Borrelial Lymphocytoma Cutis: A Diagnostic Dilemma

Abstract

Lymphocytoma cutis (LC) is one of the most common types of cutaneous B cell pseudolymphoma. Borrelial LC occurs most commonly in areas endemic for Ixodes ricinus tick in Europe, and it is rare in North America. The disease is rarely seen in India and may cause diagnostic difficulties for dermatologist residing in parts of the world that are not endemic for Lyme disease. The diagnosis is critical as LC may present as the only early manifestation of Lyme disease. Herein, we have presented a case of borrelial LC in an 11-year-old boy of German descent, residing in India.

Introduction

What was known?

1. Lymphocytoma cutis (LC) is one of the most common types of cutaneous B cell pseudolymphoma.

2. Borrelial LC occurs commonly in areas endemic for Ixodes ricinus tick in Europe and North America. This disease is rarely seen in India.

The clinical and histological distinction of borrelial lymphocytoma cutis (LC) from other papulonodular lesions, including persistent arthropod bite reactions, nodular scabies, sarcoidosis, borderline tuberculoid Hansen's disease, granuloma annulare, and primary cutaneous B cell lymphoma may be difficult in regions that are not considered endemic for Lyme disease. Borrelial LC occurs primarily in Europe and is the rarest of the dermatologic hallmarks of Lyme disease. The diagnosis is critical as it may be the only early manifestation of Lyme disease.[1]

Case Report

An 11-year-old German boy, resident of India, presented with firm, reddish lesions on the scrotum of 2 months duration. The lesions were mildly itchy and had started as a solitary, reddish, raised lesion and later progressed to involve the anterior part of the scrotum, the root of the penis, and the areas adjacent to it, in an annular pattern over a period of 2 months. He was applying a mild topical corticosteroid with partial relief to itching, but no regression of the lesions. There was no history of similar lesions or any itching in family members and no contributory symptoms such as fatigue, fever, headache, or pain. There was no history of preceding insect bites or skin lesions.

Clinical examination revealed intensely erythematous linear plaque, 3-cm in length on the anterior aspect of the scrotum, alongside the median raphe on the left. The plaque progressed along the root of the penis and the region adjacent to it in an annular pattern. A single erythematous nodule was also present on the right side of the median raphe [Figure 1a and b]. There was no regional lymphadenopathy and no other lesions elsewhere on the body. Systemic examination was non contributory. At this point, on the basis of the history and clinical examination, a differential diagnosis of a persistent nodular insect bite reaction, granuloma annulare, lymphocytic infiltrate, or cutaneous sarcoidosis was made. Routine hematological examination was normal. Chest X-ray, Mantoux test, and serum angiotensin converting enzyme (ACE) levels were normal.

Figure 1.

(a) Erythematous plaque on the scrotum and the root of the penis attaining an annular configuration. (b) Single erythematous nodule on the right side of the median raphe

On histopathological examination a diffuse, dense infiltrate of lymphocytes was seen throughout the dermis, admixed with histiocytes [Figure 2]. The lymphocytes revealed no atypia. Immunohistochemical analysis revealed diffuse staining for CD 20 and variable staining for CD 3 in the small lymphocytes. CD 30 cells were negative [Figure 3].

Figure 2.

Diffuse, dense infiltrate of lymphocytes throughout the dermis (H and E, ×10)

Figure 3.

Lymphoid cells both of B and T phenotype observed with CD3 and CD20 staining

On further probing, the parents revealed of having taken a camping trip to the Shenandoah Valley in the West Virginia region in southern United States, after which they travelled to Germany where the lesions appeared. After their return to India, 2 months later the lesions had progressed to the current size.

This urged us to consider the possibility of borrelial LC, and an enzyme-linked immunosorbent assay (ELISA0 test for Borrelia burgdorferi antibodies was done, which was positive for both IgG and IgM antibodies. This was followed-up by western blotting, wherein the patient tested positive for IgG antibodies (8 of the 10 bands were reactive) and negative for IgM antibodies (1 of the 3 bands were reactive). This was suggestive of an acute persisting infection. The patient was subsequently put on amoxicillin 500 mg, three times daily for 1 month. After 3 weeks, the lesions showed a partial remission, wherein the erythema and infiltration had decreased significantly [Figure 4a and b].

