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© 2009 The Author

JEADV

2009,

23

, 793–797 Journal compilation © 2009 European Academy of Dermatology and Venereology

DOI: 10.1111/j.1468-3083.2009.03177.x

JEADV

Blackwell Publishing Ltd

ORIGINAL ARTICLE

Variable response of crusted scabies to oral ivermectin: report on eight Egyptian patients

A Nofal*

Dermatology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt

*Correspondence:

A Nofal.

E-mail:

[email protected]

Abstract

Background

Several reports have proved the efficacy of oral ivermectin in the treatment of crusted scabies. However,

the response varied greatly between different studies.

Objective

The aim of this study was to evaluate the response of crusted scabies to oral ivermectin in eight Egyptian

patients.

Patients and Methods

Eight patients with crusted scabies, diagnosed clinically and confirmed microscopically, were

involved in this study. Patients received a single oral dose of ivermectin (200ug/kg) and re-examined at 2, 4, 6 and 8

weeks. A second dose of ivermectin was given in case of treatment failure at the end of the second week. A third dose

of ivermectin, combined with permethrin 5% and salicylic acid 5% was given at the end of the fourth week for the

nonresponders to the second dose.

Results

Two patients were completely cured after a single dose of ivermectin, 4 patients required a second dose at a

2-week interval to achieve cure and 2 patients cleared from scabies after the combined therapy. No recurrence was

reported at the end of 8 weeks. An inverse relation was observed between the response to ivermectin and the severity

of immunosuppression, crust thickness and mite burden.

Conclusion

Oral ivermectin is an effective alternative therapy for the treatment of crusted scabies. The response of

crusted scabies to oral ivermectin is variable and combination therapy with topical scabicides and keratolytics seems to

be the best choice.

Received: 1 October 2008; Accepted 9 December 2008

Keywords

crusted scabies, oral ivermectin, variable response

Conflicts of interest

None declared.

Introduction

Crusted scabies is a severe variant of scabies caused byhyperinfestation with the ectoparasite

Sarcoptes scabiei

. It ishighly contagious, has a high morbidity and may be associatedwith secondary bacterial infection.

1

Crusted scabies is characterizedby high mite burden, extensive hyperkeratotic scaling and crustedlesions, variable pruritus, and generalized lymphadenopathy,erythroderma and eosinophilia in some cases.

2,3

The increased incidence of crusted scabies, particularly amongpatients with HIV infection, the very frequent spread of scabies toclose contacts, and the frequent failures of topical scabicidesinitiate the efforts to find an effective alternative regimen forcrusted scabies.

4

Ivermectin is an antihelmintic agent similar to the macrolideantibiotics but without antibacterial activity. It has been used to

treat a variety of infestations in animals. In humans, ivermectinhas been proved effective in the treatment of onchocerciasis,strongyloidiasis, loiasis, bancroftian filariasis, and cutaneous larvamigrans. The safety of ivermectin has been demonstrated by itsextensive use against nematodes where the adverse effects wererare and minor.

5,6

There have been several reports of the successful use oforal ivermectin in the treatment of crusted scabies. However,the response varied greatly between different studies and thereis no definitive consensus on the optimal dosing regimen. Acomplete cure has been reported after a single dose, multipledoses and a combination therapy with topical antiscabetics andkeratolytics.

1–9

The aim of this study was to evaluate theresponse of crusted scabies to oral ivermectin in eight Egyptianpatients.

794

Nofal

© 2009 The Author

JEADV

2009,

23

, 793–797 Journal compilation © 2009 European Academy of Dermatology and Venereology

Patients and methods

Subject selection

The study included eight patients with crusted scabies who wereattending the Outpatient and Inpatient Clinics of Dermatology atZagazig University Hospitals, Zagazig, Egypt, during the periodfrom 15 May 2005 to 15 December 2006. Patients who had receivedany antiscabetic treatment in the previous month before enrolmentto the study, children weighing less than 15 kg, and pregnant andlactating women were excluded from the study. Crusted scabieswas diagnosed on clinical basis and confirmed microscopically bydemonstration of mites, eggs or faecal pellets in the skin scrapings.Severity of mite infestation was graded according to the numberof mites per field into mild (1–5), moderate (6–10) and severe(> 10). Before treatment, a thorough history taking and detailedsystemic and dermatologic examinations were done. The intensityof pruritus was recorded and secondary infection, if present, wastreated before the start of the study. Written consent was obtainedfrom all patients after they have been informed about the detailsof the study.

Drug administration

Ivermectin was administered under supervision as scored 6-mgtablets at a dose of 200

μ

g/kg body weight. People known to be inclose contacts with the patients were given oral ivermectin by thesame dose to minimize the risk of reinfestation. Patients weregiven standard instructions to prevent fomite transmission byhigh temperature laundering of all infested clothes and bedding.They were also advised not to use any topical antiscabetic, unlessprescribed, during the study period. No restriction, however, wasadvised concerning the use of medications required for treatmentof the underlying diseases. Routine laboratory tests were donebefore, during and after ivermectin therapy.

