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   Table of Contents      
ORIGINAL ARTICLE
Year : 2022  |  Volume : 8  |  Issue : 2  |  Page : 158-162

False Positive Reaction to VDRL Test with Prozone Phenomenon in a Case of Lepromatous Leprosy


1 Department of Microbiology, Maulana Azad Medical College, New Delhi, India
2 Department of Dermatology & STD, Maulana Azad Medical College, New Delhi, India
3 Department of Medicine, Maulana Azad Medical College, New Delhi, India

Date of Submission10-Feb-2022
Date of Acceptance03-Apr-2022
Date of Web Publication11-Jul-2022

Correspondence Address:
Rohit Chawla
Postal Address: 4A/55, Old Rajinder Nagar, New Delhi-110060
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mamcjms.mamcjms_12_21

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  Abstract 


Abstract The venereal disease research laboratory (VDRL) test, a nontreponemal test for syphilis, may under a certain set of conditions give false positive results in patients who are not infected with Treponema pallidum. A false positive reaction is defined as a positive reaction to nontreponemal tests, and a negative reaction to treponemal tests, in the serum of a patient who has no history or clinical evidence of syphilis or other treponematosis. A prozone phenomenon in nontreponemal tests is seen largely with secondary syphilis due to high-titer samples that show nonreactive results unless the specimens are diluted. We report here perhaps the first case of lepromatous leprosy, which had a false positive reaction to the VDRL test with the prozone phenomenon. The case initially presented to the outpatient clinic with complaints of epistaxis with nasal stuffiness. The finding of septal perforation on nasal endoscopy is what led to the initial suspicion of syphilis and the subsequent syphilis workup. It was only when the false positive reaction to VDRL test with the prozone phenomenon was noted that the search for other causes was made, which eventually lead to the diagnosis of lepromatous leprosy.

Keywords: False positive reaction, lepromatous leprosy, prozone phenomenon, venereal disease research laboratory test


How to cite this article:
Chawla R, Thakur P, Mohan Kochhar A, Singla S. False Positive Reaction to VDRL Test with Prozone Phenomenon in a Case of Lepromatous Leprosy. MAMC J Med Sci 2022;8:158-62

How to cite this URL:
Chawla R, Thakur P, Mohan Kochhar A, Singla S. False Positive Reaction to VDRL Test with Prozone Phenomenon in a Case of Lepromatous Leprosy. MAMC J Med Sci [serial online] 2022 [cited 2022 Sep 26];8:158-62. Available from: https://www.mamcjms.in/text.asp?2022/8/2/158/354385




  Introduction Top


The venereal disease research laboratory (VDRL) test, a nontreponemal test for syphilis, may under a certain set of conditions give false positive results in patients who are not infected with T. pallidum.[1] A false positive reaction is defined as a positive reaction to nontreponemal tests, and a negative reaction to treponemal tests, in the serum of a patient who has no history or clinical evidence of syphilis or other treponematosis. These are categorized as either acute (occurring for <6 months) or chronic (occurring for >6 months). Chronic false positive reactions are associated with connective tissue disorders (e.g., systemic lupus erythematosus), intravenous drug use, malignancy, older age, and leprosy.[1] A prozone phenomenon in nontreponemal tests is seen largely with secondary syphilis due to high-titer samples that show nonreactive results unless the specimens are diluted.[2] We report here perhaps the first case of lepromatous leprosy, which had a false positive reaction to the VDRL test with the prozone phenomenon. The case initially presented to the outpatient clinic with complaints of epistaxis with nasal stuffiness. The finding of septal perforation on nasal endoscopy is what led to the initial suspicion of syphilis and the subsequent syphilis workup. It was only when the false positive reaction to VDRL test with the prozone phenomenon was noted that the search for other causes was made, which eventually led to the diagnosis of lepromatous leprosy.


  Case Report Top


A 61-year-old male patient, resident of New Delhi, presented in February 2019 to the outpatient clinic of a tertiary care hospital in New Delhi, India, with the chief complaints of epistaxis with nasal stuffiness for the past 7 months. He had no history of hypertension and diabetes mellitus. On examination, he had nasal crusting with swelling of the face and ears. Bilateral nasal packing was done and the patient was planned for nasal endoscopy. The results of routine investigations, including complete blood count, liver function test, kidney function test, and serum electrolyte levels, were found to be within normal limits. Nasal endoscopy revealed septal perforation; however, no biopsy was taken during endoscopy. To rule out syphilis, the serum sample was subjected to a nontreponemal (VDRL) and treponemal (T. pallidum hemagglutination assay [TPHA]) test. Initially, a qualitative VDRL test was performed, using VDRL antigen from the Institute of Serology, Kolkata, West Bengal, India, which was nonreactive. Owing to high clinical suspicion of syphilis, a quantitative VDRL test was performed to rule out the prozone phenomenon. The quantitative VDRL test was positive with the titer of R 64 dils., with the prozone phenomenon at lower dilution (nonreactive in undiluted serum) and reactive at higher dilutions (ranging from 1:2 to 1:64) [Table 1] and [Figure 1]. To confirm the results of the nontreponemal test, TPHA (IMMUTREP® TPHA, Omega Diagnostics Ltd., United Kingdom) test was performed on serum dilutions ranging from 1:80 to 1:5120 and was found to be negative for treponemal antibodies in each of the serum dilutions [Figure 2]. Based on the results of the VDRL and TPHA tests, it was concluded that the patient had a false positive reaction with the prozone phenomenon due to a condition other than syphilis. His laboratory workup for connective tissue disorders, which included rheumatoid factor, antinuclear antibody, cytoplasmic antineutrophil cytoplasmic antibodies, and perinuclear antineutrophil cytoplasmic antibodies, returned negative. He was negative for serological markers for HIV, HBV, and HCV infection (i.e., HIV-antibody, HBsAg, and HCV-antibody, respectively).
Table 1 Result of quantitative VDRL test

