British Journal of Dermatologg (1993) 129, 696-699.

Folliculitis in Down's syndrome

CM.KAVANAGH. J.P.LEEMING,* G.M.MARSHMAN, N.J.REYNOLDS AND J.L.BURTONDepartments of Dennatolofiy and 'Microbiology. Bristol Royal Infirmary, Bristol BS2 fiHW. U.K.

Accepted for publication 7 May 1993

Summary Twenty-two male and 20 female adults with Down's syndrome were examined. Ten ofthe men andtwo of the women had a follicular rash consistent with Mulassezia folliculitts. Oral itraconazoletreatment produced a significant improvement in the rash, accompanied by a decrease in the skinMalassezia count. Clinical relapse occurred when therapy was discontinued, and was accompanied byreturn of the Malassezia yeasts.

In 1978, Finn and colleagues described a distinctivefollicular dermatosis in 45% of male patients withDown's syndrome.' Although no mention was made ofthe possibie aetiology of this rash, they speculated that Itmight be a 'follicular variety of seborrhoeic dermatitis'.As their description of the rash was consistent with adiagnosis of Malassezia folliculitis, we undertook aclinical and laboratory study to investigate this possibi-lity, and also to assess the efficacy ofthe antifungal agentitraconazole in the treatment of this condition.

Methods

Patients

Twenty-two male and 20 female Down's syndrome (DS)patients, with an age range of 24-43 years (mean 29and 30 years, respectively) were examined. Thirty-sixwere institutionalized, and six lived with their parents orguardians. Patients with a follicular rash on the trunkwere included in the treatment trial if they were aged 1 f)years or older, and were not receiving phenytoin.antacids, H2 antagonists or anticholinergics. Ethicalpermission for the study was granted by the ethicalcommittees of all health authorities caring for thepatients.

Treatment trial

Patients fulfilling the entry criteria were treated withoral itraconazole 100 mg daily, for 14 days. Clinical andmicrobiological assessments of either the back or chest,(whichever was more severely affected at the time ofenrolment) were made before treatment, immediatelyafter treatment (week 2) and 2 and 6 weeks afterstopping treatment (weeks 4 and 8).

Clinical assessment

An objective assessment of tbe severity of the rash wasobtained by counting the papules and pustules in a 5 cm-area of the most severely affected skin. The clinicalimpressions of the severity of papulo-pustules. extent oferythema, degree of scaling, and overall severity wererecorded on 1 OO-mm visual analogue scales by the sameassessor at each visit.

Microbiological assessment

At the first visit, the contents of a lesion were expressedwith a comedone extractor and homogenized in 0-12 5ml phosphate-buffered 0 1 % Triton X-lOO solution. Ateach visit tbe scrub-wash procedure of Williamson andKligman^ was used to harvest micro-organisms from 5cm^ of the skin of the back (interscapular) or chest(sternum). Qutintitication of bacteria and yeast in wash-ings and homogenates was made by standard surfacedrop techniques on fresh blood agar (incubated aerobi-cally at 37°C for 2 days). Reinforced Clostridia! Agar(Oxoid) with 6 mg/I furazoiidone (incubated anaerobi-cally at 37''C for 6 days) and a selective Malasseziarecovery medium^ (incubated aerobicaliy at 34°C for 14days).

Statistics

Wilcoxon's signed-rank paired test was used for allstatistical comparisons. P-values indicate significantdifferences compared with baseline (week 0).

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FOLLICULITIS IN DOWN'S SYNDROME 697

Figure 1. An example of papular folliculitis on the upper back andshoulders of a male DS patient.

Results

Clinical data

Ten of 22 (45%) male and two of 20 (10%) femalepatients examined exhibited a papulo-pustular folliculi-tis. This predominantly involved the upper back, chestand. to a lesser extent, tbe umbilical region (Fig. 1). Themost severely affected site (the site selected for lesioncounts and microbiological analyses) was the chest inthree patients, including both female subjects, and theupper back in the remainder. Co-existing dermatosesincluded seborrhoeic dermatitis of the face and scalp(two patients), discoid eczema (two patients), acnevulgaris (two patients) and rosacea (one patient).Patients did not complain of any itching associated witbthe rash.

The papulo-pustular folliculitis showed statisticallysignificant overall clinical improvement over the 2-weekperiod of treatment with itraconazole 100 mg daily, butrapid relapse was observed when treatment was with-

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Figure 2. Overall severity in 12 patients with US, as recorded on a 1 OO-mm visual analogue scale. Results are meaniSRM. •P<0-05:" P < 0 0 1 .

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Figure 3. Papulo-pustular count/5 crir iirea in 12 patients with OS.measured from the upper back or sternum, over the 8-week studyperiod- Results are meaniSEM. "P<()Ol.

drawn (Fig. 2). The papulo-pustular count followed asimilar pattern (Fig. 3). as did erythema and scaling,although the latter was mild in all cases.