Evaluation and follow-up

All patients were evaluated at regular intervals of 2, 4, 6, and8 weeks for clinical and microscopical cure. Patients wereconsidered cured if at the end of 2 weeks there were no pruritus,no clinical evidence of scabies and no positive signs of skinscrapings. A second dose of ivermectin was given at the end of thesecond week in case of treatment failure, which was defined aspersistence of pruritus, clinical signs or microscopical evidence ofscabies. A third dose of ivermectin, combined with permethrin 5%and salicylic acid 5% was given at the end of the fourth week forthe non-responders to the second dose.

Results

Eight patients (5 women and 3 men) were included in the presentstudy. Their ages ranged from 25 to 78 years. They presented withdifferent severities of itching immunosuppression, mite infesta-tion and crust thickness (Table 1). Erythroderma, generalizedlymphadenopathy, secondary infection and eosinophilia were

found in 1, 2, 3 and 4 patients, respectively. Prior therapy wasreported in 6 patients; sulphur in 1 patient, crotamiton in 1 patientand permethrin in 4 patients. The response to oral ivermectin wasvariable. By the end of the second week, after a single dose of oralivermectin, 2 patients (nos 4, 5) were completely cured (Fig. 1)

Figure 1 Mild crusted scabies (case no. 4). (a) Before treatment. (b) After treatment with single dose of ivermectin.

Efficacy of oral ivermectin in crusted scabies

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© 2009 The Author

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2009,

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, 793–797 Journal compilation © 2009 European Academy of Dermatology and Venereology

and 6 patients showed minor or partial improvement of clinicalsigns of scabies and still had positive skin scrapings. After the seconddose of ivermectin, 4 patients (nos 1, 2, 6, 7) became completelycured by the end of the fourth week and the other 2 patients (nos3, 8) achieved complete cure by the end of the sixth week after athird dose of ivermectin combined with the topical therapy(Fig. 2). By the end of the last visit at 8 weeks, all patients were freeof scabies both clinically and microscopically without evidence ofrelapse or reinfestation. No major adverse effects or changes in thelaboratory data were reported after ivermectin therapy.

Discussion

Scabies represents a challenge to physicians, both in their choiceof optimal treatment which remains to be determined and in thecommunity-based epidemics. These issues are of greater concernwhen dealing with crusted scabies, particularly in immuno-suppressed individuals.

4

Although conventional topical agents are effective in the man-agement of classical scabies, they are less successful in treating themore severe variant, crusted scabies. This may be attributed to thehigh mite burden reported in these patients, inadequate applicationdue to non-compliance, difficulties in treatment of close contacts,variable penetration of the heavy crusts and emergence of resistanceresulting from extensive use of these preparations.

4,10,11

Several clinical trials have proved the efficacy of oral ivermectinin the treatment of crusted scabies.

1–9

Hence, it was consideredworthwhile to generate more data regarding the human use of oralivermectin in the treatment of crusted scabies, particularly thepossible factors that could modify its efficacy.

The results of the present study showed that two patients werecompletely cured after a single dose, four patients after 2 doses,and two patients after 3 doses combined with permethrin 5% andsalicylic acid 5%. These results were in accordance with thosereported by many authors. Some have shown complete cure of

Table 1 Summary of the studied patients

Case Age (year)

Sex Duration Pruritus Underlying immunosuppression

Crust thickness

Infestation Response to ivermectin

1 43 Female 2 months Mild Steroids for SS Moderate Mild After 2 doses

2 41 Female 4 months Moderate Steroids for PV Severe Moderate After 2 doses

3 55 Male 6 months Mild KS, HIV, Ch Severe Severe After 3 doses + TT

4 25 Female 1 month Moderate Steroids for SJS Mild Mild After single dose

5 32 Female 2 months Moderate Apparently healthy Mild Mild After single dose

6 58 Male 5 months Absent KS, Ch Moderate Moderate After 2 doses

7 78 Female 3 months Moderate Apparently healthy Moderate Moderate After 2 doses

8 53 Male 3 months Severe Leukaemia, Ch Severe Severe After 3 doses + TT

Ch, chemotherapy; KS, Kaposi sarcoma; PV, pemphigus vulgaris; SJS, Steven–Johnson syndrome; SS, systemic sclerosis; TT, topical therapy.

Figure 2 Severe crusted scabies (case no. 3). (a) Before treatment. (b) After treatment with three doses of ivermectin combined with permethrin 5% and salicylic acid 5%.

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© 2009 The Author

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2009,

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, 793–797 Journal compilation © 2009 European Academy of Dermatology and Venereology

their patients after a single dose,

1,3–5

others reported eradication ofcrusted scabies after multiple doses,

1,2,5,12–16

and many consideredthe combination therapy to be the best choice for treatment ofcrusted scabies.

