992 Correspondence
important dermoscopic feature for the clinical and noninvasive
Fig 1. Dermoscopic image of tungiasis showing the ‘whitish chains’
(original magnification · 10).
bag surfaced and dermoscopy helped to visualize eggs in it.
We recently observed a case of tungiasis that complements the
dermoscopic aspects described by Cabrera and Daza.
A 31-year-old woman presented to our clinic with a painful
yellowish papule on the nail fold of her right first toe. One
week before, she had spent some days of vacation on a Brazil-
ian beach. On dermoscopy, the papule showed the typical
brownish opening of the flea on the periungual area. In the
central area, it was possible to visualize grey-blue blotches and
a large number of whitish oval structures linked together
forming a chain-like picture, in the abdomen of the flea. Sev-
eral extruded eggs could also be identified on the nail fold,
near the nail plate (Fig. 1).
In the present case, Tunga penetrans has burrowed in the peri-
ungual area, which is one of the typical sites for its penetra-
tion into the skin. Toes and periungual areas are reported to
be the sites of predilection in 73% of cases.2 The periungual
fold is a very narrow anatomical region, thus preventing the
flea from penetrating deeply, but allowing it to grow towards
the lateral aspect of the toe. This situation permitted not only
observation of the typical brownish-pigmented rings described
by Bauer et al.3 (although not centrally distributed) and the
grey-blue blotches described by Di Stefani et al.,4 but also visu-
alization, on dermoscopy, whitish structures in a chain-like
distribution, perfectly matching, in vivo, the image of the eggs
contained in the jelly-bag described by Cabrera and Daza, even
before any invasive attempt to remove the flea. This image
corresponds to the late stage of maximal growth of the flea,
corresponding to stage 3B of the evolution of the parasite, as
reported by Eisele et al., the moment when expelled eggs are
visible.5
Tungiasis is a benign and self-limited parasitic disease;
however, its correct diagnosis may prevent possible morbidi-
ties like abscesses, cellulitis, erysipelas and septicaemia. Dermo-
scopy has been shown to be an important and practical tool
for this purpose. In addition to the previous reports, we
would like to add the finding of ‘whitish chains’ as a further
Journal Compilation  2008 British Association of Dermatologists • British Journal of Dermatology 2008 159, pp979–995
diagnosis, in vivo, of tungiasis.
Department of Dermatology, Hospital R.M. BAKOS
de Clı́nicas de Porto Alegre, Universidade L. BAKOS
Federal do Rio Grande do Sul, Rua Coronel
Bordini 889, Porto Alegre RS 90440-001, Brazil
E-mail: renato@clinicabakos.com.br
References
1 Cabrera R, Daza F. Tungiasis: eggs seen with dermoscopy. Br J
Dermatol 2008; 158:635–6.
2 Muehlen M, Heukelbach M, Wilcke T et al. Investigations on the
biology, epidemiology, pathology and control of Tunga penetrans in
Brazil. II. Prevalence, parasite load and topographic distribution of
lesions in the population of a traditional fishing village. Parasitol Res
2003; 90:449–55.
3 Bauer J, Forschner A, Garbe C, Röcken M. Variability of dermoscopic
features of tungiasis. Arch Dermatol 2005; 141:643–4.
4 Di Stefani A, Rudolph CM, Hofmann-Wellenhof R, Müllegger RR.
An additional dermoscopic feature of tungiasis. Arch Dermatol 2005;
141:1045–6.
5 Eisele M, Heukelbach M, van Marck E et al. Investigations on the
biology, epidemiology, pathology and control of Tunga penetrans in
Brazil. I. Natural history of tungiasis in man. Parasitol Res 2003;
90:87–99.
Key words: dermoscopy, tungiasis, whitish chains, zoonosis
Conflicts of interest: none declared.
Indeterminate results on the interferon-c
release assay for tuberculosis screening
should not be ignored
DOI: 10.1111/j.1365-2133.2008.08792.x
SIR, We read with interest the recent report by Desai et al.1
comparing the QuantiFERON-TB Gold (QFT-G; Cellestis Ltd,
Carnegie, Vic., Australia) and the Mantoux test in tuberculosis
screening for candidates embarking on antitumour nec-
rosis factor (TNF)-a therapy. QFT-G and the other two com-
mercially available interferon-c release assays (IGRAs),
T-SPOT.TB (T-SPOT; Oxford Immunotec Ltd, Oxford, U.K.)
and QuantiFERON-TB Gold-In-Tube (QFT-IT; Cellestis Ltd),
work on the rationale that T cells of previously sensitized
individuals produce the cytokine interferon-c on re-encounter-
ing the mycobacterial antigen, and represent a significant
advance in the domain of tuberculosis diagnostics. IGRAs are
increasingly finding favour in screening for latent tuberculosis
prior to initiation of biologics for psoriasis2 and for confirm-
ing the diagnosis of tuberculides.3
While they are to be congratulated on identifying a
previously bacille Calmette-Guérin-vaccinated individual with
a false-positive Mantoux test and thus saving the patient
 2008 The Authors

unnecessary chemoprophylaxis, we were intrigued that they
did not expand on the finding that three of 11 (27%) of their
patients had indeterminate QFT-G readings.
We believe that every attempt should be made to clarify the
reasons behind an indeterminate test result. An IGRA may be
indeterminate if the mitogen-positive control containing
phytohaemagglutinin-P, a potent T-cell stimulant, fails to yield
a response, either due to an inability of the immune system to
mount a T-cell response or to improper blood handling and
testing conditions. Conversely, a positive nil control or high
background interferon-c activity in the absence of an antigen
is also recorded as an indeterminate result. It is helpful to
report the control results as it can alert the clinician to an
immunosuppressive condition in the test subject or to techni-
cal errors in the assay.
