Podoconiosis: Clinical spectrum and microscopic presentations

Abstract

Background: Podoconiosis is a skin Neglected Tropical Disease (skin NTD) that causes lymphoedema, and affects barefooted subsistence farmers in some tropical countries. The clinical presentation and histopathologic correlates of podoconiosis have been understudied. Here, we systematically document the clinical and histopathologic spectrum of podoconiosis.

Methods: This is a cross-sectional study in Durbete, Ethiopia from February 2018 to October 2019. Dermatologists performed a patient history, physical examination, filariasis test strip, and skin biopsy for histopathologic examination. The results were summarised and a descriptive statistical analysis and Wilcoxon rank sum test with continuity correction was done.

Results: We recruited 289 patients for the study, 178 (61.6%) had stage 1 or 2 podoconiosis, and 111(38.4%) stage 3 to 5 podoconiosis. 188 (64.1%) had a family history of podoconiosis. In 251 (86.9%) patients, both legs were affected by podoconiosis and in 38 (13.1%) only one leg was affected. 220 (77.5%) patients had warty lesions, 114 (39.4%) had nodules. The median number of episodes of Acute Dermato-Lymphangio-Adenitis (ADLA) reported by the patients in the last three months was 2 (interquartile range (IQR) 1-4). Increased episodes of ADLA were significantly associated with stage 3-5 podoconiosis (P = 0.002), while burning pain in the feet was more common in stage 1 or 2 podoconiosis. Stage 3-5 disease was histopathologically characterised by epidermal and dermal thickening, verrucous acanthosis, inflammatory cell infiltrates (predominantly lymphoplasmacytic), dilated and ectatic and a reduced number of lymphatic vessels, eccrine ductal hyperplasia, and sclerosis such as thickened collagen bundles.

Conclusion: We provide a detailed description of the different clinical patterns, associated clinical findings and the histopathologic spectrum of podoconiosis at different stages of the disease. Our observations should serve as a guide to classifying patients with podoconiosis for prognostic assessment and treatment decision.

Fig 1. Most common characteristics of the various stages of podoconiosisin, in Durbete Podoconiosis Prevention and Treatment Centre, Durbete, Ethiopia, February 2018 to October 2019.

A) Stage 1: overnight reversible oedema, with increased skin marking and hyperkeratosis on the base of the toes of both the right and left foot. B) Stage 1: splaying of the right forefoot, accentuation of the skin markings on the metatarsophalangeal joint. C) Stage 2: bilateral lymphoedema below the knee. Area of scarring is seen on the lower leg and foot (from traditional bloodletting). Hyperpigmented, warty hyperkeratotic papules covering the dorsum of the feet extending to the ankle. Nodules on the right forefoot. D) Stage 2: Pitting lymphoedema below the knee, with dry skin. E) Stage 2(right foot) and stage 3 (left foot). Right foot: pitting lymphoedema on the shin, few papules and nodules on the dorsum anterior one third of the foot and toes. Left foot: smooth surface with multiple nodules and tumorous masses covering the whole foot and flexural ankle with extension to the anterior distal one third of the lower leg. The foot is totally deformed and the toes are no longer visible. Based on the extension of the nodules the right foot is stage 2 (nodules below the ankle only) and the left foot stage 3 (nodules extending above the ankle). F) Stage 3: Bilateral lymphoedema. On the right leg the swelling is pitting on the proximal half of the lower leg and non-pitting fibrotic edema on the distal one third of the lower leg and foot. Scattered, infiltrative papules on the dorsal distal one third of the foot and toes. Hyperkeratotic and depigmented rough papules and nodules covering the distal one third of the left lower leg, and dorsum of the foot. G) Stage 4 (right) and stage 2 (left). Right foot: non pitting oedematous swelling of the leg extending above the knee with an area of skin depigmentation around the ankle. Left foot: non pitting swelling of the leg below the knee. H) Stage 5: fibrotic globular swelling of the left foot and ankle with ankylosis of the ankle joint, multiple areas of scarring (from traditional bloodletting). I) Stage 5: right leg with nodules and rubbery to woody hard tumors on the dorsum of the foot with band like redundant skin on flexural ankle (pillowy oedema) and ankle fixation.

Fig 2. Clinical variations and complications of podoconiosis, in Durbete Podoconiosis Prevention and Treatment Centre, Durbete, Ethiopia, February 2018 to October 2019.

A) Stage 2 podoconiosis patient with Acute Dermato-Lymph-Angitis (ADLA) presenting with pitting oedema of the left leg with epidermal exfoliation on the distal half of the lower leg. B) Stage 3 fibrotic oedema of the left leg below the knee with sclerotic hyperpigmentation and hypopigmentation accentuated on the shin and a fibrotic ridge on the flexural ankle. C) Stage 2: Water-bag type oedema with pitting and soft swelling and a flask-like appearance with the neck around the knee and wider base on the ankle and oedematous foot with a smooth and dumpy surface around the shoe strap areas. D) Stage 3 podoconiosis, multiple nodules with plantar foot involvement. E) Asymmetric podoconiosis with right leg stage 3 diseases with fibrotic depigmented nodules on foot and above the ankle, while the left leg is not affected. F) Asymmetric lymphoedema with the right leg in stage1, and the left leg in stage 3 podoconiosis with depigmented nodules and toe fusion. G) Stage 5: oedematous right foot with scarring of the distal half of the dorsum of the foot, bone resorption of all the toes. H) Stage 3 podoconiosis with multiple coalescent nodules on the dorsum of the foot extending to the sole of the foot and above the ankle with maceration and oozing. I) Fibrotic lymphoedema of the right leg with a continuous sock-like yellowish crust covering the whole foot and lower leg, and band like skin invagination on the flexural ankle joint. J) Hyperpigmented warty papules coalescing and covering the lateral feet and cracking in moccasin-like configuration.

Fig 3. Histopathologic characteristics of podoconiosis in skin biopsies from 65 patients with stages 1 & 2 versus stages 3–5 podoconiosis, in Durbete Podoconiosis Prevention and Treatment Centre, Durbete, Ethiopia, February 2018 to October 2019.

A) Stages 1 podoconiosis: Basket woven hyperkeratosis, acanthosis, and ectatic and dilated lymphatic vessels (40X magnification). B) Stages 2 podoconiosis: Compact hyperkeratosis and acanthosis with elongated rete ridges, sclerosis with numerous linear, perpendicular arranged capillaries in the papillary dermis (20X magnification). C) Stages 3 podoconiosis: Verrucous hyperplasia of the epidermis (40X magnification). D) Stage 3 and 4 podoconiosis: Dense dermal infiltrate with lymphocyte, histocyte and plasma cells (100X magnification). E) Stage 3 podoconiosis: Compact hyperkeratosis and acanthotic epidermis with increased dermal vasculature (20X magnification). F) Stage 4 podoconiosis: Sclerosis vessel with perivascular infiltrate (100X magnification). G) Stage 4 podoconiosis: Dilated eccrine gland with area of sclerosis around the gland (100X magnification). H) Stage 5 podoconiosis: Sclerosis dermis (both papillary and reticular) with loss of adenexal structure and vasculatures (20X magnification).