Lichenoid Drug Eruption Progressing into Erythroderma in A Case of Cervical Scrofuloderma Due to Multi Drug-Resistant Tuberculosis.

Sir,

Lichenoid drug eruption (LDE) due to first-line anti-tubercular therapy (ATT) (Ethambutol, Isoniazid, p-Aminosalicylic acid, and Streptomycin) is known,[1] however, it occurs rarely after second-line ATT with the implicated drug in the literature being Cycloserine.[23] Here, we describe a case of LDE due to second-line ATT which progressed into erythroderma.

A 29-year-old female was on a second-line ATT regimen (Linezolid, Bedaquiline, Clofazimine, Cycloserine, Moxifloxacin) for 4 months for cervical scrofuloderma, presented with itchy red raised lesions all over her body. On general examination, she had a pedal, upper limb, right breast edema. The cutaneous examination [Figure 1] revealed diffuse cutaneous erythema and generalized violaceous papules, plaques. There were crusted erosions on the lower part of the neck and upper part of the chest. Scaling was present on the palms, soles, scalp with diffuse hair loss, and a positive hair pull test. She had fissuring on the tongue and lips. Rest mucosae were normal. The nails [Figure 2] showed transverse brown lines, onychomadesis of all 20 nails, and subungual hyperkeratosis of all toenails. The laboratory investigations were normal except for increased blood eosinophil counts (7%). Histopathology revealed hypergranulosis, irregular acanthosis, spongiosis, vacuolar degeneration of the basal layer with melanin incontinence, and melanophages in the superficial dermis. The dermo-epidermal junction had chronic inflammatory cell infiltrate and a few eosinophils [Figures 3 and 4]. These clinical and histopathological findings suggested a diagnosis of LDE that was progressing into erythroderma. The Naranjo score was 8 suggesting a probable relationship between the drug and cutaneous eruption. We speculate that the triggering drug was Cycloserine. It being the only second-line ATT drug reported to cause LDE.[23] Hence, the ATT drugs were stopped and systemic steroids in a tapering dose were administered following which the erythema, edema, and scaling subsided. The violaceous papules and plaques started resolving with post-inflammatory hyperpigmentation. But the restart of ATT led to an increase in the violaceous papules and plaques [Figure 2].

Figure 1

Generalized cutaneous erythema, crusted erosions on the lower part of the neck and upper chest, pedal edema, edema over the right breast.

Figure 2

Onychomadesis, transverse brown lines, and brown discoloration involving all the fingernails. Multiple violaceous papules and plaques on the thighs.

Figure 3

The epidermis shows hypergranulosis, irregular acanthosis, spongiosis, vacuolar degeneration of the basal layer, and chronic inflammatory cell infiltrate at the dermo-epidermal junction (H&E X100).

Figure 4

Vacuolar degeneration of the basal layer, melanin incontinence in the superficial dermis, and an eosinophil (H&E X400).

There is a paucity of reports of LDE caused by second-line ATT except for a few with Cycloserine. The average latent period for LDE is 2–3 months.[4] Rarely do cases progress into erythroderma. The oral provocation test (OPT) is the gold standard for the confirmation of drug causality.[4] In vivo and in vitro tests and scoring systems that help in establishing drug causality are enlisted in Tables 1 and 2.[45]

Table 1

Tests for establishing the drug causality[4]

In vivo tests	In vivo tests
Prick and intradermal testing	Histamine release test
Patch testing	Basophil degranulation test
Dechallenge and rechallenge	Passive hemagglutination test
	Leukocyte and macrophage migration inhibition factor tests
	Lymphocyte transformation test
	Lymphocyte toxicity test

*In vitro tests are safer but are difficult to do whereas in vivo tests are easier to do but the safety of these tests, especially in cases of severe cutaneous adverse drug reactions (CADR), remains an issue[4]

Table 2

Scoring systems for causality assessment[5]

Naranjo adverse drug reaction probability scale

WHO-UMC (World Health Organization-Uppsala Monitoring Center) causality assessment

Kramer’s algorithm

Roussel Uclaf causality assessment method

In our case clinical examination, histopathology helped in the diagnosis of LDE which was further supported by the Naranjo score and reappearance of lesions after re-starting ATT. As all 5- second-line ATT drugs were reintroduced in a short span of 2 weeks by Respiratory Physicians, the exact causative drug could not be found out. Sequential re-introduction could be of help in such circumstances to find out the exact implicated drug.

The emergence of drug-resistant strains of tuberculosis (TB) has led to increased use of second-line ATT. Although less common LDE is one of the cutaneous drug reactions which in very rare instances progresses into erythroderma. We need to be vigilant about such uncommon presentations so that a timely diagnosis and management can be done.

Declaration of patient consent

A written informed consent was obtained from the patient for the publication of her clinical images and other clinical information.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.