Review article CED

Clinical and Experimental Dermatology

CPD

Systematic review of the diagnosis of scabies in therapeutic trials

M. J. Thompson,1 D. Engelman,2,3 K. Gholam,4 L. C. Fuller5,6 and A. C. Steer2,3
1
Department of Paediatrics and Child Health, Western Australia Country Health Service, Kimberley Region, Australia; 2Department of Paediatrics, Centre
for International Child Health, University of Melbourne, Melbourne, Australia; 3Group A Streptococcal Research, Murdoch Childrens Research Institute,
Melbourne, Australia; 4Dermatology Department, Great Ormond Street Hospital, London, UK; 5International Foundation for Dermatology, London, UK;
and 6Department of Dermatology, Chelsea and Westminster NHS Foundation Trust, London, UK

doi:10.1111/ced.13152

Summary Human scabies (infestation with the mite Sarcoptes scabiei var hominis) causes a signifi-
cant disease burden worldwide, yet there are no agreed diagnostic guidelines. We
aimed to determine whether a consistent approach to diagnosing scabies has been
used for published scabies therapeutic trials. The data sources used were the MEDLINE,
Embase and Cochrane databases, from 1946 to 29 August 2013. Eligible studies were
trials of therapeutic interventions against scabies in human subjects, published in Eng-
lish, enrolling patients with scabies, and using various therapeutic interventions. Lan-
guage was a limitation of this study as some relevant trials published in languages
other than English may have been excluded. Each study was reviewed by two indepen-
dent authors, who assessed the clinical examination and testing approaches used for
scabies diagnosis in the included studies. We found that of 71 included trials, 40
(56%) specified which clinical findings were used for diagnosis, which were predomi-
nantly rash, rash distribution, pruritus and mite burrows. Parasitological testing was
used in 63% of trials (n = 45) and was used more frequently in clinic-based than in
field studies. Nearly one-quarter of trials (24%, n = 17) did not define the diagnostic
method used. Overall, the diagnostic approaches were poorly described, prohibiting
accurate comparison of existing studies. This review further supports the need for con-
sensus diagnostic guidelines for scabies.

Introduction varies widely between and within populations,4,5

with high rates in the Pacific and up to 78% of
Human scabies is caused by infestation with the young children affected in one area of Central
mite Sarcoptes scabiei var. hominis, and is under- America.5,6 Confined residential settings such as
recognised as a public health problem, despite gener- orphanages, nursing homes, displacement camps or
ating a considerable global disease burden, affecting prisons may generate epidemics, when peak preva-
over 100 million people.1,2 Scabies predominantly lence may reach over 70%.7,8
affects marginalized groups and those that experi- The itch caused by scabies has a direct effect on
ence poverty and overcrowding,2 perpetuating quality of life, causing sleep loss and subsequent
inequity for vulnerable populations.3 Prevalence reduced productivity.9 Scabies is associated with bac-
Correspondence: Professor Andrew Steer, Centre for International Child terial skin infection, predominantly with Staphylococ-
Health, Royal Children’s Hospital Melbourne, Flemington Road, Parkville, cus aureus and Streptococcus pyogenes, which in turn
Victoria, 3052, Australia can lead to invasive bacterial disease.10,11 There are
E-mail: [email protected]
clear links between scabies and acute post-strepto-
Conflict of interest: the authors declare that they have no conflicts of coccal glomerulonephritis,10,11 and there are emerg-
interest. ing epidemiological links between scabies-associated
Accepted for publication 18 September 2016 pyoderma and acute rheumatic fever.12

ª 2017 British Association of Dermatologists Clinical and Experimental Dermatology (2017) 42, pp481–487 481
Diagnosis of scabies  M. J. Thompson et al.

