Papulonecrotic Tuberculid In Pregnancy – A Rare Entity

Although papulonecrotic tuberculid is an uncommon cutaneous manifestation of tuberculosis (TB) associated with Mycobacterium tuberculosis infection, the simultaneous occurrence of papulonecrotic tuberculid and erythema induratum is even rarer. Papulonecrotic tuberculid occurs predominantly in young adults and is characterized by eruptions of necrotizing papules that heal with varioliform scars. Histopathologic findings include wedge-shaped necrosis of the dermis, poorly formed granulomatous infiltration, and vasculitis. Stainings and culture for acid-fast bacilli from skin biopsies are usually negative for M.tuberculosis, although the eruptions resolve with antitubercular therapy. Few patients with papulonecrotic tuberculid, especially with concurrent occurrence of erythema induratum, have been reported in the English literature. Here we report a case of a 12-year-old girl with simultaneous occurrence of papulonecrotic tuberculid and erythema induratum accompanying pulmonary TB.

Papulonecrotic tuberculid and Poncet disease: A case of multisystem delayed-type hypersensitivity in a patient with Mycobacterium tuberculosis infection

Congenital tuberculosis manifesting as cutaneous disease.

The clinical and histopathologic findings of a rare simultaneous occurrence of papulonecrotic tuberculid and nodular tuberclid in a patient with active but asymptomatic pulmonary tuberculosis are presented. Papulonecrotic tuberculid was observed at a very early stage, presenting as molluscum-like lesions. This has been described once in the literature. This was observed in conjunction with lesions compatible with the rare clinicopathologic variant of nodular tuberculid. Critical to the diagnosis of active pulmonary tuberculosis was the use of induced sputum testing, which confirmed the diagnosis despite the lack of a cough and a chest x-ray negative for active tuberculosis. A 40-year-old male presented with a 2-week history of fever and a skin eruption consisting of molluscum-like papules on the ears, arms, and abdomen and nodules on his legs. Biopsies from both lesions were consistent with papulonecrotic and nodular tuberculid, respectively. Despite the lack of any respiratory symptoms, induced sputum grew Mycobacterium tuberculosis, and the lesions resolved on antituberculous therapy. Tuberculids are rare in Western countries but must be considered in the differential diagnosis of eruptions in patients from endemic countries. An active tuberculous focus must be sought out.

Sir, Papulonecrotic tuberculid causing penile ulcers is extremely rare.1 Herewith, we report a case of papulonecrotic tuberculide of the penis in a 56-years-old male. A 56-year-old married male patient was referred to our department with multiple asymptomatic non-healing ulcers over the glans penis of one month duration. He was a heterosexual individual and his wife did not have any genital lesions or discharge. The patient denied any history of pre-marital and extra-marital sexual contact. On physical examination, there were multiple, superficial and deep tender ulcers on the glans penis with ragged, irregular margins and floor covered with necrotic yellow slough (Fig. 1). The urethral meatus was hidden by these ulcerative lesions. Rest of the genital examination was normal. There was no inguinal lymphadenopathy. His systemic examination was unremarkable. Fig. 1 Glans penis showing multiple ulcers The hemogram revealed elevated erythrocyte sedimentation rate (50 mm in the first hour). Tuberculin (Mantoux) test was strongly positive (20 mm × 20 mm). Gram stain of the discharge from the ulcers demonstrated pus cells, Gram positive cocci, and Gram negative bacilli and discharge from the ulcers grew Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis. Ziehl Neelsen stain of the pus did not demonstrate any acid-fast bacilli (AFB). Tzanck smear from ulcer was negative for multinucleated giant cells. Urine sediment examination for AFB and urine culture were noncontributory. Radiological and ultrasound evaluation of the genitourinary system was normal. HIV antibodies test and VDRL test were nonreactive. Systemic evaluation for any focus of tuberculosis was unremarkable. Biopsy from the edge of the ulcer (glans penis) revealed ulcerated epidermis. In the deep dermis, by the side of ulceration, there were caseating tuberculous granulomas along with perivascular infiltrate with vessel wall thickening and endothelial cell swelling. Fite stain for AFB was negative. These features were consistent with papulonecrotic tuberculide. AFB culture of biopsy specimen was negative. Repeated courses of antibiotic therapy did not yield desired results; hence, antitubercular therapy was initiated keeping in mind the possibility of papuloneurotic tuberculide of the penis. Four-drug combination therapy of rifampicin, isoniazid, pyrazinamide, and ethambutol was given for initial 2 months followed by combination of rifampicin and isoniazid to complete total 6 months of standard antitubercular therapy. The lesions started responding to therapy in next two weeks and complete healing with residual depressed scars occurred after three months of therapy (Fig. 2). Fig. 2 Healing with residual depressed scars after 3 months of therapy Tuberculosis of the penis is rare, even in third world countries where the prevalence of tuberculosis remains relatively high.1 Till 1999, only 161 cases of penile tuberculosis were reported.2 Understandably, papulonecrotic tuberculide involving the glans penis is even rarer.3,4 Tuberculides are hypersensitivity reactions to Mycobacterium tuberculosis or its products in individuals with good immunity.5 These cases are characterized by positive tuberculin test, evidence of present or past tuberculosis, absence of M. tuberculosis in the skin lesions and response to antitubercular treatment.5 However, a focus of tuberculosis elsewhere in the body may not be demonstrable in majority of the cases with papulonecrotic tuberculide as in our case.2,6 Papulonecrotic tuberculides are characterized by recurrent eruptions of asymptomatic, dusky red papules, which ulcerate and crust, and heal after a few weeks with varioliform scarring.5,7 These occur symmetrically and predominantly on the extensor aspects (legs, knees, elbows, hands and feet) of the extremities. Other areas that may be rarely affected by papulonecrotic tuberculides are the ears, face, buttocks, perniotic areas and penis.5 In Japan, penile tuberculide has been considered a disease entity.4 Thus, it is important to remember tuberculosis as an underlying cause of penile ulcers, more so in countries like India where prevalence of tuberculosis is still high.

