Polymyxin-B-induced rapidly progressive lichen planus pigmentosus confined to face in a patient of multidrug-resistant pneumonia

Dear Editor,

The most frequent adverse drug reactions of intravenous polymyxin (PMB) are neurotoxicity and nephrotoxicity.^[1] “Polymyxin-B-induced skin hyperpigmentation (SH)” has been described previously.^[2,3] However, we report here the first case of PMB-induced lichen planus pigmentosus (LPP) limited to the face and neck.

A 40-year-old lady, known case of type-2 diabetes mellitus and hypertension, was admitted with fever along with respiratory distress due to Klebsiella pneumoniae, that was sensitive to PMB and colistin. Therefore, she was treated with intravenous PMB (500,000 units, intravenously, q.12) along with daily telmisartan 40 mg and anti-diabetic medications (metformin 1 g and glimepiride 2 mg), which she had been taking for years. After 4 days of starting PMB, the patient noted a rapid onset of mildly itchy blackish discoloration of the face, extending to the neck. There was no history of prior cosmetic use.

On examination, she had diffuse slate-grayish to blackish hyperpigmented macules restricted to the face and neck, more concentrated over the temple area, sides of face, and perioral region [Figure 1a-c]. Her other body areas, nails, oral, and genital mucosae were entirely spared.

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Figure 1:

(a) Picture showing slate-grayish patches over the left side of face; (b) Picture showing ill-defined slate-grayish to blackish hyperpigmented macule over perioral region; (c) Showing slate-grayish patches over the right side of face.

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We kept differentials of drug-induced SH, Vitamin B12 insufficiency, Addison’s disease, hemochromatosis, and pigmented contact dermatitis due to cosmetics. Dermoscopy (DermLite DL4 dermatoscope, ×10 magnification, polarized) showed reticular pattern of dots and globules, non-specific granules/irregular dots, and irregular peppering [Figure 2a and b]. A patch test done with Indian standard series and cosmetic series turned out to be negative. A 4-mm skin biopsy revealed basal cell melanization along with significant pigment incontinence in the upper dermis, along with subtle vacuolar changes [Figure 2c].

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Figure 2:

(a) Dermoscopy (DermLite DL4 dermoscope, ×10 magnification, polarized) reticular pattern of dots and globules, non-specific granules/irregular dots and irregular peppering, (b) Closer view showing reticular pattern (DermLite DL4 dermoscope, ×10 magnification, polarized) (c) Histopathology reveals basal cell melanization along with significant pigment incontinence in the upper dermis along with subtle vacuolar change (hematoxylin and eosin, ×100).

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Laboratory investigations (complete blood count, liver function test, kidney function test, serum ferritin, transferrin, vitamin B12, and early morning serum cortisol level) were within normal limits. The “Naranjo Adverse Medication Reaction Probability Scale” revealed (+2 for adverse event following medication administration, +1 for objective evidence confirmed, +2 for lack of any alternative reason, +1 prior conclusive reports = 6 points).^[4] In view of skin biopsy and dermoscopy findings, a final diagnosis of LPP was given. PMB was stopped on the 5^th day, and the patient was shifted to tigecycline 50 mg intravenously once daily for 7 days. There was no further development of new lesions or progression of skin lesions. We advised her to apply mometasone furoate 0.1% cream once daily for 2 weeks and thereafter, topical tacrolimus 0.1% ointment once daily at night. However, there was no improvement in hyperpigmentation even after 3 months of follow-up.

In a recent cohort study, “PMB-induced skin hyperpigmentation” was noted by the 3^rd day of treatment for 60 patients who were treated with PMB for 14 days. The condition recovered gradually after discontinuation of PMB.^[1-3,5,6] Although the pathogenesis of “PMB-induced LPP” is unknown, it may be caused due to either histamine release or activation of an inflammatory process or due to oxidative stress, which needs to be explored further.^[6] Other medications such as methadone,^[7] gold therapy,^[7] and tamoxifen^[8] have also been reported to cause LPP. Kura and Sonawane et al. reported a case of PMB induces SH, dermoscopy revealed diffuse muddy brown hyperpigmentation with perifollicular prominence and annular brown or gray circles. Additionally, a biopsy showed hypermelanosis of the basal layer and minute particle deposition in the dermis.^[2] However, these findings did not align with ours, ruling out drug-induced hyperpigmentation^[3] and pigmented contact dermatitis.^[9,10] Table 1 depicts the dermoscopic findings of the differential diagnoses considered.

In conclusion, PMB-induced LPP represents a new entity that dermatologists should be aware of for the early detection of adverse events.