Hyperinfestation (crusted or Norwegian scabies), usu- Methods

ally in the setting of immunological compromise, is
Using a systematic review approach, we searched for
associated with high mortality.13
studies of therapeutic trials for scabies (Fig. 1). We
Although there are a few national guidelines and
reviewed therapeutic trials rather than observational
diagnostic algorithms, there are no internationally
studies because we expected that treatment studies
agreed standards for the diagnosis of scabies infesta-
might have a higher level of precision and documenta-
tion, making epidemiological and therapeutic studies
tion of diagnostic definitions. Trials were not assessed for
difficult to interpret and compare. The presence of
bias because outcome measures were not examined.
only 10–15 adult female mites in classic infesta-
The MEDLINE, Embase and Cochrane databases were
tion14,15 makes direct observation challenging. Clini-
searched for trials between 1946 and August 2013,
cal identification of a burrow is pathognomonic, but
using the terms ‘scabies OR sarcoptes’ and ‘treatment
it may not be present or demonstrable in all
OR therapy’. All abstracts were examined for relevance
cases.16,17 Other scabies-associated skin lesions may
by one reviewer. Further relevant articles were identified
mimic a wide variety of dermatological conditions.
via review of reference lists. Studies that were not thera-
The gold standard of diagnosis is demonstration of a
peutic trials for scabies, were not human trials or were
live mite, eggs or faecal material (scybala) via skin
not available in English were excluded.
scraping methods, but false negatives are common3
Data were extracted from the final set of included
and present difficulties in using this test as a com-
articles by two independent reviewers, with any cod-
parative tool. Furthermore, such testing requires
ing conflicts resolved by a third party. Information
microscopy, and is not always practicable in all clin-
was recorded about the study population and the
ical or field epidemiology settings. Dermatoscopy or
country where the trial took place. Trials were defined
high-power epiluminescence microscopy has been
as clinic-based if they were conducted in an outpatient
shown to be an effective adjunct to clinical examina-
clinic or within a hospital, and field-based if they were
tion,18,19 but has not been widely adopted. Other
conducted in the community or in an institution; the
serological and molecular tests show promise, but
latter was defined as a camp, school, prison, orphan-
they are not yet sufficiently sensitive or widely avail-
age, aged care facility or homeless shelter. A resource-
able to enable regular human use.20,21
limited country was defined as a country within the
To enable research collaboration and comparison, a
lower three categories of the 2013 United Nations
consistent diagnostic approach is required.1 We con-
Human Development Index.22
ducted a systematic review of diagnostic methods and
criteria used in therapeutic trials for scabies.

Figure 1 Systematic review flowchart.

482 Clinical and Experimental Dermatology (2017) 42, pp481–487 ª 2017 British Association of Dermatologists
 Diagnosis of scabies  M. J. Thompson et al.

Data relating to how scabies was diagnosed were Table 1 Trial setting and population characteristics.
extracted from the Methods section of all articles. Rash Study characteristics (N = 71) n %
characteristics and distribution were captured, and tri-
als listing rash distribution as ‘classic(al)’, ‘typical’, or Location
Field 23 32
‘sites of predilection’ without further definition were
Clinic 42 59
grouped together under ‘classic distribution’. Those tri- Unspecified 6 8
als that did not define the methods used for diagnosing Resource-limited country 53 75
scabies, for example stating, ‘patients with scabies were Vulnerable group 31 44
enrolled’, were classified as ‘unspecified’. The use of Institution 16 23
Age group
magnification was also captured, and included formal
All ages 37 52
epiluminescence microscopy and use of a hand lens. Adults only 18 25
Data regarding testing for scabies were also extracted Children only 13 18
from the Methods section of each article. Trials that Unspecified 3 4
reported ‘parasitological confirmation’ without further
detail were coded as using testing. A skin scraping was
defined as a scraping of the epidermis with a scalpel and
Table 2 Clinical features used to diagnose scabies.
microscopy of the resultant sample; studies that
described alternative extraction methods were coded Percentage of:
separately. The method of sample processing was
Trials using clinical
recorded. Findings for a positive microscopy result were All trials examination
divided into either mite identification (visualization of Clinical feature n (N = 71) (N = 40)
an adult or larval mite) or product identification
Unspecified clinical examination* 31 44 –
(defined as either scybala or mite eggs), or both.
Pruritus
Summary statistics and combinations of clinical Any 28 39 70
diagnosis and testing were calculated using Excel for Nocturnal 18 25 45
Mac 2011 (v014.4.3; Microsoft Corp., Redmond, WA, Rash
USA). Associations between the trial characteristics Any 40 56 100
Burrows 22 31 55
and the study’s diagnostic approach were examined
Papules 20 28 50
using v2 testing (SPSS software v20.0; IBM, Armonk, Nodules 9 13 23
NY, USA). Our results are reported according to Vesicles 12 17 30
PRISMA guidelines.23 Pustules 8 11 20
Excoriation 6 8 15
Rash distribution
Results Any 30 42 75
Classic 16 23 40
We initially identified 239 articles, with 71 meeting Contact history 16 23 40
inclusion criteria (Fig. 1). Trials were predominantly Magnification 5 7 13
clinic-based (n = 42, 59%), and just over half the
*Refers to articles that did not provide any details regarding
trials included all age groups (n = 37, 52%; Table 1). clinical examination findings used to diagnose scabies.
Three-quarters of the trials were conducted in
resource-limited countries (n = 53), with 55% of these
in a field setting (n = 29). distribution detailed in one study.24 Although 23%
Only 40 trials (56%) specified what clinical findings (n = 16) of all studies nominated ‘classic’ rash distri-
were used for diagnosis of scabies (Table 2). Of these, bution as part of the diagnosis, there was variation in
the predominant features mentioned as part of the the actual sites of rash used, with several studies not
diagnostic process were rash (n = 40, 100%), rash dis- defining the relevant body locations, while other stud-
tribution (n = 30, 75%), pruritus (n = 28, 70%) and ies specified up to 15 sites.25 Body diagrams, clinical
mite burrows (n = 22, 55%). Magnification was used photography and severity scales were used as adjuncts
to assist diagnostic examination in only 5 of all 71 to clinical assessment in a number of trials; however,
trials (7%). these tools were used as case or severity descriptors,
A number of studies required several clinical fea- rather than contributors to the diagnosis.
tures to be present for a diagnosis to be made, with up Although 45 trials (63%) conducted parasitological
to 12 characteristics of rash appearance and tests, not all used this information for diagnosis

