Unilateral lymphoedema of lower limb: an unusual presenting feature of hidden tuberculosis verrucosa cutis of foot

Abstract

A 42-year-old Indian farmer presented with gradually progressive swelling of the right lower limb for the last 20 years. There were few verrucous plaques over the right foot for the same duration. Those plaques were initially ignored and mistaken as lymphoedema-induced secondary changes by primary care physicians. Histopathology of the skin lesion showed pseudoepitheliomatous hyperplasia with upper dermal granulomatous infiltrate and a diagnosis of tuberculosis verrucosa cutis was suspected. Subsequently, the lesions as well as lymphoedema improved significantly with antitubercular therapy.

Background

Tuberculosis verrucosa cutis (TVC) presents classically as thick warty plaques over the extremities and sometimes over the buttocks. Involvement of the lymphatic system causing lymphadenopathy and lymphoedema are known complications of tuberculosis infection. However, such presentation in the setting of cutaneous tuberculosis is rare. We describe an unusual presentation of TVC presenting with unilateral lymphoedema of the limb for many years in an otherwise healthy 42-year-old man. It was mistaken for primary lymphoedema, leading to unnecessary investigations and delay in diagnosis and treatment.

Case presentation

A 42-year-old Indian man, farmer by occupation, presented with gradually progressive swelling of the right lower limb for the last 20 years. He noticed minimal diurnal variation of the swelling and it was associated with a mild dragging sensation. He did not give any history of lump in the inguinal region, swelling of the scrotum or pain in the affected limb. There was no history of fever or any other systemic complaint. He was following up with primary care physicians and general surgeons with a diagnosis of lymphoedema. The patient noticed verrucous plaques over the sole and lateral part of his foot for almost the same duration. The plaques initially appeared over the sole and had a very slow progression over the years. Cutaneous lesions were largely asymptomatic and there was no discharge from the lesions. He was otherwise well-built with adequate nutritional status. There was moderate diffuse non-pitting oedema involving the foot, leg and up to the mid thigh region (figure 1). The apparent increase in limb length due to swelling of the feet (figure 2) was causing difficulty in wearing footwear. There was increase in limb girth of 2.5 cm and 1.5 cm at the mid leg and mid thigh level, respectively, in the affected limb. No increase in temperature, erythema and tenderness was detected in the examination. Large verrucous plaques were present over the sole of the right foot (figure 3) and smaller, firm, less verrucous lesions over the dorsal aspect of the forefoot, ankle and the leg. Two small plaques were noticed over the right knee (figure 4). The plaques were ill-defined and freely movable over the underlying structures. There was no local or regional lymphadenopathy.

Figure 1.

Diffuse oedema of the right lower limb with verrucous plaques over the right foot and leg.

Figure 2.

Swelling of the foot with verrucous plaques over the margin of the foot and dorsum.

Figure 3.

Verrucous plaque over the sole.

Figure 4.

Two small scaly plaques over the knee.

Investigations

Routine blood investigations and chest X-ray were within normal limits. X-ray of the limb showed only increase in soft tissue thickening, with no bone changes. Ultrasound of the whole abdomen and pelvis did not reveal any abnormality and venous Doppler of limb revealed normal superficial and deep venous flow, with no evidence of deep venous thrombosis. Skin biopsy from a lesion over the ankle showed pseudoepitheliomatous hyperplasia of the epidermis with marked hyperkeratosis and acanthosis (figure 5). There was moderately dense infiltrate predominantly in the upper dermis composed of plasma cells and lymphocytes, along with epitheloid cell granulomas and multinucleate giant cells (figures 6 and 7). There was no evidence of any fungal profile in histopathology, and Ziehl-Neelsen stain and periodic acid–Schiff stain were negative. Tubercular as well as fungal culture from the tissue specimen and cartridge-based nucleic acid amplification test for Mycobacterium tuberculosis were negative. Mantoux test was negative with reading 0×0 cm.

Figure 5.

H&E (10×) staining of skin biopsy showing follicular plugging, pseudoepitheliomatous hyperplasia and inflammation in upper dermis.

Figure 6.

H&E (20×) staining of upper dermis having non-caseating epithelioid cell granulomas along with Langhans giant cells.

Figure 7.

Skin biopsy (H&E 40×) showing non-caseating granulomatous infiltrate and plasma cells.

