Congenital Tuberculosis Manifesting as Cutaneous Disease

Tuberculosis continues to plague the world despite major advances in chemotherapy. Perinatally acquired tuberculosis is uncommon. Cutaneous manifestations in perinatal tuberculosis are exceedingly rare, and a review of literature has revealed only five such reported cases. 1–3 We report here a neonate who presented with cutaneous manifestations of congenital tuberculosis. Case report. A 12-day-old term male baby born to a primigravida, unsupervised mother was admitted with complaints of fever and poor feeding since Day 3 of life. Cutaneous lesions on the face were observed 4 days before admission. These lesions started as maculopapular erythematous eruptions which progressed to form a vesicle and subsequently broke down to form a punched out ulcer. The baby had a weight of 1.9 kg, length of 45.0 cm and occipitofrontal circumference of 30 cm. There was no pallor, icterus or lymphadenopathy. Apart from depressed neonatal reflexes, the examination was unremarkable. There were two deeply punched out ulcers on the face (Fig. 1). One was situated in the temporal region and the second was infraorbital below the lateral canthus of the eye. These were ∼5 to 6 mm in diameter. The margins were clear and there was no discharge.Fig. 1: Papulonecrotic tuberculids on the face.Investigations revealed a hemoglobin of 15.5 g/dl; total leukocyte count of 7.2 × 10 9 /l; neutrophils 68, lymphocytes 25, monocytes 5, and eosinophils 2; absolute neutrophil count of 4.8 × 10 9 /l; and a platelet count of 290 × 10 9 /l. Blood culture was sterile. A swab taken from skin lesion was negative for bacteria and acid-fast bacilli (AFB). The chest radiograph was normal. Cerebrospinal fluid analysis showed 10 cells/mm 3, all of which were polymorphonuclear cells. The biochemical analysis of cerebrospinal fluid was normal, and the culture was sterile. Serologies for syphilis and human immunodeficiency virus were negative. Initially the child was considered to have septicemia and treatment was started with cefotaxime and gentamicin. Multiple new lesions erupted on the face and scalp. A review of the history revealed that the mother had had low grade fever and cough since the fourth month of gestation. Investigations confirmed that she had pulmonary tuberculosis. Her sputum smear showed numerous AFB. The baby was then investigated for tuberculosis. A fine needle aspiration cytology from the new lesions showed presence of acute inflammatory cells. No granulomas or epithelioid cells were seen. After this, tissue from a biopsy of the lesion was processed by polymerase chain reaction for Mycobacterium tuberculosis (by S. Arora) and was strongly positive. A diagnosis of congenital cutaneous tuberculosis was made, and the baby was given antitubercular therapy (rifampin, isoniazid and pyrazinamide for 2 months, followed by rifampin and isoniazid for 7 months). He has now received drugs for 4 months. The lesions have healed completely, and there has been steady weight gain. The mother is also receiving antitubercular therapy (rifampin, isoniazid, ethambutol and pyrazinamide for 2 months followed by rifampin and isoniazid for 4 months) and is presently asymptomatic. Her sputum is now negative for AFB. The initial sputum culture grew M. tuberculosis. Discussion. The criteria for making a diagnosis of congenital tuberculosis were defined by Bietzke in 1935. 4 These include (1) bacteriologic proof, (2) evidence of disease within the first few days of life, (3) a primary complex in the liver and (4) exclusion of extrauterine transmission. These criteria are difficult to fulfil, as they require separation of baby from the mother and an open liver biopsy. Fetal infection occurs by hematogenous spread or fetal aspiration of infected amniotic fluid by the fetus. 5 The clinical manifestations of congenital tuberculosis are neither distinctive nor pathognomonic. Meningitis, jaundice, papular or pustular skin lesions and otitis media have been documented as rare manifestations. 6 In cutaneous tuberculosis the infection may occur by the exogenous route, autoinoculation or by the endogenous route (Table 1). 7, 8 A hematogenous (endogenous) route of infection is likely in the propositus, in whom the nature of the skin lesions was typical of the papulonecrotic variety of tuberculids. Formation of a tuberculid represents a type III hypersensitivity reaction to mycobacteria. The fine needle aspiration, in the index case, showed polymorphonuclear cells and no evidence of granuloma formation. In the early stages tuberculids often show polymorphonuclear cells. Granuloma formation and scarring are later events.Table 1: Classification of cutaneous tuberculosis*Detection of AFB by microscopy needs at least 5 × 10 3 to 1 × 10 4 organisms per ml of sputum. In tuberculids failure to demonstrate mycobacteria in histologic sections has been ascribed to the small number of organisms in the lesion. The recently developed technique of deoxyribonucleic acid amplification by PCR is considered a reliable method for detection of M. tuberculosis. Although the sensitivity and specificity of PCR are variable, well-standardized PCR is a useful method for the diagnosis of tuberculosis when used in conjunction with clinical criteria. 9, 10 The positive PCR when coupled with the evidence of maternal infection and the response to antitubercular therapy confirm a diagnosis of tuberculosis in the index case. Diagnosis of congenital tuberculosis requires a very high index of suspicion. The Beitzke criteria are not practically applicable in present day clinical practice. Investigators now believe that only one of the following criteria is sufficient to diagnose congenital tuberculosis in patients with proven tuberculous lesions 11 : (1) lesions appearing in the first week of life; (2) a primary hepatic complex or caseating hepatic granuloma; (3) tuberculous infection of the placenta or the maternal genital tract; or (4) exclusion of all possible sources of postnatal transmission. The index case developed symptoms at Day 3 of life, suggesting that the tuberculous infection was acquired in utero. The case illustrates the need for careful evaluation of the mother when analyzing illnesses in a neonate. Failure to do this initially, and the rare cutaneous involvement, led to some delay in establishing the diagnosis. Fortunately tuberculous infection was suspected before complications ensued. Institution of antitubercular therapy proved curative.