ª 2017 British Association of Dermatologists Clinical and Experimental Dermatology (2017) 42, pp481–487 483
Diagnosis of scabies  M. J. Thompson et al.

Table 3 Testing approaches used. diagnostic criteria. Nearly a quarter of trials did not
Percentage of:
describe any aspect of how the diagnosis of scabies was
made. Slightly over half of the trials clarified their clini-
All trials Trials using cal diagnostic criteria, predominantly using rash, rash
Testing approach n (N = 71) testing (N = 45) distribution, pruritus and the presence of mite burrows.
Any testing for parasite 45 63 – Similarly, just over half of all of trials used parasitologi-
Testing for diagnostic purposes 40 56 89 cal testing for diagnostic purposes. Of the trials that did
Positive test required for diagnosis 23 32 51 specify the features used for diagnostic decision-making,
Skin scraping
features were frequently described vaguely, prohibiting
Performed* 39 55 87
Processing method† 8 11 18
confident interpretation of the methods used. The wide
Mite identification‡ 38 54 84 variation in definitions of rash characteristics and distri-
Mite product§ 27 38 60 bution further impeded trial comparison.
No predominant combination of diagnostic criteria
*A skin scraping was specified as the type of test performed;
†indicates that the report described that trial’s method of process- emerged through the review. It was often unclear
ing the skin scraping sample; ‡adult or larval mite forms were whether all diagnostic features were required to meet
accepted for a positive skin scraping result; §ova or scybala were case definition criteria or whether cases with fewer
accepted for a positive skin scraping result. features were included. Likewise, where testing was
used, it was often not performed for all subjects or was
(Table 3). Only 23 (51%) of those that did perform not a required feature for diagnosis.
testing required a positive test for diagnosis. Skin Our findings are in keeping with those of Leung
scrapings were the predominant form of testing speci- et al.,26 whose review of the evidence behind diag-
fied in 39 trials (87%), and only 8 (18%) described nostic methods for scabies concluded that diagnosis
their sample processing method. is often ‘imprecise and speculative’. Our study also
In combining the diagnostic aspects used, 26 trials overlaps with the 2007 Cochrane review of scabies
(37%) specified both clinical and testing approaches in treatment,27 which reported that all 22 included tri-
order to reach the diagnosis of scabies. Some trials als used a clinical diagnosis of scabies, but did not
specified only ‘clinical examination’ (n = 14, 20%), or examine this diagnostic process. There was parasito-
‘testing’ (n = 14, 20%) aspects. The remaining 17 tri- logical confirmation in 33.7% of included partici-
als (24%) did not describe any specific clinical or test- pants (903 of 2676), supporting our finding that
ing aspects. this is not a consistent feature used for diagnosis.
Of the 42 clinic-based trials, 27 (64%) used par- The observed difference in diagnostic approaches in
asitological testing as a component of diagnosis, field versus clinic settings is in keeping with the prag-
compared with 9 (39%) of 23 field trials matics of available resources. This presents a challenge
(P = 0.07). A higher proportion of studies that for guideline development, as a single approach may
involved all age groups (60%) used testing com- not suit each research or clinical environment. Diag-
pared with studies of children (31%; P = 0.11). nostic guidelines must be practical in a low-resource
There was no difference in the proportion of trials clinical setting, while maintaining diagnostic rigour.
in resource-limited and non-resource-limited coun- The development of point-of-care serological testing
tries that used testing (56% versus 57%, may improve diagnostic confirmation; however, such
P = 0.94), nor was there a difference between testing must be accurate, straightforward and
studies published since 2000 (61%) and those pub- cost-effective.
lished earlier (50%, P = 0.47). Our review is limited by including articles pub-
Only 10 studies (14%) provided a reference for the lished in English only. Additionally, we extracted
diagnostic approach used. These included skin scrap- only the diagnostic information that was clearly sta-
ing methods, rash appearance in children, or broader ted in the Methods sections of articles, and dis-
descriptive references. counted suggested or implied terms mentioned
elsewhere within the reports. Further, we reviewed
therapeutic trials and did not include epidemiological
Discussion studies. However, a recent a systematic review of
In this systematic review of scabies therapeutic trials, scabies prevalence observed a similar lack of diag-
we found that most studies used poorly defined nostic clarity in included studies.5