Differential diagnosis

Initially, he was diagnosed to have lymphoedema probably secondary to lymphatic filariasis and associated secondary skin changes. A second diagnosis of podoconiosis was also considered as the patient belongs to an endemic region with prevalence of volcanic soil and the presentation with firm non-pitting oedema over the lower part of the leg. However, the verrucous plaques over the sole of the foot were unusual and difficult to explain due to lymphoedema-related changes. Discrete lesions over the ankle and scaly plaques over the knee were suggestive of sporotrichoid spread of the lesions which brought the clinical diagnosis of TVC and chromoblastomycosis. Histopathological features were also suggestive of granulomatous inflammation, supporting tubercular or deep fungal infection. Due to the absence of eosinophils in the dermal infiltrate and the inability to identify organism in histopathology and culture, and the area being endemic for tuberculosis, we considered starting therapeutic trial with antitubercular therapy with the provisional diagnosis of TVC with secondary lymphoedema. Technical and various host-related factors could be the reason for the false negative mantoux test result.

Treatment

The patient was started on antitubercular therapy with isoniazid, rifampicin, pyrazinamide and ethambutol according to category 1 regimen of National Tuberculosis Elimination Programme. He was also advised for compression stocking, foot elevation and avoidance of prolonged standing.

Outcome and follow-up

There was significant reduction in size of the verrucous plaques after 2 months of antitubercular therapy, with complete resolution of the plaques over the margin of the foot and partial flattening over the sole and dorsum with mild decrease in limb oedema (figure 8). On completion of the antitubercular therapy, all verrucous plaques over the dorsum and sole of the foot subsided completely, with significant reduction of the lymphoedema (figure 9A–C).

Figure 8.

Post-treatment picture of the foot with improvement in oedema and subsidence of plaques over the margin of the foot after 2 months of treatment.

Figure 9.

Complete resolution of the plaques over the sole (A), lateral aspect of the foot (B) and dorsum (C), with significant reduction of lymphoedema.

Discussion

Acquired unilateral lymphoedema of the lower limb can be of various causes.¹ In endemic areas, lymphatic filariasis remains the most common cause and many of the patients receive treatment for filariasis, irrespective of the specific diagnosis.² Podoconiosis, also known as endemic filariasis, occurs due to lymphatic obstruction by tiny particles of soil penetrating through the skin. It manifests as oedema predominantly over the lower part of the leg and foot.³ Lymphoedema can also be a manifestation of tuberculosis due to lymphangitis or lymphadenopathy, causing accumulation of lymph in the draining area. However, cutaneous tuberculosis with lymphoedema as the primary presenting feature has been described rarely in the literature. Cutaneous tuberculosis in the form of lupus vulgaris,⁴ verrucous tuberculosis⁵ and deep fungal infection such as chromoblastomycosis⁶ can present with lymphoedema of the affected limb. It is of utmost importance to do a complete cutaneous examination of the draining area and the regional lymph node group. There can be skin changes secondary to long-standing lymphoedema in the form of secondary lymphangiectasias manifesting clinically as solid papules, plaques and pseudovesicles, which sometimes can be oozy.⁷ It can be verrucous at times, leading to elephantiasis nostras verrucosa.⁸ Those skin changes are usually limited to the lower part of the leg and the dorsum of the foot. But, involvement of the sole and margin of the foot, and skip lesions over the ankles and knees, as seen in our case, are unusual and difficult to explain with lymphoedema-induced changes. Cutaneous tuberculosis can have varying manifestations and atypical presentations in endemic areas and can pose a diagnostic challenge. TVC especially can be multifocal,⁹ associated with oedema of the limb⁵ and even present as acquired keratoderma of the foot.¹⁰ The diagnosis of cutaneous tuberculosis was supported by the finding of upper dermal granulomatous infiltrate in our case. As TVC is paucibacillary type of tuberculosis, the culture can be negative as well as molecular tests.¹¹ Mantoux test with purified protein derivative sometimes can provide additional help in making the diagnosis but was negative in our case. It has limited diagnostic value in endemic countries like India.¹² In suspected cases, therapeutic trial with antitubercular therapy is considered diagnostic.¹³ The lymphoedema usually does not improve completely with treatment in long-standing cases due to sclerosis and blockage of the lymphatics following subsidence of initial inflammation. After starting antitubercular treatment, our patient had significant improvement in verrucous plaques at 2 months and complete resolution after treatment completion at 6 months, along with significant improvement in oedema of the leg. This case has been reported to highlight an atypical presentation of cutaneous tuberculosis.

Patient’s perspective.

I am extremely grateful to the doctors for saving my limb. I almost lost hope after such long years of suffering. But after the diagnosis was made, I was happy and within 1 month of starting treatment, I started to see improvement. I am still getting improvement and I am hopeful that everything will be cured.

Learning points.

• Tuberculosis verrucosa cutis (TVC) can have a long indolent course.

• Lymphoedema can be an unusual manifestation and presenting feature of TVC.

• If cutaneous changes are ignored, it can lead to unnecessary investigations and delay in diagnosis and treatment.