Nodular granulomatous phlebitis: An uncommon tuberculid

The tuberculids constitute the immune-mediated non-infectious cutaneous hypersensitivity reaction pattern to the underlying focus of Mycobacterium tuberculosis antigen in patients with good cell-mediated immunity. Papulonecrotic tuberculid (PNT) is a true tuberculid that usually occurs secondary to the underlying focus of infection which may be in the lymph nodes, lungs, bone, or rarely in other systems. It manifests as asymptomatic symmetric eruptions of erythematous papules with central areas of ulceration and crusting that heals with varioliform scars. PNT presenting as a generalized folliculitis-like lesion and rosettes has not been described earlier. Furthermore, PNT occurring as a hypersensitivity response due to underlying mediastinal tuberculous lymphadenitis (MTL) is rare. We are highlighting a case of PNT secondary to the MTL in a middle-aged woman.

Papulonecrotic tuberculid (PNT), a form of cutaneous tuberculosis (TB), is uncommon in children. We identified eight children (six girls and two boys) with PNT. Their ages ranged from 19 to 139 months (median 47.5 months, mean:64.75 months). Skin lesions had been present for 2-24 weeks (median: 4 weeks) before diagnosis. All patients displayed scattered papulo- and/or pustulonecrotic lesions on the limbs, and the ears were involved in six patients. Lesions healed with varioliform scars. Associated pulmonary TB was present in seven patients. Additional clinical findings included fever (n = 4), hepatomegaly (n = 4), lymphadenopathy (n = 3), phlyctenular conjunctivitis (n = 3), and splenomegaly (n = 2). Histology of eight biopsies showed ulceration (n = 6), dermal necrosis (n = 6) (follicle-centered in two), granulomatous inflammation (n = 6) (palisading granuloma-like in three), superficial and deep infiltrate of lymphocytes (n = 7), erythrocyte extravasation (n = 7), and subepidermal edema (n = 3). Vasculitis was not a feature. A Ziehl-Neelsen stain was negative in all. Glycosaminoglycans were not increased. Immunohistochemistry found a predominance of T lymphocytes, macrophages, a few antigen-presenting cells, and no B lymphocytes, consistent with a type IV hypersensitivity reaction. Polymerase chain reaction (PCR) performed on deparaffinized tissue identified M. tuberculosis DNA in one biopsy. All patients received combination anti-TB treatment for 6 months. Six patients were compliant and were followed up for 6-30 months. Skin lesions and pulmonary TB healed in all. PNT in children resembles the adult form, but phlyctenular conjunctivitis and associated TB are more common, scrofuloderma and concomitant erythema induratum of Bazin are unusual, and vasculitis is not found. In cases where M. tuberculosis DNA can be confirmed with PCR, papulonecrotic TB is perhaps the more appropriate nomenclature.