484 Clinical and Experimental Dermatology (2017) 42, pp481–487 ª 2017 British Association of Dermatologists
 Diagnosis of scabies  M. J. Thompson et al.

The high burden of disease caused by scabies,5 the • There were no consistent criteria used for diag-
increasing recognition of its serious complications,1,28 nosis in the therapeutic trials for scabies.
and the availability of highly effective antiscabetic • This review supports the need for the develop-
therapies27,29 all provide impetus for the development ment of consensus scabies diagnostic guidelines
of new control approaches. There is a pressing need to enable research aimed at controlling this
for consensus diagnostic criteria to enable accurate disease.
comparison of epidemiological data and assessment of
treatment methods. The development of diagnostic
guidelines through a recognized consensus process has
been initiated by the International Alliance for the
Control of Scabies.1,5 These guidelines will provide a
References
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2 Vos T, Flaxman AD, Naghavi M et al. Years lived with
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Diagnosis of scabies  M. J. Thompson et al.

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CPD questions (d) Dermoscopy.

(e) Microscopy of skin scrapings.
Learning objective
To appreciate the challenges in diagnosing scabies, in
Question 3
the context of the epidemiology, complications and
clinical signs of the disease. The complications of scabies can include which of the
following?
Question 1 (a) Impetigo.
(b) Invasive bacterial disease.
In which of the following groups is scabies most
(c) Local abscess.
prevalent?
(d) Post-streptococcal glomerulonephritis.
(a) Young children. (e) All of the above.
(b) Adolescents.
(c) Adults.
(d) Elderly people. Question 4
(e) People with suppressed immunity.
In this study, which of the following were the predom-
inant clinical criteria for diagnosis of scabies?
Question 2 (a) Rash and pruritus.
(b) Rash, pruritus and burrows.
Which of the following is the most specific test for sca-
(c) Pruritus and positive skin scrapings.
bies?
(d) Pruritus that is worse at night and an affected
(a) Clinical examination. family member.
(b) Serology. (e) There were no predominant clinical criteria found.
(c) PCR.

486 Clinical and Experimental Dermatology (2017) 42, pp481–487 ª 2017 British Association of Dermatologists
 Diagnosis of scabies  M. J. Thompson et al.

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(a) Axillary nodules. activity
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ª 2017 British Association of Dermatologists Clinical and Experimental Dermatology (2017) 42, pp481–487 487