Erythema nodosum as a rare presentation of pulmonary tuberculosis in adolescents: A case report

Abstract

Aim and background

Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex, is a multisystemic infectious disease with variable clinical manifestations. Pulmonary involvement is the most common presentation, whereas cutaneous manifestations are rare. Early diagnosis and timely treatment are essential to prevent organ damage, reduce long-term sequelae, and minimize psychosocial impact, particularly in children and adolescents. This case highlights the importance of maintaining a high index of suspicion for TB, even in atypical presentations such as dermatologic findings, especially in high-endemicity settings.

Case description

We report the case of an 11-year-old female with confirmed active pulmonary TB who presented with tender nodular lesions on the lower limbs. The diagnosis was established based on clinical, microbiological, immunological, and radiological criteria.

Conclusion

A comprehensive clinical approach—integrating detailed history-taking, targeted diagnostic workup, and multidisciplinary evaluation—is key to ensuring treatment success and reducing complications in high-burden diseases like tuberculosis.

Clinical significance

Erythema nodosum is a rare initial manifestation of TB in children and adolescents, with limited cases reported in the literature.

1. Introduction

Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex, remains a major global public health concern, affecting approximately 1.1 million children annually. Pediatric TB accounts for 12% of global TB morbidity, with a lower incidence than in adults but disproportionately higher mortality. The cumulative case-fatality rate is estimated at 21.9%, with the greatest impact among children aged 0–4 years (43.6%), compared to 14.9% in those aged 5–14 years, underscoring the urgency of early detection and intervention [[1], [2], [3], [4]].

TB transmission is strongly influenced by social determinants of health, which exacerbate disparities in vulnerable populations, including migrants and socioeconomically disadvantaged groups, through increased environmental exposure and reduced access to healthcare [5]. Clinically, TB is a multisystemic disease, though pulmonary involvement remains the predominant form. Its broad clinical spectrum—combined with the challenges of microbiological confirmation in children—necessitates a thorough and integrative diagnostic approach to reduce long-term complications such as impaired lung function [[6], [7], [8]].

Erythema nodosum, the most common panniculitis in children, is a rare dermatologic condition in the pediatric population. It presents with painful, erythematous-to-violaceous subcutaneous nodules, typically on the lower limbs. Pathophysiologically, it represents a neutrophilic septal panniculitis without vasculitis, attributed to immune complex deposition in the subcutaneous fat [9]. Systemic symptoms such as arthralgia, fever, and malaise may accompany the skin lesions. Although associated with various infections (e.g., Epstein-Barr virus, Streptococcus pyogenes), medications, malignancies, and chronic inflammatory diseases, most cases remain idiopathic [9,10].

We present the case of an adolescent girl with active pulmonary tuberculosis, whose initial manifestation was erythema nodosum—a rare and often overlooked presentation that warrants high clinical suspicion in endemic areas.

2. Case description

An 11-year-old Venezuelan girl residing in Colombia for the past 10 years, living in an urban area and attending school regularly, presented with a one-month history of dry cough and clear rhinorrhea. Two weeks prior to admission, she developed pruritic, erythematous nodular lesions on the lower limbs, accompanied by right knee pain that began one week earlier. She reported no additional symptoms. Initial evaluation at a local healthcare center led to outpatient management with oral prednisolone for 5 days; however, due to persistence of the lesions and worsening pain, she was referred to a tertiary care hospital.

Her personal and perinatal history was unremarkable. There was no relevant family history except for close contact with a grandmother who had chronic unexplained cough. Her immunization schedule was complete, and dietary assessment via food diary revealed an adequate nutritional intake. There was no history of exposure to toxic substances.

On physical examination, she was in good general condition with normal anthropometric indices (Body mass index, BMI-for-age Z-score: −1.29). Dermatologic evaluation revealed bilateral, symmetric, poorly defined erythematous nodular lesions on the lower limbs, measuring approximately 2 cm in diameter, firm and tender on palpation, with surrounding erythema and warmth; some lesions showed violaceous discoloration (Fig. 1).

Fig. 1.

Erythematous subcutaneous nodules on the lower limbs, consistent with erythema nodosum.

She was admitted for pain management with dipyrone and underwent further diagnostic workup. Urinalysis revealed microscopic hematuria with eumorphic red blood cells (25.9/μL), while renal function tests (creatinine and Blood Urea Nitrogen, BUN) were within normal limits. Renal ultrasound showed no abnormalities. Complete blood count was normal for age, with no evidence of anemia, leukocytosis, or thrombocytopenia. Serologies for HIV, syphilis, hepatitis B, Epstein-Barr virus, and cytomegalovirus were negative. A tuberculin skin test (TST/PPD) showed 20 mm of induration, raising suspicion of tuberculosis.

