A Case Report of Necrotizing Eosinophilic Folliculitis Occurring After Rhus Ingestion

Introduction

Rhus (Toxicodendron succedaneum) is used in Korea as a medicinal plant to boost immunity. The leaves, roots and bark of the plant are boiled to make extracts, and then ingested per se or added when cooking chicken at home or specialized restaurants. Also, in oriental medicinal preparations, dried Rhus tree is used as an ingredient. In western countries, it can be found in private gardens and distribution of its seeds by birds can lead to it becoming established in public or urban areas. It is one of the most common plant families to cause allergic contact dermatitis worldwide.^1,2 Rhus contact dermatitis (RCD) is usually manifested as eczema, pompholyx, symmetrical maculopapular rash, urticaria, erythema multiforme and rarely vasculitis or fixed drug eruption.³

Eosinophilic folliculitis (EF) was first described as an idiopathic eruption of sterile pustules, papules, and plaques, preferentially involving the face, trunk, and extremities of men in the third and fourth decades of life.⁴ It is broadly divided into five major groups: (i) classical EF, or Ofuji disease, (ii) HIV-associated EF, (iii) infantile EF, (iv) cancer-associated EF, and (v) medication-associated EF.⁵ Necrotizing eosinophilic folliculitis is known as a rare variant of eosinophilic EF. It is associated with atopy and characterized histopathologically by dermal neutrophilia, eosinophilic vasculitis, ulceration and marked follicular destruction.⁶ Here, we report a 48-year-old man who developed necrotizing eosinophilic folliculitis after consuming Rhus. His pathergy reaction was positive, which may indicate a delayed type hypersensitivity reaction to Rhus ingestion.

Case

A 48-year-old man presented with painful pyodermic plaques with edema localized to his face (Figure 1A). The lesions developed 2 days after Rhus consumption. The patient had previous history of Rhus chicken consumption. He worked as a construction site supervisor; however, he had no exposure to halogen. He had been healthy without any systemic diseases. On physical examination, there were numerous tender, indurated plaques on the patient’s face and neck area. Several erythematous papular and pustular lesions were seen at the periphery of the plaques. The eruption was not associated with fever or other general symptoms. Full blood count, liver and renal function tests, fasting sugar, C-reactive protein and urinalysis were all within normal range. Cytoplasmic-antineutrophil cytoplasmic antibodies (c-ANCA), perinuclear-antineutrophil cytoplasmic antibodies (p-ANCA), antinuclear antibody (ANA) tests were also unremarkable. Evaluation for infection including serology for venereal disease research laboratory (VDRL) and human immunodeficiency virus (HIV) were negative, and cultures of peripheral blood and skin pustules were negative. Tzanck smear and fungal testing from skin lesions did not show any abnormalities. Routine stool tests on common pathogen and parasite screen were negative.

Figure 1 (A) Multiple pyodermic plaques with hemorrhagic eschar on the face. (B) The lesions cleared up leaving mild scarring 10 days later.

Three skin biopsies were taken from the face. Light microscopy findings revealed prominent superficial and deep lymphocytic inflammatory reaction with numerous eosinophilic and neutrophilic infiltrate in the follicular infundibulum and follicular spongiosis (Figure 2A). The epidermis was covered with serum crust with underlying neutrophilic and eosinophilic dermolysis. Eosinophilic abscesses were noticed in follicular infundibular orifices. Exocytosis of lymphocytes and eosinophils were noticed in the hair follicles (Figure 2B). There was a moderately dense lymphocytic inflammation, which extended around the superficial and mid-dermal vessels. The samples showed indications of vasculitic change, such as mild luminal intramural fibrin deposition and migration of eosinophils and neutrophils through the vessel wall. Slight perivascular dermal necrosis was noticed (Figure 2C). Periodic acid-Schiff stains for fungi were negative, and there was no evidence of viral cytopathic changes such as herpes infection or extravascular necrotizing granulomas.

Figure 2 (A) Skin biopsy showing perivascular and perifollicular inflammatory cell infiltration with numerous eosinophilic and neutrophilic infiltrate in the follicular infundibulum and follicular spongiosis. (Hematoxylin and eosin; x40), (B) The follicles showed exocytosis of both lymphocytes and eosinophils. Epidermal necrosis with underlying neutrophilic and eosinophilic dermolysis was also noticed. (Hematoxylin and eosin; x100), (C) Vasculitic changes with migration of eosinophils and neutrophils through the vessel wall with mild luminal intramural fibrin deposition. (Hematoxylin and eosin; x 200).

