J AM ACAD DERMATOL

VOLUME 64, NUMBER 5Letters 989

stimulation may contribute to the proinflammatoryvicious circle in these diseases.

In addition, there is the possibility that MDA5could act as an autoantigen in its own right. This is ofspecial interest in DM, where circulating anti-MDA5antibodies have been detected in a subset of pa-tients.1 These autoantibodies may bind basal MDA5-positive keratinocytes and in this way support thejunctional inflammation which is seen histologically.This assumption would agree with earlier observa-tions of immunoglobulin deposits along the basalmembrane, regularly found in the direct immuno-fluorescence staining of DM lesions.7

Subsequently, our observations reveal a potentialproblem in the standard diagnostic procedure ofautoimmune diseases: anti-MDA5 and a number ofother autoantibodies that are described in DM andrelated diseases (including anti-PM/Scl, anti-SSA/Ro,and anti-SSB/La) target proteins whose expression isstimulated by IFNs. However, in routine diagnostics,‘‘unstimulated’’ tissues are used for indirect immuno-fluorescence investigations to detect autoantibodiesin the sera (eg, HEp2 cells), and these tissues may notinclude an appropriate amount of the crucial anti-gens. It is tempting to speculate that an alternative useof IFN-treated tissues as a substrate could enhancethe diagnostic sensitivity of screening analyses. Thisview is supported by our results, which show asignificant difference in the MDA5-expression ofnormal and lesional ‘‘IFN-loaded’’ skin.

Sabine Zahn, PhD,a Winfried Barchet, PhD,b

Claudia Rehkamper,a Thorsten Hornung,a

Thomas Bieber, MD, PhD,a Thomas Tuting,MD,a and Jorg Wenzel, MDa

Department of Dermatology and Allergologya andthe Institute of Clinical Chemistry and ClinicalPharmacology,b University of Bonn, Bonn,Germany

Supported by a grant from the Deutsche For-schungsgemeinschaft DFG (WE 4428/1-1).

Conflicts of interest: None declared.

Correspondence to: Jorg Wenzel, MD, Departmentof Dermatology and Allergology, University ofBonn, Sigmund-Freud Str 25, 53105 Bonn,Germany

E-mail: joerg.wenzel@ukb.uni-bonn.de

REFERENCES

1. Sato S, Hirakata M, Kuwana M, Suwa A, Inada S, Mimori T, et al.

Autoantibodies to a 140-kd polypeptide, CADM-140, in Japa-

nese patients with clinically amyopathic dermatomyositis. Ar-

thritis Rheum 2005;52:1571-6.

2. Nakashima R, Imura Y, Kobayashi S, Yukawa N, Yoshifuji H,

Nojima T, et al. The RIG-I-like receptor IFIH1/MDA5 is a

dermatomyositis-specific autoantigen identified by the anti-

CADM-140 antibody. Rheumatology (Oxford) 2010;49:433-40.

3. Chistiakov DA. Interferon induced with helicase C domain

1 (IFIH1) and virus-induced autoimmunity: a review. Viral

Immunol 2010;23:3-15.

4. Wenzel J, Tuting T. An IFN-associated cytotoxic cellular immune

response against viral, self-, or tumor antigens is a common

pathogenetic feature in ‘‘interface dermatitis’’. J Invest Derma-

tol 2008;128:2392-402.

5. Patel VA, Lee DJ, Longacre-Antoni A, Feng L, Lieberthal W,

Rauch J, et al. Apoptotic and necrotic cells as sentinels of local

tissue stress and inflammation: response pathways initiated in

nearby viable cells. Autoimmunity 2009;42:317-21.

6. Kawai T, Akira S. The role of pattern-recognition receptors in

innate immunity: update on Toll-like receptors. Nat Immunol

2010;11:373-84.

7. Jones SA, Black MM. The value of direct immunofluorescence as

a diagnostic aid in dermatomyositis—a study of 35 cases. Clin

Exp Dermatol 1997;22:77-81.

8. Wenzel J, Worenkamper E, Freutel S, Henze S, Haller O, Bieber T,

et al. Enhanced type I interferon signalling promotes Th1-biased

inflammation in cutaneous lupus erythematosus. J Pathol

2005;205:435-42.

doi:10.1016/j.jaad.2010.08.004

Clinical utility of a commercially available PCRassay for common dermatologic skininfections

To the Editor: A majority of common skin infectionsare diagnosed in the clinical setting via history andphysical examination, with biopsies and culturesused for difficult cases. The sensitivity and specificityof so-called confirmatory tests are often relativelylow or poorly characterized.1

Polymerase chain reaction (PCR) assays have beenshown to be effective diagnostic tools for mucocuta-neous infections.2 Direct comparison of PCR withculture assays has shown PCR to be superior in bothsensitivity and specificity.3 Until recently, there hasbeen no commercially available assay that analyzesmultiple pathogens on one sample. A commerciallyavailable PCR assay (CAPA) has been shown to beeffective in screening for cervical and urethral path-ogens, but no studies addressing the utility of theseassays for skin infections were found.4 Over the past2 years, we have used a CAPA currently marketed togynecology practices (OneSwab; MDL Laboratories,Hamilton, NJ) to aid diagnosis of skin infections byaggressively rubbing the PCR swab across the top ofthe lesion.

