A 5-year-old girl, diagnosed with multi-system langerhans cell histiocytosis (bone, liver, bone marrow and pituitary involvement), was started on induction chemotherapy (weekly cycles of vinblastine/prednisolone for 12 weeks). Two months later, she developed progressive bluish-black discolouration over the nose and fingertips along with darkening of the nail beds without any itching, pain, redness, numbness, trauma or sun exposure.

Several differentials were considered, Chikungunya fever is well reported for causing an acute, brownish-black, centrofacial hyperpigmentation [1]. It can persist for three to six months after resolution of infection [1]. However, our child had no fever, arthralgia or cytopenias to suggest an infectious aetiology. Addisonian hyperpigmentation, which commonly involves mucous membranes, flexures, palmar and plantar creases, the areola, genitalia and pressure points (elbows and knees), was ruled out clinically, as well as by the absence of hyponatremia, hyperkalemia and acidosis [1]. Hyperpigmentation in thyroid disorders also has a similar distribution as in Addison disease [2]; however, the thyroid function test was normal. Exogenous ochronosis, secondary to topical hydroquinone use, responsible for bluish-black hyperpigmentation of the sun-exposed areas of the face, was also ruled out as there was no history of such application; neither was henna applied locally [1,2].  She had no preceding redness, scaling, pain, injury or cutaneous eruptions to suggest post-inflammatory hyperpigmentation [3]. Acanthosis nigricans, although classically noted over the nape of the neck, axilla and groin, can also develop over the face [4]. However, our child had neither hyperglycemia nor obesity and the lesion in question lacked the characteristic velvety thickening of acanthosis nigricans [3]. The involvement of distal phalanges, interphalangeal joints and oral mucosa, characteristic of Vitamin B12 deficiency, was absent in our child [2]. Moreover, her red blood cell indices were normocytic and normochromic, ruling out this possibility. Drug-induced acral hyperpigmentation was considered after ruling out other differentials and vinblastine was discontinued, following which the hyperpigmentation faded over a period of 3 weeks, but did not disappear completely.

Fig.1

Vinca alkaloids are notorious for causing extra-vasation injury [4]. Supravenous hyperpigmentation has been reported with the ABVD regimen which includes vinblastine (however, the causative drug was not implicated) [5]. Vinorelbine, a vinca alkaloid, in high doses is known to cause acral erythema [6].  Although drug-induced hyperpigmentation is responsible for 10-20% cases of acquired hyperpigmentation [2], it has not been reported with either vinblastine or prednisolone. Possible mechanisms of drug induced acral hyperpigmentation include increased melanin synthesis (secondary to cytotoxic effect on melanocytes), cutaneous drug accumulation or iron deposits following dermal vascular damage, and increased blood flow to acral areas causes drug deposition [4,5].

Contributors: AC: collected and analyzed data, drafted the paper; PKS: conceptualized, analysed data, drafted and critically appraised the manuscript.

Funding: None; Competing interest: None stated.

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