Microbiology

Malassezia furfur was isolated from only four of the 12lesions sampled. Coagulase-negative staphylococci were

698 G.M.KAVANAGH et til.

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Figure 4. NIalassezia fur\ur cimnl ubttiinod from skin surface washings.lU-sults arc mcaniSEM. *P<()-n5.

cultured Irom six of the lesion.s. propiunibiicteriii fromthree and micrococci from one. Potential follicularpathogens such as Stapbylococctts atireus and Gram-neyative rods were not isolated from iesions. but S.attrcus was consistently recovered from the skin wash-ings of two patients. One of these two patients failed torespond clinically to itraconazole treiitment.

A statistically signiticant reduction in M.fttrftir countsobtained from skin washings was observed after itraco-nazole treatment, but counts increased rapidly duringihe post-treatment period, in line with the clinicalobservations (Fig. 4). Papulo-pustules. scaling and ery-thema improved and relapsed in parallel, during andafter treatment. Itraconazole treatment had no signifi-cant impact on bacterial counts obtained.

Discussion

Malassczia (I'ityrosporuni) foMiculitis was first reported byWeary and colleagues in \^)M.^ in a patient whorepeatedly relapsed on receiving antibiotics. The condi-tion has subsequently been recognized by a n,umber ofgroups in both apparently immunocompetent'' andimmunocompromised" "* patients. The usual clinicalpresentation is a follicular, often pruritic. rash consistingof papules and pustules, but no comedones. The rash islocalized predominantly on the upper back, chest andshoulders. Intralbllicular yeast cells and parafollicularlymphocytic infiltrates have been observed histologi-caliy.^' Although Mahissezia furfur is a recognizedintrafollicular saprophyte.'"" it is implicated in the

pathogenesis of this disorder by its frequent presence Lnlesions in the absence of other likely pathogens, and bythe favourable response of the rash to a variety of anti-fungal treatments.'^-

The clinical appearance of the dermatosis we observedwas very similar to that reported by Finn and colleaguesin DS.' and was consistent with a diagnosis of MalasseziaIblliculitis. The absence of itching, a common presentingcomplaint in Malnssezia foliiculitis. might be explainedby psychological factors. The failure to isolate M. furfuror any other potential ibilicular pathogen from many ofthe expressed lesions was disappointing. Kowever M.ftirfur is notoriously difficult to cultivate, and it is possiblethat the viability of organisms in lesions might besubstantially reduced by the host response. The skinsurface M. furfur counts closely paralleled the clinicalresolution and subsequent relapse. Histological evidenceis not available, because biopsy was not consideredjustified in this group of patients.

A wide range of dermatoses have an increasedprevalence in patients with DS." These include sebor-rhoeic dermatitis, blepharitis, atopic dermatitis, tineapedis. cutis marmorata. and alopecia areata.'"* '̂ There issome evidence implicating M. furfur in the pathogenesisof each of the first three of these conditions."'"'** It islikely that the susceptibility of DS patients to foliiculitis isdue to some form of immunological deficit. Abnormali-ties in both cellular (lymphocyte) and humoral (IgG)function have been noted in DS.'"*-' and several immu-nocompromised groups have been reported to be suscep-tible to Malassezia foliiculitis.^ ** The mechanism wherebyimmunodeficiency might lead to M. /Nr/nr-media teddisease is uncertain, but the observation that Mtilasscziafoliiculitis can be caused by antibacterial therapy sug-gests that yeast population expansion might play a role.We found no evidence to support this idea, the meanpretreatment skin surface count of 3x 10-/cm- beingconsiderably lower than the mean value of approxi-mately l()'*/cm- found on both the upper back and chestin a previous study of young adults, using the same

Various topical preparations improve Malassczia folii-culitis. inciuding 2% selenium sulphide, 50% propyleneglycol, 2% salicylic acid, and econazole.''' Oral therapyhas been attempted with ketoconazole'- and isotreti-noin.-' but both produce side-effects. Itraconazole wasselected for this study on the basis of its favourable invitro activity against M.fttrfttr.-'^-'' its pharmacokinetics,and its safety. It is a lipophilic agent, and is excreted inrelatively high concentrations in sebum.^ However, withthe regimen selected, clinical response was not complete,

FOLLICULITIS IN DOWN'S SYNDROME 699

and both M. furfur counts and rash severity scoresrapidly returned to near pretreatment values aftertreatment ceased. Rapid relapse has also been reportedafter treatment of Malassczia foliiculitis with oral ketoco-nazole. which achieves much lower concentrations insebum.- but has slightly better activity against M. ftirfurin vitro.-^'* A higher dose (200 mg daily), or a longercourse of itraconazole may yield better results. In theabsence of satisfactory alternative oral agents, thesepossibilities are worthy of investigation in patients withsevere chronic or relapsing Malassezia foliiculitis.

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