Presumed Levofloxacin-associated Lichenoid Drug Eruption in a Child With Rifampicin-resistant Tuberculosis

To the Editors: A 21-month-old HIV-uninfected female child was evaluated as a household contact of an individual with confirmed rifampicin-monoresistant tuberculosis. She presented with a 2-week history of cough, night sweats and poor growth. The rest of her medical and dermatological history was unremarkable and her clinical, including dermatologic, examination was normal. Chest x-ray showed uncomplicated hilar lymphadenopathy, tuberculin skin test was positive and gastric aspirates were Xpert MTB/RIF Ultra (Cepheid Inc, Sunnyvale, CA) negative. Based on these results, and the household exposure to rifampicin-resistant tuberculosis (RR-TB), she was clinically diagnosed with nonsevere RR-TB and initiated on bedaquiline, linezolid, levofloxacin, terizidone and clofazimine. After 3 weeks of treatment, the child’s mother noted a generalized pruritic rash that significantly impacted the child’s sleep and daily activities. The child was otherwise well and was not exposed to any other medications than her RR-TB treatment. On examination, she was content, playful and systemically well. A widespread, photodistributed rash with significant involvement of the face and extremities was noted (Fig. 1A) The rash was characterized by erythematous, scaly papules and plaques involving the face and upper and lower limbs with more established lesions displaying a purple–gray hue. The mucosae, palms and soles were unaffected.FIGURE 1.: A: A widespread symmetrical rash with significant involvement of the face and the extremities, displaying a photo distribution. Erythematous papules and plaques seen with lesions displaying a purple, gray hue. Areas with some scaling noted. B: Hematoxylin and eosin section of the skin with superficial and deep perivascular inflammation (pink arrows). C: The occasional eosinophils (blue circles) and deeper inflammatory infiltrate were clues in support of a drug reaction.A dermatologist diagnosed a lichenoid drug eruption (LDE), with differential diagnoses of lichen planus or viral exanthem. Histology revealed a lichenoid interface dermatitis with superficial and deep perivascular inflammation comprising lymphocytes, plasma cells and occasional eosinophils (Fig. 1B). The presence of occasional eosinophils and a deeper infiltrate supported the diagnosis of an LDE (Fig. 1C). Levofloxacin was stopped due to its known association with cutaneous adverse drug reactions and a potent topical steroid, clobetasol propionate, was initiated. The rash improved significantly and the steroid was discontinued after one week without weaning. The skin continued to improve leaving postinflammatory hyperpigmentation, primarily on the face. Two weeks after discontinuing levofloxacin it was reintroduced and the rechallenge was uneventful. No recurrence of the rash was noted after 5 weeks. To our knowledge, this is the first report of presumed levofloxacin-associated LDE in a young child being treated for RR-TB. LDE usually has a delayed onset after drug exposure and typically presents with pruritic, symmetrical eruptions resembling lichen planus. Diagnosis is based on history, clinical presentation, histopathology and improvement upon drug withdrawal.1,2 Fluoroquinolones are highly bactericidal against Mycobacterium tuberculosis and remain an essential part of RR-TB regimens. However, they are also notorious for their association with cutaneous hypersensitivity reactions, including phototoxicity.3,4 In favor of LDE in our patient is a known drug exposure history, lichenoid skin morphology with a predilection for photodistributed areas and supportive histology showing a lichenoid interface with eosinophils. In addition, the rash improved with drug interruption. The child was assessed to have a Probable Adverse Drug Reaction according to the Naranjo Adverse Drug Reaction Probability Scale. Given the importance of fluoroquinolones in treating RR-TB, rechallenging levofloxacin was necessary and successful. This case highlights the need to differentiate between cutaneous reactions that can be managed through treatment or rechallenged from those requiring drug discontinuation and allergy labeling.5