Wepresent a reviewof our clinical experiencewiththis CAPA. After institutional review board approvalwas obtained, a retrospective medical record reviewwas performed at our outpatient clinic from January2008 through August 2010 for all patients who

Fig 1. Total number of patients that were tested using theCAPA was 127. A higher number of total cases (number ofindividual PCR assays) were examined because somepatients had more than one PCR performed. Total casesabstracted: 170; 88 excluded because of mucosal location(44), incomplete medical records (42) and because testswere run for screening purposes at patient’s request (2).Total number of cases included in sensitivity and specific-ity analysis was 82. Analysis showed 20 cases to be truepositives ( positive test result in patient with disease);1 false positive ( positive test result in patient withoutdisease); 7 false negatives (negative test result in patientwith disease); and 54 true negatives (negative test result inpatient without disease. Below each heading is the break-down of organisms that represented each category: HSV,herpes simplex virus 1 and/or 2; HPV, human papilloma-virus; MCV, molluscum contagiosum virus; VZV, varicellazoster virus; NG, Neisseria gonorrhoeae.

J AM ACAD DERMATOL

MAY 2011990 Letters

underwent CAPA testing. A ‘traditional’ diagnosis wasdeterminedby twophysicianswhowere blinded as tothe results of the CAPA (J. R. [ faculty dermatologist]and J. G. [resident physician]). Their diagnosis wasmade by using all other available information, includ-ing clinical history as well as biopsy and cultureresults. Exclusion criteria included 1) a site otherthan the skin (n¼ 44); 2) incomplete/missingmedicalrecords (n ¼ 31); 3) patients in whom the CAPA wasbeing used as a screening tool (testing performed at apatient’s requestwithout strong clinical suspicion, n¼2); and 4) patients forwhoma clinical diagnosis couldnot be agreed upon (n¼ 11). We then compared this‘traditional’ diagnosis with the CAPA results.

The skin infections tested are listed in Fig 1. Wefound 127 patients who had 170 PCR analysesperformed. Of these analyses, 82 met inclusioncriteria (see Fig 1). The overall sensitivity for theCAPA was 74.07% and specificity was 98.18%. Onefalse-positive was reported as Candida, although thepatient may have had a concurrent infection. False-negative results may have occurred because speci-mens were taken after viral shedding ceased. Ofnote, all the CAPAs were billed under $150, and theresults were available within 48 hours.

Unusual clinical presentations can pose difficultyin making rapid diagnoses which can lead to delayedtreatment.5 Since the current diagnostic ‘‘gold stan-dard’’ is a combination of a thorough history, phys-ical examination, and laboratory testing whenappropriate, an unmet need remains for a confirma-tory test with sufficient sensitivity and specificitywhen the diagnosis is under question. This workrecognizes such a confirmatory assay that is alsoconvenient and economically feasible. This type ofassay may decrease the need for invasive testing bydelivering prompt and reliable diagnostic informa-tion to augment traditional diagnostic methods.

Jennifer Gordon, MD,a Jason Reichenberg, MD,a

and Kimberly Carter, MDb

Department of Dermatologya and Department ofObstetrics/Gynecology,b University of TexasSouthwestern, Austin

Funding sources: None.

Conflicts of interest: None declared.

Correspondence to: JasonReichenberg,MD,Universityof Texas Southwestern: Austin, Department of Der-matology, 601 E 15th St, Austin, TX 78701

E-mail: jreichenberg@seton.org

REFERENCES

1. Schomogyi M, Wald A, Corey L. Herpes simplex virus-2 infection.

An emerging disease? Infect Dis Clin North Am 1998;12:47-61.

2. Strick LB, Wald A. Diagnostics for herpes simplex virus: is PCR

the new gold standard? Mol Diagn Ther 2006;10:17-28.

3. Schmutzhard J, Merete Riedel H, ZweygbergWirgart B, Grillner L.

Detection of herpes simplex virus type 1, herpes simplex virus

type 2 and varicella-zoster virus in skin lesions. Comparison of

real-time PCR, nested PCR and virus isolation. J Clin Virol

2004;29:120-6.

4. Adelson ME, Feola M, Trama JP, Tilton RC, Mordechai E. Simul-

taneous detection of herpes simplex virus types 1 and 2 by Real-

Time PCR and Pyrosequencing. J Clin Virol 2005;33:25-34.

5. Umstattd LJ, Reichenberg JS. Varicella pneumonia with immune

thrombocytopenic purpura: a patient with multiple complica-

tions. Cutis 2008;82:399-402.

doi:10.1016/j.jaad.2010.09.725