Figure 4.

(a and b) Partial remission of the lesions. Significant decrease in the erythema and infiltration of the plaques

Discussion

LC is one of the most common types of cutaneous B cell pseudolymphoma.[2] It can be induced by various antigenic stimuli, including arthropod bites, vaccination, and drugs among others.[3,4,5,6,7,8] Borrelial LC occurs most commonly in areas endemic for Ixodes ricinus tick [Figure 5a and b] in Europe and is rare in North America. It seems to be more common in children than in adults[6] and appears to be the rarest of the dermatological manifestations of Lyme disease. Borrelia species may selectively disrupt different organ systems, leading to variations in disease manifestations from region to region.[9] Erythema migrans (EM) and acrodermatitis chronica atrophicans (ACA) are the other two dermatological hallmarks of Lyme disease.

Figure 5.

(a) Ventral aspect of the tick Ixodes ricinus, (b) Dorsal aspect of the tick Ixodes ricinus

Borrelial LC typically presents as a bluish-red plaque or nodule that varies from one to a few centimetres in diameter. The most common sites of onset of LC associated with B. burgdorferi infections include the nipple, genital area, and earlobe.[2] The sites of predilection may reflect sites of initial transmission or areas of low body temperature, where disseminated Borrelia prefer to remain.[10] Lesions are typically noted 30-45 days after a tick bite and appear most frequently during the months of August and September.[11] All infected individuals may not recall or give a history of a tick bite, as in our patient. The lesions in our patient appeared 2 months after his visit to North America and Germany and the lesions appeared on the scrotum, in the month of August, consistent with the findings as mentioned in the dermatological literature.

History of preceding EM may not always be present, and LC may rarely develop at the site of inoculation as a component of early disease on occasion preceding EM. On the other hand, predominantly in Europe, EM can persist as a plaque or nodule that coincides with the development of LC.[12] Moreover, LC can mimic primary cutaneous lymphoma, rendering diagnosis, and management challenging.[12,13]

The treatment recommended for borrelial LC involves administration of doxycycline 100 mg (twice daily) or amoxicillin PO 500 mg (thrice daily) for a period of 3-4 weeks. Our patient was given amoxicillin 500 mg (thrice daily) and showed partial remission of the lesions at 3 weeks.

The incidence of Lyme disease in India is unknown. The Ixodes ticks are said to be present in the Himalayan region of India;[14] therefore, the possibility that Lyme disease may exist in our country cannot be ruled out. Reports of borrelial LC or Lyme disease from India have been scarce. Mehta et al.[15] reported the occurrence of LC following excision arthroplasty, but the cause of the pseudolymphoma was not clearly delineated. Praharaj et al.[16] studied the seroprevalence of B. burgdorferi in northeastern India and demonstrated that 65 (13%) out of 500 persons were positive for B. burgdorferi specific lgG. Females showed higher positivity rate as compared to males and a higher prevalence rate was observed in the age group of 15-30 years in both sexes. Arunachal Pradesh showed higher seroprevalence rate (17.8%) as compared to other northeastern states. A single case of idiopathic LC was reported by Hasan et al.,[17] whereas Handa et al.,[18] prospectively screened 27 patients presenting with mono/oligoarticular disease of unknown aetiology for Lyme arthritis, wherein only 1 patient tested borderline positive for antibodies to B. burgdorferi, although only North American strain 2591 was used as an antigen in this study. Other isolated reports, include neuroretinitis secondary to Lyme disease seen in a South Indian female, hailing from the Nagarhole forest region,[19] and demonstration of Borrelia in the blood smear of a 15-year-old boy with Lyme disease from Shimla.[20]

Although our patient was not an Indian by origin and probably contracted the disease from North America or Europe, the purpose of presentation of the case was to alert dermatologists in India to consider the diagnosis of borrelial LC in travellers from epidemic areas and in individuals hailing from the forests of north, northeast, and south India.

What is new?

1. Isolated case reports of Lyme disease and lymphocytoma cutis from India exist.

2. Dermatologists in India should be aware and consider the diagnosis of borrelial LC in travellers from epidemic areas and in individuals hailing from the forests of north, northeast, and south India.