A 40 years old male patient of poor socioeconomic condition presented with a well circumscribed rough surfaced and fissured, verrucous plaque on left axilla and a similar lesion on right foot- which were clinically diagnosed as tuberculosis verrucosa cutis. He also had necrotic papular eruption with varioliform scarring in some lesions on upper back clinically diagnosed as papulonecrotic tuberculid. He had fever and cough and mild weight loss suspicious of pulmonary tuberculosis. On investigation ESR was raised, mild anaemia was present, MT was strongly positive, chest x-ray was suggestive of tuberculosis. So, he was diagnosed as a case of simultaneous occurrence of tuberculosis verrucosa cutis (TVC) with papulonecrotic tuberculid (PNT) with pulmonary tuberculosis (PTB). Standard anti tuberculosis chemotherapy already started to offer cure of all lesions.

Hypersensitivity reactions to Mycobacterium tuberculosis (tuberculids) include papulonecrotic tuberculid (PNT), erythema induratum (EI), and lichen scrofulosorum. . These rarely coexist in a child. We, therefore, report coexistence of papulonecrotic tuberculid and erythema induratum in a four-year old male. He presented with two-week history of skin eruptions involving the arm, abdomen and ears. Reddish bumps later appeared on the legs. Examination revealed erythematous papules, with central necrosis, on the lateral aspect of the left upper arm, ear helices and trunk. There were also several symmetrically distributed non-tender erythematous nodules, some with necrosis, on the shins and calves. Histology of the biopsied papules (PNT) revealed intense wedge-shaped necrosis with perivascular inflammation.and of the leg nodule (EI), extensive dermal fat necrosis with granulomatous lymphocytic infiltration. These findings are compatible with TB. Chest-xray revealed hilar and paratracheal adenopathy. Sputum was positive for Mycobacterium tuberculosis DNA using polymerase chain reaction (PCR). He did well on anti-tuberculosis medications. erythema induratum (EI), and lichen scrofulosorum. . These rarely coexist in a child. We therefore report coexistence of papulonecrotic tuberculid and erythema induratum in a four-year old male. He presented with two-week history of skin eruptions involving the arm, abdomen and ears. Reddish bumps later appeared on the legs. Examination revealed erythematous papules, with central necrosis, on the lateral aspect of the left upper arm, ear helices and trunk. There were also several symmetrically distributed non-tender erythematous nodules, some with necrosis, on the shins and calves. Histology of the biopsied papules (PNT) revealed intense wedge-shaped necrosis with perivascular inflammation.and of leg nodule (EI) extensive dermal fat necrosis with granulomatous lymphocytic infiltration. These findings are compatible with TB. Chest-xray revealed hilar and paratracheal adenopathy. Sputum was positive for Mycobacterium tuberculosis DNA using polymerase chain reaction (PCR). He did well on anti-tuberculosis medications.

Lichen scrofulosorum in a Saudi adolescent with multifocal tuberculosis

Tuberculids are rarely associated with male genital tract tuberculosis (TB). Tuberculous epididymo-orchitis (TBEO) has been associated rarely with papulonecrotic tuberculid (PNT) but not with erythema induratum (EI) or the simultaneous occurrence of different tuberculids. A retrospective assessment of tuberculids that occurred with underlying TBEO was carried out. Five patients, four with one and one with two skin biopsies, with clinical diagnoses of PNT (two), EI (one), impetigo (two) and calf ulcer (one), formed the study cohort. Histopathological evaluation confirmed PNT and EI in four and two skin biopsies, respectively. Two patients who returned for follow-up were commenced on anti-tuberculous therapy. All patients sought medical attention 3-34 months later for tender right-sided (two) and left-sided (three) testicular masses. Orchidectomy was undertaken following a poor clinical response to empirical treatment with trimethoprim sulfamethoxazole. Pathological examination of the testis and epididymis confirmed TBEO. The patients were initiated on anti-tuberculous therapy. There was dramatic healing of the skin lesions. Tuberculids are a sentinel cutaneous manifestation of visceral TB and a valuable external audit of treatment compliance and response. Heightened recognition of and more rigorous genitourinary tract investigation are necessary to identify occult or asymptomatic TBEO as the underlying cause of tuberculids.