2,4,5,9,17–23

In this study, the response to oral ivermectin was variable. Thismay be explained by the differences in the severity of immuno-suppression that would modify the host response to the mite and,consequently, the efficacy of ivermectin and the severity ofinfestation. The higher the mite burden, the difficult is the eradicationof scabies, the thickness and extent of the crusts that may interferewith adequate penetration of ivermectin, and the adherence totreatment protocols that might help to prevent reinfestation andtreatment failure.

Crusted scabies results from a failure of the cell-mediatedimmune response to control the proliferation of the scabies miteresulting in hyperinfestation. It is usually reported in associationwith an underlying immunosuppression, either due to diseases ordrugs.

9

The severity of immunosuppression may be determinedby the severity of the underlying cause as in the case of HIV infectionwith marked reduction of CD4 T lymphocytes, the duration ofimmunosuppression and the number of the immunosuppressiveagents. The more severe the immunosuppression, the higher is themite burden that makes eradication of scabies by oral ivermectinmore difficult. In the present study, the most severe immunosup-pression and the highest mite burden were present in the thirdand eighth cases and, hence, cure was only achieved after 3 dosesof oral ivermectin combined with the topical therapy. On theother hand, mild immunosuppression and mild infestation wereobserved in case no. 4 who presented by Steven–Johnson syndromeand received systemic steroids for 1 month only before gettinginfection; therefore, her crusted scabies was cured after a singledose of oral ivermectin. Case nos 1, 2 and 6 who achieved completecure after 2 doses of ivermectin were more or less intermediate inthe severity of immunosuppression and heaviness of infestationbetween the previous extremes.

Crusted scabies has also been reported in people withoutevident immunosuppression,

1,9

probably due to the presence of anunidentified immune defect that predisposes them to hyper-infestation by the scabies mite.

9

This finding was also observed intwo patients of the present study. The first one (case no. 5) presentedwith a mild form of crusted scabies (mild crust thickness andmild infestation) and she was cured after a single dose of oralivermectin. The second one (case no. 7) was the oldest patient in thestudy (78 years) and her crusted scabies, which was of a moderateseverity, cleared after 2 doses of ivermectin. The high degree ofskin dryness present in the elderly that leads to poor sebumsecretion of the lipophilic ivermectin to the skin surface, where theimmature mites take the drug,

24

may also explain the delayedresponse in the second patient.

Crust thickness and extent, by interfering with ivermectin’sadequate penetration, can modify patients’ response to this drug.Oral ivermectin has a half-life of 16 h. If thick crusts have developed,

then ivermectin in the blood will not profuse adequately to kill allthe mites. Because of these concerns, the concomitant use oftopical scabicides and keratolytics has been recommended toallow better penetration and to ensure maximum concentrationof the scabicide into the skin, thus adding to the beneficial effect ofivermectin.

5,25

This observation was also reported in two patients ofthis study (nos 3, 8), who presented with extensive widespreadcrusted lesions and achieved complete cure only after the additionof topical therapy to the third dose of ivermectin.

Adherence to the treatment protocols may also affect theefficacy of ivermectin in treatment of crusted scabies. Therefore,inadequate treatment of the close contacts, improper disinfectionof infested clothes and bedding, and inadequate trimming of nails,which harbour many mites, could allow a continuous source ofthe parasite, leading to treatment failure and reinfestation.

11

No major adverse effects were reported in the studied patientsafter ivermectin therapy. One patient complained of gastric upsetand two patients experienced a transient increase of pruritus,which could be attributed to skin reactivity against

Sarcoptes

antigens released after death of the parasite by ivermectin. Thiswas in agreement with the recorded safety after its extensive use inonchocerciasis and stronglyoidiasis.

5

However, its safety inchildren weighing less than 15 kg and in pregnant and lactatingwomen is not yet established. This restriction is based on theability of ivermectin to potentially cross poorly developed blood–brain barriers.

26

Another restriction was related to the concernsabout the excess risk of death in elderly patients.

27

However, thisrisk has not been confirmed.

2,10

Recently, emerging resistance toivermectin in humans has been reported.

28–30

Conclusions

Oral ivermectin is an effective alternative therapy for thetreatment of crusted scabies. The response of crusted scabies tooral ivermectin is variable. Precise evaluation of the severity ofimmunosuppression, crust thickness and mite burden may helpto choose the appropriate regimen for each individual case.However, in the absence of strict guidelines for the optimum useof ivermectin in the treatment of crusted scabies, it is stronglyrecommended to start with the combination therapy to achievethe maximum response against this debilitating, highly infectiousdisease.

Further studies are needed to define clearly the place of oralivermectin in the treatment of crusted scabies. The optimaldosage, the number of doses, the interval between doses, theefficacy against different stages of scabies mite, definite criteria ofcure and the risk of resistance with the extensive use are amongquestions that await answers in order to optimize ivermectintherapy for the treatment of crusted scabies.

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