Based on the clinical and histological findings, the patient was diagnosed with necrotizing eosinophilic folliculitis and was treated with intravenous injections of 5mg dexamethasone twice a day along with oral dapsone at a dose of 50mg. Hydrogel (Intrasite gel 25mg, Smith & Nephew ©) was used as dressing material. The lesions improved rapidly within 10 days of commencing treatment and drug dose was tapered over a 2-week period. The lesions cleared up leaving mild scarring and there was no recurrence over a 1-year follow-up period (Figure 1B).

Discussion

Sometimes pathergic phenomenon occurs in EF patients with an atopic background and the term “necrotizing eosinophilic folliculitis” was proposed to describe this condition.⁶ The clinical manifestations of EF may be the result of an abnormal T helper (Th) 2-type immune response to a follicular antigen. Necrotizing eosinophilic folliculitis has been reported in patients with a range of immune dysregulatory states, such as atopy. It is characterized by significant tissue destruction, which differentiates it from EF.^6,7 T-cell dysregulation is an important factor in the pathogenesis of necrotizing eosinophilic folliculitis.⁶ Immune triggers such as bacteria can lead to an exaggerated type IV immune reaction in a Th2 cytokine-rich environment as in atopy. This may result in the pathognomonic destructive folliculocentric process in NEF.⁶ In atopy, cytokines like interleukin (IL)-4 and IL-5 are elevated. These cytokines may stimulate eosinophil proliferation and induce the infiltrates seen in necrotizing eosinophilic folliculitis.⁸ In this case, the patient had consumed Rhus, which is well known for its type-IV delayed hypersensitivity reaction. After contact, macrophages present the antigen to Th-cells, then the sensitized Th-cells start to release cytokines and chemokines. The excessive inflammatory response may cause damage to the keratinocytes resulting in epithelial tissue disruptions.⁹ Thus, the necrotizing ulcerative features noticed in this patient may have been initiated by a delayed-type hypersensitivity reaction to Rhus and aggravated by miscellaneous causes as shown by his positive pathergic reaction.

As our patient shared features with a number of conditions, it was difficult to diagnose and find proper treatment. Our differential diagnosis included Sweet’s syndrome, pyoderma faciale, eczema herpeticum, superficial granulomatous pyoderma and halogenoderma. Sweet’s syndrome presents as reddish blue or violet plaques or nodules that uncommonly are confined to the face. Lesions may be studded with pustules. Skin biopsy reveals dense, diffuse neutrophilic infiltrate in the reticular dermis with leukocytoclasis, which was not a prominent feature in our case.¹⁰ Pyoderma faciale presents as tender follicular papules and pustules, nodules with explosive onset. Biopsy reveals perifollicular and perisebaceous gland abscesses with neutrophils rather than eosinophils.¹² Eczema herpeticum may begin as sudden outbreaks of painful, edematous, often crusted or hemorrhagic vesicles, pustules or erosions. Umblicated vesiculopustules progress to punched-out erosions. Skin biopsy shows changes characteristic of herpes virus infection, such as multinucleated epithelial cells and ballooning degeneration of keratinocytes.¹⁰ Superficial granulomatous pyoderma is a rare variant of pyoderma gangrenosum. Lesions usually appear as a single, well-defined non-tender, superficial ulcer with exophytic or vegetating clean granulations.¹¹ Histopathologically, there is reactive epidermal hyperplasia accompanied by neutrophil-rich inflammation and focal granuloma formation. The ulcers show a characteristic layered granuloma. However in our patient, the distribution and multiplicity of the lesions, painful feature and histologic findings of eosinophil-rich vasculitic change, tissue eosinophilia favor necrotizing eosinophilic folliculitis rather than superficial granulomatous pyoderma or pyoderma gangrenosum. Halogenoderma is characterized by vesicular, pustular, hemorrhagic, ulcerative lesions but is usually not confined to the face. In histopathology, pseudo-epitheliomatous hyperplasia is observed and often, intraepidermal abscesses form with neutrophils and eosinophils.¹⁰ However, exposure history to halogen-containing drugs or substances is necessary.

The histological findings were the ultimate key to diagnosis, but even after diagnosis it was still challenging to choose a treatment that would minimize skin scarring and terminate the inflammatory process. Treatment with dapsone, prednisone, cyclophosphamide, indomethacin and cephalexin has been reported to be successful for necrotizing eosinophilic folliculitis.⁶ Our patient showed rapid response to systemic steroid and dapsone therapy.

Conclusion

There have been worldwide reports of RCD. Clinicians should be aware that besides the well-known features of RCD, such as maculopapular rash or eczema, necrotizing eosinophilic folliculitis may occur after Rhus contact or consumption. Careful clinicopathological correlation is needed for prompt diagnosis and proper treatment to reduce patient discomfort and skin scarring.