The purpose of the present study was to assess imaging findings of primary immunoglobulin G4 (IgG4)-related cervical lymphadenopathy. Five consecutive patients with clinically, serologically, and histopathologically confirmed primary IgG4-related cervical lymphadenopathy without any other organ involvement were included. All patients underwent contrast-enhanced computed tomography (CT), and four underwent 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT. We retrospectively reviewed the images and assessed the number, size, location, central necrosis, perinodal infiltration, penetrating vessels, and maximum standardized uptake values (SUVmax) of the enlarged cervical nodes. Thirteen enlarged cervical nodes measuring larger than 10mm in minimum diameter were identified. The maximum and minimum diameter of enlarged nodes ranged from 1.2 to 3.2cm (median, 1.8cm) and from 1.0 to 1.9cm (median, 1.2cm), respectively. Lymphadenopathy was unilateral in all patients, and eight enlarged nodes were located at level IB (62%), one at level II (8%), three at level IV (23%), and one at level V (8%). Central necrosis was not seen in any nodes. Perinodal infiltration was seen in only one node (8%), and penetrating vessels were seen in seven nodes (54%). The median SUVmax of nine nodes was 4.45 (range, 2.08-12.44). Eight enlarged nodes (62%) were located in the submandibular region. Central necrosis was not observed in any nodes and perinodal infiltration was observed in one node (8%).

The incidence of tuberculosis and extrapulmonary forms of this disease is increasing all over the world. Lupus vulgaris is the most prevalent form of cutaneous tuberculosis in Europe and the Middle East. Papulonecrotic tuberculid, the most common form of hyperergic response to mycobacteria or their fragments, is uncommon in children. We report lupus vulgaris with papulonecrotic tuberculid in a 12-year-old girl who had a 3-year history of slowly growing plaques on her trunk, extremities, and the tip of her nose and papuloulcerative lesions over her entire body. A skin biopsy specimen showed minimally caseating granulomatous inflammation. Staining for acid-fast bacilli was negative in both plaques and papules. Polymerase chain reaction identified Mycobacterium tuberculosis DNA in the patient's sputum, gastric fluid, and plaques and was negative in the papules. She was started on antituberculous therapy with four drugs and her lesions responded rapidly.

SummaryBackgroundNo randomised controlled trial (RCT) has previously evaluated the effect of antitubercular therapy (ATT) in patients with uveitis of undetermined cause who tested positive on interferon-gamma release assays (IGRA), despite the absence of other identifiable causes of uveitis. We aimed to assess the efficacy and safety of treatment involving ATT compared to treatment without ATT in these patients, with respect to uveitis resolution and reduction in the risk of relapse.MethodsWe conducted a single-blind, single-centre, phase 2 RCT at the uveitis clinic of Cipto Mangunkusumo Hospital in Jakarta, Indonesia, from August 16, 2021, to February 5, 2024. Seventy-six adults with newly diagnosed, active uveitis of undetermined cause and a positive IGRA were randomised 1:1 using block randomisation (block size 4) into two groups. Participants in the ATT group received an additional full course of ATT in addition to systemic corticosteroids. The control group received systemic corticosteroids without ATT. Investigators were masked to group assignment. The primary endpoint was the complete resolution of uveitis six months after randomisation. The trial is registered at ClinicalTrials.gov (NCT05005637).FindingsSeventy-six participants were randomly assigned to either ATT (n = 37) or control (n = 39) group. At primary end point, more participants assigned to the ATT group achieved the primary outcome of complete uveitis resolution compared to the control group (30/37, 81.1% vs. 20/39 participants; 51.3%, relative risk [RR] 1.58, 95% CI 1.12–2.23, p = 0.0060). Over the subsequent follow-up period, complete uveitis resolution was observed in 34 and 24 participants assigned to the ATT and the control groups, respectively. Additionally, uveitis relapse occurred in fewer participants assigned to the ATT group compared to those assigned to the control group (2/34 participants, 5.9% vs. 7/24 participants, 29.2%; HR 0.20, 95% CI 0.05–0.89, p = 0.0210). The findings regarding uveitis resolution and relapse rates were consistent in the per-protocol analysis.InterpretationIn IGRA-positive patients with uveitis of undetermined cause, initial treatment with ATT resulted in a significant benefit over those not receiving ATT.FundingThis work was supported by RISPRO-10.13039/501100014538LPDP (Riset Inovatif Produktif—Lembaga Pengelola Dana Pendidikan).