The inordinately high figure in the study by Desai et al.1
surpasses the reported incidence of indeterminate results in
other studies: 5% in patients with rheumatoid arthritis during
infliximab therapy4 and 7Æ8% in patients with chronic liver
disease awaiting liver transplantation.5 Ferrara et al.6 found that
indeterminate results were even more common (21Æ4%) in
hospitalized patients, the majority of whom (38Æ2%) were on
immunosuppressive agents including cancer chemotherapy,
systemic steroids and anti-TNF-a therapy. The three patients
with indeterminate QFT-G results in the study by Desai et al.1
were receiving methotrexate, ciclosporin or a combination of
the two drugs. We postulate that immunosuppression from
these agents could have led to a lack of response to the
mitogen and an indeterminate reading.
The largest study on the use of the T-SPOT and QFT-IT in
screening patients with psoriasis for latent tuberculosis
employed a 3-month wash-out period for oral immuno-
suppressants.2 The QFT-IT is a new variant of the QFT-G that
uses precoated blood collection tubes and simplifies the blood
processing procedure. Interestingly, only one of 19 subjects
had an indeterminate reading on the QFT-IT. Patients with
psoriasis who require anti-TNF-a therapy are likely to be on
immunosuppressive agents and these issues raise concern
about the utility of the IGRAs in testing this cohort.
Although the studies comparing the T-SPOT and the QFT-G
test are limited, available data suggest that indeterminate
results are significantly more common with the QFT-G test.6,7
This may be due to inherent differences in their assay
techniques: the QFT-G measures the level of interferon-c in
the supernatant of antigen-stimulated cells, whereas the
T-SPOT detects individual reactive memory T cells out of the
250 000 peripheral blood mononuclear cells in each test
sample.
Currently, the U.K. Health Protection Agency recommends
discussing the indeterminate result with the laboratory
provider and retesting, should the clinical situation warrant
it.8 The U.S. Centers for Disease Control and Prevention state
that the follow-up for a patient with indeterminate results has
not been determined, and outlines the options as repeating
the IGRA with a new specimen, administering a tuberculin
skin test, or neither.9
 2008 The Authors
Journal Compilation  2008 British Association of Dermatologists • British Journal of Dermatology 2008 159, pp979–995
Correspondence 993
Further large-scale comparative studies and guidelines are
warranted in patients with psoriasis who are immunosup-
pressed from systemic therapy, to delineate the role of the
three IGRAs in screening for latent tuberculosis prior to the
administration of TNF-a inhibitors. We propose reporting
the mitogen and negative control results if an indeterminate
result is encountered. This would help the clinician to
distinguish between immunosuppression and a true negative
result, and would lead to a more informative test. Further-
more, this would reduce the number of patients with psoriasis
in whom biologic therapy is withheld or delayed due to an
indeterminate result.
H.H. OON
National Skin Centre, 1 Mandalay Road, W.S. CHONG
Singapore 208205, Singapore C.F. LIEW*
*Department of Medicine,
National University Hospital,
5 Lower Kent Ridge Road,
Singapore 119074, Singapore
E-mail: hazeloon@nsc.gov.sg
References
1 Desai N, Raste Y, Cooke NT, Harland CC. QuantiFERON-TB
Gold testing for tuberculosis in psoriasis patients commencing
anti-tumour necrosis factor a therapy. Br J Dermatol 2008; 158:
1137–8.
2 Balato N, Ayala F, Gaudiello F et al. Comparison of tuberculin skin
test and interferon-c assays in patients with moderate to severe pso-
riasis who are candidates for antitumour necrosis factor-a therapy.
Br J Dermatol 2008; 158:847–8.
3 Angus J, Roberts C, Kulkarni K et al. Usefulness of the QuantiFERON
test in the confirmation of latent tuberculosis in association with
erythema induratum. Br J Dermatol 2007; 157:1293–4.
4 Takahashi H, Shigehara K, Yamamoto M et al. Interferon gamma
assay for detecting latent tuberculosis infection in rheumatoid arthri-
tis patients during infliximab administration. Rheumatol Int 2007;
27:1143–8.
5 Manuel O, Humar A, Preiksaitis J et al. Comparison of Quanti-
FERON-TB Gold with tuberculin skin test for detecting latent tuber-
culosis infection prior to liver transplantation. Am J Transplant 2007;
7:2797–801.
6 Ferrara G, Losi M, Meacci M et al. Routine hospital use of a new
commercial whole blood interferon-gamma assay for the diagnosis
of tuberculosis infection. Am J Respir Crit Care Med 2005; 172:631–5.
7 Ferrara G, Losi M, D’Amico R et al. Use in routine clinical practice
of two commercial blood tests for diagnosis of infection with Myco-
bacterium tuberculosis: a prospective study. Lancet 2006; 367:1328–34.
8 Health Protection Agency. Health Protection Agency Position Statement on the
use of Interferon Gamma Release Assay (IGRA) tests for tuberculosis (TB). Draft
interim internal HPA guidance, October 2007. Available at: http://
www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1204186168242
(last accessed 17 June 2008).
9 Mazurek GH, Jereb J, LoBue P et al. Guidelines for using the Quanti-
FERON-TB Gold test for detecting Mycobacterium tuberculosis infection,
United States. MMWR Recomm Rep 2005; 54 (RR-15):49–55.
Key words: indeterminate, interferon-c release assay, QuantiFERON-TB Gold,
T-SPOT, tuberculosis, tumour necrosis factor inhibitor
Conflicts of interest: none declared.