Clinicalknots

HIV associated eosinophilic folliculitis—diVerential diagnosis and management

Sara L Simpson-Dent, Louise A Fearfield, Richard C D Staughton

Eosinophilic folliculitis (EF) is a chronic, intensely pruritic condition of unknown pathogenesisthat causes marked morbidity in those HIV patients whom it aVects. There is a wide diVerentialdiagnosis of itchy skin conditions in HIV which are amenable to diVerent treatments. It is there-fore essential to take a biopsy of each suspected case and examine multiple sections of the biopsyto confirm or refute a diagnosis of EF. Treatment of EF can be diYcult but we hope that by sug-gesting a rational approach to this and considering possible therapeutic options more patientsmay be helped with this troublesome dermatosis.(Sex Transm Inf 1999;75:291–293)

Keywords: eosinophilic folliculitis; HIV

IntroductionEosinophilic pustular folliculitis was originallydescribed by Ofuji et al.1 It was not until 1986that it was first recognised to occur in thehuman immunodeficiency virus (HIV) in-fected population.2 In this group it is nowreferred to as HIV associated eosinophilicfolliculitis (EF) as it shows diVerences from theoriginal Japanese description in its distribution,appearance of lesions, disease course, andsymptoms. EF is not unique to HIV as it hasrarely been described in association withhaematological malignancies.3

Clinical picturePatients aVected by EF classically complain ofa persistent pruritic rash. The intensity of theitch is akin to that of scabies and patients exco-riate deeply. Clinically, one can see 2–3 mmerythematous papules or pustules, most fre-quently aVecting the shoulders, trunk, upperarms, neck and forehead, where it can bedisfiguring (fig 1). Less commonly, other areasof the body are aVected but EF is only rarelygeneralised. Lesions are follicular and are oftenmarkedly excoriated, making it diYcult todetermine their nature. It is therefore impor-tant to look for fresh unexcoriated lesions.There are no associated systemic features butpatients are often tired and irritable.

EF is quite common, occurring in HIVinfected individuals with a CD4 count of lessthan 250 ×106/l with an incidence, in one series,of 9%.4 Up to 50% of suVerers will have aperipheral eosinophilia, up to 4×109/l in ourseries and their IgE is often also elevated.

DiVerential diagnosisClinically the diVerential diagnosis of EF isbetween the infective folliculitides or otherdermatoses that may or may not be HIVrelated—for example, scabies, urticaria, drugrashes, and eczema. Clues in the history andthe examination can help refine the diagnosis(table 1). Of note we feel that it is inappropri-ate to make a diagnosis of papular eruption of

HIV as most cases will turn out to be EF ifinvestigated appropriately.

Investigation of EFOwing to the wide diVerential diagnosis of EFwe always recommend that a skin biopsy istaken and sent for histology for routine haema-toxylin and eosin stain as well as for specialstains for fungi, bacteria, and viruses, ascutaneous infections can present with atypicalclinical features. The biopsy should, if possible,be taken from an unexcoriated fresh lesion andserially sectioned. Sellotape strippings fordemodex mites and scrapings for scabiesshould also be performed if there is any clinicalsuspicion of these.

Figure 1 (A) Back of patient suVering from EF. Note themultiple excoriation marks. (B) Close up of a patient’sforehead demonstrating the characteristic erythematousfollicular papules of EF.

Sex Transm Inf 1999;75:291–293 291

Department ofDermatology, Chelseaand WestminsterHospital, LondonSW10 9NHS Simpson-DentL FearfieldR Staughton

Correspondence to:Dr Simpson-Dent.

Accepted for publication7 September 1999

Histology of EFThe histology of EF5 shows an inflammatoryinfiltrate, predominantly of eosinophils andlymphocytes which is folliculocentric withmarked sebaceous lysis (fig 2). This is distinctfrom infective causes of folliculitis—for exam-ple, Gram positive cocci, demodex, and pityro-sporum when micro-organisms are seen withinthe inflammatory infiltrate (macrophages andneutrophils). The aVected follicle is frequentlyruptured in a bacterial folliculitis. The histo-pathologist should be asked to take multipleserial sections of the EF biopsy as otherwise theaVected follicle may be missed and theincorrect diagnosis made.

Pathogenesis of EFThe pathogenesis of EF is unknown but, owingto the folliculocentric nature of the inflamma-tion, an opportunistic infection has been

proposed although no one organism hasconsistently been isolated in biopsy specimens.Fungi, yeasts, demodex, and bacteria have all attimes been seen and implicated. Other theoriesare of a follicular hypersensitivity reaction or anautoimmune reaction to sebum (L A Fearfield,in preparation).

Treatment of EFTreatment of EF is diYcult and varied becausethe underlying pathogenic mechanism of EF stillremains to be elucidated. Treatments tried haveincluded topical steroids, topical ascarides—forexample, permethrin, phototherapy (ultravioletA and B light), itraconazole, isotretinoin, andmetronidazole. All have had reported successesbut the series reported have tended to be ofsmall size and anecdotal rather than controlledor randomised. We discuss the diVerent modali-ties below and our recommendations for treat-ment are shown in table 2.

TOPICAL STEROIDS

These can give partial temporary symptomaticrelief but new lesions continue to crop up. Forexample, 0.1% betamethasone valerate (Betno-vate, Glaxo), can be useful as a temporary meas-ure when awaiting the results of the biopsy.

ANTIHISTAMINES

The anti-eosinophilic cetirizine (Zirtek,Schering-Plough) gives modest symptomaticrelief especially if higher than usual dosages areused—for example, 20–40 mg daily in divideddoses.

