Eosinophilic Pustular Folliculitis Post Chemotherapy in a Patient of Non-Hogkins Lymphoma: A Case Report

Abstract

Eosinophilic pustular folliculitis (EPF) was originally described by Ofuji in Japanese patients without any systemic disease. Later it was widely associated with HIV. Lately a large number of hematological malignancies have been associated with EPF. We hereby report an association of non-Hogkins lymphoma with EPF, probably the first in Indian context.

What was known?

Eosinophilic pusular folliculitis is known to be associated with HIV and hematological malignancies, following chemotherapy.

Introduction

Eosinophilic pustular folliculitis (EPF) originally described in healthy individuals has been known to be associated with HIV. Its association with HIV and hematological malignancies with underlying immunosuppression indicates an immunological basis for pathogenesis. There have been six reports of association of EPF with non-Hogkins lymphoma till date. We hereby report the first case of such an association in India.

Case Report

A 64-year-old female who was a previously diagnosed case of non-Hogkins lymphoma of the splenic marginal zone type presented with a 7 month history of intense pruritus associated with itchy papular and pustular lesions over the face, scalp, back and proximal extremities.

The patient had received chemotherapy consisting of Bendamustine and rituximab which were given for six cycles following which she was in complete remission. The patient had presented to us 5 months after stopping chemotherapy. She gave history of multiple episodes of intense pruritus and history of noticing crops of papules and pustules which started from third cycle of chemotherapy and persisted till the time she presented to us. The patient had received treatment in the form of systemic and topical antibiotics, antihistaminics, topical steroids and antiscabetic medications with no relief of symptoms.

Cutaneous examination revealed multiple excoriated follicular oriented papules and pustules over back, scalp and proximal extremities [Figure 1]. The palms, soles and oral cavity were relatively spared. The patient was investigated with a differential diagnosis of eosinophilic folliculitis, infective folliculitis such as bacterial folliculitis and pityrosporum folliculitis, infestations such as scabies and demodex folliculitis, papular urticaria. Other conditions like atopic dermatitis and prurigo were also considered.

Figure 1.

Clinical photograph showing close up of follicular oriented papules and pustules on the forearm

KOH and Gram stain from pustules did not reveal any organisms and bacterial cultures were sterile. The ELISA for HIV was negative and markers for hepatitis B and C were negative. A serial comparison of complete hemogram revealed consistent eosinophilia which had started from the second cycle of chemotherapy and was persisting. The absolute eosinophil count was 2968 per cubic millimeter at the time of presentation. The other hematological parameters were within normal limits. A skin biopsy revealed predominantly deep perifollicular infiltrate of polymorphs (predominantly eosinophils and few neutrophils) and few lymphocytes [Figure 2] and follicular spongiosis. Moderately dense infiltrate of eosinophils and neutrophils was also seen in upper and mid dermis [Figure 3].

Figure 2.

(H and E ×40) Infiltrate composed of eosinophils lymphocytes and neutrophils around the base of hair follicle with spongiosis of follicular epithelium

Figure 3.

(H and E ×40) Dense infiltrate in upper and mid dermis composed predominantly of eosinophils

Based on these findings a diagnosis of eosinophilic folliculitis was made and the patient was started on tablet dapsone 1 mg/kg along with topical steroids in the morning and topical tacrolimus at night. Following the treatment there was a marked symptomatic improvement of itching. There was a fall in absolute eosinophilic count which ran parallel with improvement in the clinical condition.

Discussion

EPF was first described by Ofuji in 1970 in three Japanese patients without any systemic involvement. The name HIV-associated eosinophilic folliculitis was coined by Rosenthal et al., to distinguish the eruption in the latter group of patients which was felt should be considered a distinct entity.[1] There are three variants: Classic EPF, immunosuppression-associated (mostly HIV-related), and infancy-associated EPF.[2] Eosinophilic folliculitis is now being associated in patients with hematological malignancies and those taking chemotherapy or undergoing other modalities of treatment for the same.

It is clinically characterized by recurrent crops of sterile pruritic follicular papulopustules in well defined areas such as the face (85%), back (59%) and extensor surface of upper extremities. The lesions tend to spread centrifugally. They subside leaving a slight pigmentation. The skin lesions wax and wane often taking a chronic course. Peripheral blood eosinophilia is seen in 50% of the patients.[3] Histological features include spongiosis of the follicular epithelium, and infiltration of the outer root sheath of the hair follicle and the perifollicular dermis by eosinophils, neutrophils and mononuclear cells.[3]

Eosinophilic folliculitis has been reported in patients with hematological malignancies including multiple myeloma,[3] Waldestrom's macroglobulinemia,[3] non-Hogkins lymphoma,[3,4,5,6,7,8] Hogkins lymphoma,[9] acute myeloid leukemia,[3,10] chronic lymphatic leukemia,[11] aplastic anemia,[12] polycythemia vera.[13] Like in our patient, the patients described presented with folliculitis months after hematological malignancy onset. All the patients were on some modality of treatment including bone marrow transplant, stem cell transplant or polychemotherapy. The only exception was the patient by Roger et al., who developed the pruritic eruption before any chemotherapeutic treatment.[6] The chemotherapeutic agents used in the patients were different so none could be directly implicated in the development of this disease.[9] The clinical features however do not differ from the classical disease. In all other studies including our patient the morphological characteristics did not vary greatly from the classical disease. There was no infective etiology and all had a peripheral eosinophilia at the time of relapse.

The pathogenesis of this condition is unknown. It is known to be a consequence of disturbance of immune function.[14] It is not clear if eosinophils play a primary role in this disorder or, whether they are an allergic response to an unknown stimulus. Eosinophils act as end-stage effector cells. The proposed mechanism of action in chronic lymphocytic leukemia is clonal expansion of Th2 cells which produce interleukin 5, thereby stimulating eosinophils.[9,10] In a study involving five patients, lesional skin was examined using monoclonal antibodies, anti-leukocyte adhesion molecule, anti-endothelial cell adhesion molecule 2, and anti-vascular cell adhesion molecule 1 by immunohistochemical tests. Increased expression of ICAM 1 was noted on the keratinocytes of the hair follicle but not in the epidermis. Increased expression of VCAM1 and endothelial cell adhesion molecules was also noted around the hair follicle. These factors cause selective migration of eosinophils and lymphocytes to the hair follicles.[15] In view of pruritus, edema, tissue eosinophilia and presence of degranulated mast cells around hair follicles, it has been proposed that mast cells may play an important part in the pathogenesis of EPF.[3] Although considered to be a sterile folliculitis, infective etiology has also been proposed as one of the mechanisms of occurrence in only one study.[16] It has been suggested that the patient developed intense allergic reaction to an infective agent notably the fungus pityrosporum which proliferated markedly following immunosuppression with polychemotherapy.[9]

Greater awareness of the disease entity in hematological malignancies is required in order to differentiate it from drug reaction to chemotherapeutic agents and cutaneous metastasis of hematological malignancies. We report this case due to its rarity in Indian literature.

What is new?

This is the first report of EPF occurring in a patient with non-Hogkins lymphoma in an Indian patient.