The chest radiograph was initially interpreted as normal; however, upon further review, it showed findings suggestive of left hilar lymphadenopathy. A chest CT scan revealed multiple apical granulomatous lesions in the left lung, coalescing into a large plaque measuring 59 × 41 mm, consistent with a granulomatous pattern. (Fig. 2, Fig. 3). Bronchoscopy with bronchoalveolar lavage (BAL) was performed, yielding negative Gram stain and potassium hydroxide (KOH) preparation; however, despite negative stains, molecular detection of Mycobacterium tuberculosis complex by polymerase chain reaction (PCR) was positive, thereby confirming the diagnosis of active pulmonary tuberculosis according to clinical, radiologic, immunologic, and microbiologic criteria.

Fig. 2.

Chest X-ray showing findings suggestive of left hilar lymphadenopathy.

Fig. 3.

Chest CT scan revealing left apical granulomatous lesions forming a plaque measuring 59 × 41 mm.

Additional differential diagnoses, including rheumatologic disorders, were ruled out by the pediatric rheumatology team. Antinuclear antibodies (ANA) were positive at a titer of 1:80 with a fine granular nuclear pattern, which was considered non-specific in this clinical context. Dermatology assessment led to a skin biopsy of the nodular lesions (Fig. 4). Although erythema nodosum is typically a clinical diagnosis, a skin biopsy was performed due to diagnostic uncertainty and to exclude other causes of panniculitis. During hospitalization, the patient received multidisciplinary care including nutritional, psychological, and social work support.

Fig. 4.

Skin biopsy demonstrating mild superficial perivascular lymphocytic dermatitis without epidermal damage.

Following initiation of standard anti-tuberculosis therapy—consisting of a two-month intensive phase with rifampin, isoniazid, pyrazinamide, and ethambutol, followed by a four-month continuation phase with rifampin and isoniazid—under the supervision of pediatric infectious disease and pulmonology specialists, the patient showed progressive improvement. She was discharged asymptomatic after 12 days of hospitalization and continued the treatment regimen at home under close medical follow-up.

Written informed consent was obtained from the patient's legal guardian for publication of this case report and accompanying images.

3. Discussion

Tuberculosis remains a major global health challenge. In 2019, an estimated 997,500 pediatric TB cases were reported worldwide, with lower detection rates in children aged 0–4 years (41%) compared to those aged 5–14 years (63%). In 2023, TB showed a mortality rate of 2.1 per 100,000 population, surpassing the mortality rates of both COVID-19 and HIV in the pediatric population. That year, an estimated 1.3 million children globally were living with tuberculosis [11,12].

In Colombia, the burden of pediatric TB is similarly concerning. Between 2010 and 2018, a total of 260 TB-related deaths were recorded in children under 15 years of age [13]. These data highlight the urgent need for early detection strategies to prevent long-term consequences at the individual, familial, and societal levels [14]. In the present case, early diagnosis helped to avoid acute complications, mitigate functional and social impact, and facilitate timely discharge.

Erythema nodosum (EN) is a self-limiting dermatologic condition characterized by painful, non-ulcerative, raised erythematous nodules, typically located on the lower extremities. Histologically, it corresponds to septal panniculitis, often with radial granulomas, although fat necrosis and vasculitis may occasionally be observed [15].

Although up to 55% of erythema nodosum cases are idiopathic, several etiologic associations have been described in the literature. In pediatric populations, the most frequent identifiable cause is streptococcal pharyngitis (up to 48% of cases), followed by systemic conditions such as sarcoidosis (11–25%) and inflammatory bowel disease, particularly during pregnancy (2–5%) [16,17].

Erythema nodosum has also been reported as a cutaneous manifestation of tuberculosis infection. In this context, it is sometimes referred to as erythema induratum of Bazin to distinguish it from other forms of nodular vasculitis. Its prevalence in TB patients varies geographically, with studies from Asia and South Korea reporting rates around 20% [16]. For instance, a study by Chen et al. (2013) found that 30.4% of 107 patients with erythema nodosum tested positive for tuberculosis [18], while Kim et al. (2018) reported a striking 87.5% prevalence of TB among 14 patients diagnosed with erythema nodosum [15]. Notably, no studies from Latin America have specifically investigated this clinical association.