ULTRAVIOLET B PHOTOTHERAPY

Patients often report an improvement in symp-toms after sunny holidays abroad andultraviolet B is established as an eVectivetreatment.6 Patients mostly respond to thriceweekly broad band ultraviolet B within 3–6weeks. Relapse is frequent and weekly mainte-nance ultraviolet B may be needed. UltravioletB exerts an immunosuppressive eVect on theskin and herpes simplex virus is reactivated insome. Earlier fears of accelerating progressionof HIV disease have not been borne out.

ITRACONAZOLE

It has been suggested, by some authors, thatfungi or yeasts—for example, Pityrosporumovale may be involved in the pathogenesis ofEF. This is certainly supported by the responseof EF to oral itraconazole. In one study, byBerger et al, of 28 patients 74% showed initialcomplete or partial response to oral itracona-zole. At 3 months five remained clear oV treat-ment, two required topical steroids only, and12 were controlled (n=8) or partly controlledwith oral itraconazole.7 It is suggested that itra-conazole is started at a dose of 200 mg daily. Aresponse is normally seen within the first 2weeks but if this has not occurred or theresponse is incomplete then the dose may beincreased to 300 mg or 400 mg daily althoughthe incidence of side eVects is then increased.Maintenance therapy may be necessary. Fluco-nazole is not a substitute for itraconazole aspatients changed to this drug relapsed.7

Table 1 Ways of obtaining diagnosis of eosinophilic folliculitis

DiVerential diagnosis Clues in history and examination

Infestations:Scabies Nightime itching

Partner itchingGenital and web space lesions presentNo facial lesions

Papular urticaria(insect bite reactions)

Crops of linearly arranged papulesPets at home, hostel accommodation, or of no fixed abode?Lice on seams of patient’s clothes

Atopy:Urticaria Individual weals lasting 6–12 hoursEczema ?Family or personal history of atopy

Flexural rashIatrogenic:

Drug rash New drug within past 10–14 daysGeneralised rash

Other:Nodular prurigo Nodular rather than papular lesions lasting months/yearsLichen planus/nitidis Flat topped purple papules with Wickham’s striae

?Any buccal or genital lesions

Figure 2 Medium power of haematoxylin and eosin stainedsection showing an infiltrate of eosinophils and lymphocytescentred on the follicle with marked sebaceous lysis.

Table 2 Management of eosinophilic folliculitis

Short term management

(1) Biopsy, then while awaiting result:(2) Topical steroid—for example, 0.1% betamethasone valerate ointment(3) Antihistamine—for example, cetirizine 20–40 mg daily

Long term management

4 week trial of itraconazole 200 mg once dailyor

metronidazole 250 mg three times dailyor

referral to a dermatologist for ultraviolet B 2–3 times/week to clearance+/− maintenance

orisotretinoin 20–40 mg daily for 4–6 weeks

292 Simpson-Dent, Fearfield, Staughton

METRONIDAZOLE

Metronidazole 250 mg three times daily for 4weeks was reported to be eVective in clearingEF in five out of five patients initially8 and fol-lowing any subsequent relapse. This followedthe finding of a Gram negative organism onone of the patient’s biopsies.

ISOTRETINOIN

In an initial study in 19959 all of the sevenpatients treated demonstrated complete re-sponse within 1–4 weeks of starting isotretinointreatment at a dose of 40–80 mg/day (higherdoses were given for those patients who weremore severely aVected). Any relapses respondedto repeat courses of isotretinoin. (It must beremembered that isotretinoin is teratogenic andtherefore should be used only with extreme cau-tion in women of childbearing age.)

In our experience it is a very eVective andwell tolerated treatment using a lower dose of20 mg daily for 6–8 weeks. The usual side effectof drying of the skin can be counteracted by theliberal use of moisturisers. The mechanism ofaction may be to reduce perifollicular cellularinfiltration but the drug greatly curtails sebumproduction, which Fearfield has proposed asthe putative autoantigen in EF.

PERMETHRIN

The commensal follicle mite, demodex, is apossible trigger antigen. A small series ofpatients have responded to topical 5% per-methrin cream used daily on lesions and wereable to control the disease eventually with oneor two applications per week but uponcessation of treatment lesions recurred,10 butwe have been unable repeat such success.

ANTIRETROVIRAL THERAPY

We have seen a marked decrease in the numberof patients with EF in our clinics since the

introduction of highly active antiretroviraltherapy (HAART), although there have notbeen any reports of this in the literature. This isprobably because patients’ CD4 counts usuallyrise above 250 ×106/l on HAART.

OTHERS

Topical sodium cromoglycate, topical antibiot-ics, prednisolone, and dapsone have also beensuccessfully used in some patients.

Contributors: SLS-D wrote the paper; LAF performed theresearch project and provided references and clinical andhistopathological pictures; RCDS supervised the researchproject and the paper.

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7 Berger TG , Heon V, King C, et al. Itraconazole therapy forhuman immunodeficiency virus-associated eosinophilicfolliculitis. Arch Dermatol 1995;131:358–60.

8 Smith KJ, Skelton HG, Yeager J, et al. Metronidazole foreosinophilic pustular folliculitis in human immuno-deficiency virus type 1-positive patients. Arch Dermatol1995;131:1089–91.

9 Otley CC, Avram MR, Johnson RA. Isotretinoin treatmentof human immunodeficiency virus-associated eosinophilicfolliculitis. Arch Dermatol 1995;131:1047–50.

10 Blauvelt A, Plott RT, Spooner K, et al. Eosinophilic follicu-litis associated with the acquired immunodeficiencysyndrome responds well to permethrin. Arch Dermatol1995;131:360–1.

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