12. A Young Man with Mottled Pigmentation on Trunk

Piyush Kumar¹

(1)

Katihar Medical College and Hospital, Katihar, India

Piyush Kumar

Keywords

ArsenicArsenicosisMottled pigmentationKeratotic papulesSquamous cell carcinomaBasal cell carcinomaBowen disease

A 27-year-old male, from rural area of West Bengal, presented with progressive, asymptomatic, pigmentation of the trunk of 5 years duration, and rough palm and soles of 2 years duration. He developed both hyperpigmented and hypopigmented flat lesions on upper back 5 years back which had progressed to involve the trunk completely. He started developing small, rough, solid elevated lesions on the palms and soles 2 years back. These lesions had been increasing in number since then and were coalescing to form bigger lesions. The lesions were asymptomatic, but interfere with walking and manual activities with hand. Also, he complained of slight breathlessness on exertion. Two of his family members and many persons from his neighborhood were suffering from similar skin lesions, though of different degree of involvement. On enquiring, people in his locality were drinking groundwater without processing. On dermatological examination, there was diffuse hyperpigmentation of the trunk, along with multiple hyperpigmented as well as hypopigmented macules. Additionally, a few hyperpigmented, hyperkeratotic papules and plaques were noted (Fig. 12.1). Palm and soles were notable for the presence of discrete as well as confluent hyperkeratotic papules (Fig. 12.2). Rest of the mucocutaneous examination was non-contributory. Patient was referred to pulmonologist and internist for the evaluation of breathlessness. Based on clinical presentation, what is your diagnosis?

1.

Pigmented xerodermoid
2.

Pityriasis versicolor
3.

Dowling Degos disease
4.

Chronic arsenicosis

../images/471276_1_En_12_Chapter/471276_1_En_12_Fig1_HTML.jpg — Figure 12.1

Multiple hyperpigmented as well as hypopigmented macules on the back. There are a few lesions of arsenical keratoses too. (Courtesy: Dr. Anirban Das)

../images/471276_1_En_12_Chapter/471276_1_En_12_Fig2_HTML.jpg — Figure 12.2

Multiple discrete and confluent keratotic papules present bilaterally on palms (Courtesy: Dr. Anirban Das)

Diagnosis

Chronic arsenicosis

The clinical presentation (both hyperpigmented and hypopigmented macules and patches of covered parts along with hyperkeratotic lesions on palms and soles) was characteristic of chronic arsenicosis. Further confirmation was done by demonstrating higher level of arsenic in urine (84 μg/L), and drinking water (132 ppb).

Discussion

Arsenicosis is a chronic multisystem disorder resulting from high level of arsenic in the body. Though cases have been reported from many parts of the world, the two worst affected areas in the world are Bangladesh and West Bengal, India. Arsenic exposure may occur from inhalation, and absorption through the skin, but is mostly by ingestion of contaminated drinking water. Other sources of arsenic include agricultural pesticides and herbicides; fungicides and insecticides; wood preservatives; paints; cosmetics; and manufacture of semiconductors, light emitting diodes, lasers and microwave circuits [1]. Chronic arsenicosis may be seen in sheep dip workers, in vineyard workers using arsenical pesticides, and from drinking contaminated wine. Additionally, arsenic is present as a contaminant in many traditional remedies and long term ingestion of such medicines may cause the disease [2].

After ingestion, arsenic is mainly absorbed in small intestine and is metabolized in liver and excreted in urine. Arsenic is consumed mainly in two forms, arsenite (As +3) and arsenate (As +5). Arsenite (As 3+) binds with sulfhydryl groups in keratin filament and has a tendency to accumulate in the skin, hair, nails, and mucosae of the oral cavity, esophagus, stomach, and the small intestine. On the other hand, arsenate (As +5) is predominantly deposited in the skeleton. Arsenic, mostly the arsenite (As +3) form, binds with the sulfhydryl groups present in various essential compounds, e.g., glutathione (GSH), cysteine, and exerts its toxicity by inactivating up to 200 enzymes, especially those involved in cellular energy pathways, and DNA synthesis and repair. Arsenate (As +5) in addition to getting converted into arsenite (As +3) form, causes toxicity by ‘arsenolysis‘in which it replaces phosphate during glycolysis, resulting in ineffective generation of adenosine triphosphate (ATP). Other mechanisms include generation of reactive oxygen intermediates and metabolic activation processes causing lipid peroxidation and DNA damage. Arsenic induced carcinogenesis is believed to result from hypermethylation of DNA, particularly of the promoter region, resulting in inactivation of the tumor suppressor genes [3].

No system is spared in chronic arsenicosis, but skin is the most predominantly affected organ. The cutaneous manifestations are of diagnostic value and include pigmentary changes; keratotic papules and plaques; and various cutaneous malignancies. The pigmentary changes are reported to be the earliest and the commonest of all dermatological manifestations. The pigmentation can be diffuse (with trunk being affected most severely) or localized affecting skin folds. Another common pattern of pigmentation is fine hyperpigmented macules, known as ‘rain-drop pigmentation’. Simultaneously, depigmented macules appear on normal skin or hyperpigmented background resulting in a distinctive appearance of ‘leucomelanosis‘. Pigmentary changes is noted in mucosa too and blotchy pigmentation affecting the undersurface of the tongue or buccal mucosa is common. Another important examination finding is Mee’s lines (transverse bands of true leukonychia) in the fingernails and toenails [3].

Arsenical hyperkeratosis characteristically affects the palms and soles, and the involvement is graded as mild, moderate, or severe depending on the extent and severity. In the early stages of keratosis (i.e., the mild variety), the involved skin has an indurated, gritty feel with papules less than 2 mm in size. In the moderate variety, the lesions advance to form punctate, wartlike keratoses >2–5 mm in size. When the keratosis becomes severe, it may form keratotic elevations more than 5 mm in size and become confluent and diffuse. Keratotic papules may noted on dorsa of the extremities and trunk too [4].

The development of various cutaneous malignancies in chronic arsenicosis is quite common and may occur in the hyperkeratotic areas, as well normal appearing skin of the trunk, extremities, or head. The affected patients have a tendency to develop multiple lesions simultaneously or over a long period of time and lesions usually appear on the covered parts. Arsenic exposure has been associated with three types of skin cancers mainly—Bowen’s disease, basal cell carcinoma and squamous cell carcinoma [3].