The occurrence of tuberculosis with cutaneous manifestations such as erythema nodosum poses a diagnostic challenge for healthcare providers. Nonetheless, this possibility should always be considered in endemic regions or among high-risk populations—including individuals with known exposure, migrant communities, or those living in overcrowded conditions [16,17]. Limited clinical training in dermatologic diagnosis can hinder appropriate evaluation, but access to dermatology consultation allows for a more comprehensive and accurate diagnostic process, as exemplified in the present case.

Several authors have suggested screening for tuberculosis in patients presenting with erythema nodosum. However, reports describing this association in the literature remain scarce [16,17], and published cases are limited to adult women aged 22 and 59 years, respectively. In pediatric populations, only two cases have been documented to date. The first, described by Rodrigues et al., in 2022, involved a 9-year-old girl who was started on anti-TB treatment after exclusion of other systemic causes and based on a positive tuberculin skin test (TST) and interferon-gamma release assay (IGRA), although without microbiological confirmation [19]. The second case, reported by Sulakshi et al. that same year, involved an 8-year-old girl treated for presumed TB based on the presence of erythema nodosum, a history of close contact, and a positive TST—again, in the absence of microbiological confirmation [20].

In the present case, dermatologic lesions were the first clinical sign that prompted a tuberculin skin test (TST/PPD), triggering the diagnostic workup that led to confirmation of tuberculosis. Although the PPD test has limited specificity and predictive value—especially in children and adolescents—it remains the most widely used immunological tool worldwide for detecting latent TB infection and guiding clinical suspicion. It is still included in many diagnostic protocols, including those used in Colombia. However, the absence of a definitive gold standard for TB infection continues to limit optimal case identification [21].

In addition to the immunological (positive PPD) and clinical (erythema nodosum) findings—and although the patient had a persistent cough for more than two weeks, this was not the reason for consultation—radiological imaging played a decisive role. Despite initial chest radiographic findings suggestive of left hilar lymphadenopathy, chest CT revealed apical granulomatous lesions, highlighting a well-documented limitation of radiography in pediatric TB. Computed tomography has been shown to be superior in detecting characteristic findings such as lymphadenopathy and parenchymal lesions in children [22,23], both of which were present in this case.

Molecular testing via polymerase chain reaction (PCR) provided definitive microbiological confirmation, proving crucial in this atypical presentation. Rapid detection of Mycobacterium tuberculosis using PCR in bronchoalveolar lavage (BAL) samples significantly enhanced diagnostic accuracy and allowed for timely initiation of therapy [24]. Together, the clinical, radiologic, immunologic, and microbiological evidence confirmed the diagnosis of active pulmonary TB.

An important aspect of this case is the diagnostic challenge posed by the initial presentation. Although erythema nodosum is a recognized manifestation associated with tuberculosis, it rarely constitutes the predominant or initial clinical feature in pediatric patients, particularly in the context of subtle findings on initial chest radiography. In this case, dermatologic findings prompted further investigation, ultimately leading to the diagnosis of active pulmonary tuberculosis.

This highlights the importance of maintaining a high index of suspicion for tuberculosis in children presenting with atypical dermatologic manifestations, especially in endemic regions, in order to avoid diagnostic delays and ensure timely and appropriate management.

4. Conclusion

Erythema nodosum as a presenting feature of active tuberculosis in children and adolescents is rare. This case emphasizes the importance of maintaining a high index of clinical suspicion and initiating an appropriate diagnostic algorithm when pediatric patients present with this dermatologic manifestation, particularly in TB-endemic regions. Early identification allows for timely treatment and prevents complications associated with delayed diagnosis.

CRediT authorship contribution statement

Harold Escudero-Quintero: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Software, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization. Diana Marcela Mosquera-Romero: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Software, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization. Juliana Taborda-Merchán: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Software, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization.

Clinical significance

This case highlights the importance of considering tuberculosis in children presenting with atypical dermatologic manifestations such as erythema nodosum, particularly in endemic regions, to avoid diagnostic delays and ensure timely and appropriate management.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

List of abbreviations:

TB

Tuberculosis

BMI

Body Mass Index

BUN

Blood Urea Nitrogen

HIV

Human Immunodeficiency Virus

CT

Computed Tomography

KOH

Potassium Hydroxide;

ANA

Antinuclear Antibody

IGRA

Interferon-Gamma Release Assay

PPD/TST

Purified Protein Derivative/Tuberculin Skin Test

PCR

Polymerase Chain Reaction

Appendix A. Supplementary data

The following is the Supplementary data to this article: