to have the overall physical and laboratory examinations and try to find out the primary lesion. It indicated that PNT lesions were probably hematogenous in origin and not primary vasculitis.

In PNT, prompt response to anti-tuberculosis treatment is its hallmark. However, several reports showed that a number of skin manifestations disappeared quickly without any anti-tuberculosis therapy, suggesting the patients had a high degree of immunity.[910] Nonetheless, most of the PNT patients generally have no tendency for spontaneous remission, and they usually receive some anti-tuberculosis therapy. We give the patients multi-drug anti-tuberculosis therapy, and they both have a prompt response to the treatment.

It provides a rational basis for anti-tuberculosis therapy of PNT and for the clinical management of these disorders. Number of the PNT cases was so limited, and we need more cases to confirm the verdict.

What is new?

Positive acidfast bacilli can be found by histopathological examination in PNT lesions.