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Figure 1 Quantitative VDRL test showing prozone phenomenon at lower serum dilution (non-reactive in undiluted serum) and reactive at higher serum dilutions (ranging from 1:2 to 1:64) (100x)

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Figure 2 TPHA test negative for treponemal antibodies at serum dilutions ranging from 1:80 to 1:5120. (CC: Control cells; TC: Test cells; NC: Negative control; PC: Positive control)

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The patient was referred to the Medicine and Dermatology outpatient clinics for further evaluation. On eliciting the history, it was revealed that the patient was apparently well 3 years back when he started to develop numbness and a decrease in sensation involving both the lower limbs, which gradually progressed to involve the upper limbs. He reported slipping off his footwear while walking. He had a history of tingling sensation over both lower and upper limbs. He noticed gradually increasing swelling involving his face and both the ears over the past 1 year. He also noticed decreased sweating and dryness of skin. He denied using intravenous drugs. He denied having signs and symptoms suggestive of syphilis. He reported being in a monogamous relationship with only his wife who also denied having any signs and symptoms suggestive of syphilis. On general physical examination, the patient was found to have leonine facies with the widening of the nasal bridge and the loss of eyelashes (madarosis) [Figure 3]. Thickening of skin over the ears was also observed [Figure 4]. There was pitting edema on lower limbs and generalized dryness of skin. There was thickening of bilateral greater auricular nerves, ulnar nerves, and superficial peroneal nerves. There was a decreased perception of pain in bilateral lower and upper limbs in glove and stocking patterns. The nerve conduction velocity test showed distal symmetric predominately axonal sensory neuropathy. In view of high clinical suspicion of Hansen's disease, slit skin smears were prepared from various sites and were subjected to modified Ziehl-Neelsen staining. The stained smears revealed the presence of acid-fast bacilli with parallel sides and rounded ends, suggestive of Mycobacterium leprae. The acid-fast bacilli were also found to be arranged parallelly in clumps, known as globi [Figure 5]. The Bacteriological Index was calculated as 4+. Based on the clinical and laboratory findings, the patient was diagnosed as a case of lepromatous leprosy with distal symmetrical axonal sensory neuropathy. The patient was started on World Health Organisation recommended 12-month multidrug regimen for multibacillary leprosy, comprising rifampicin, dapsone, and clofazimine.
Figure 3 Photograph of the patient showing leonine facies with the widening of nasal bridge and madarosis.

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Figure 4 Photograph of the patient showing thickening of the skin over the right ear.

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Figure 5 Modified ZN staining of the slit skin smear made from the right ear lobe revealing acid-fast bacilli arranged in globi (1000x)

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  Discussion Top


The VDRL test for syphilis may under, a certain set of conditions, give false positive results in patients who are not infected with T. pallidum. A false positive reaction is defined as a positive reaction to nontreponemal tests, and a negative reaction to treponemal tests, in the serum of a patient who has no history or clinical evidence of syphilis or other treponematosis. The false positive reactions are categorized as acute or chronic. Acute false positive reactions usually develop during or shortly after an acute infection and last for a few days to a few weeks, or no more than 6 months after the patient’s recovery. Well-known causes of acute false positive reactions are pregnancy, infectious mononucleosis, measles, chickenpox, hepatitis, viral pneumonia, malaria, and immunizations.[1] Chronic false positive reactions are defined by the persistence of reactive nontreponemal tests for a period exceeding 6 months. Chronic false positive reactions are associated with connective tissue disorders (e.g., systemic lupus erythematosus), intravenous drug use, malignancy, older age, and leprosy.[1] The reactivity in such cases is usually seen in low dilutions (<1:8),[1] and is unlikely to show a prozone phenomenon. A prozone phenomenon in nontreponemal tests is seen largely with secondary syphilis due to high-titer samples that show nonreactive results unless the specimens are diluted.[2]

We describe here perhaps the first case of lepromatous leprosy that had a false positive reaction to the VDRL test with the prozone phenomenon. The presence of nontreponemal antibodies in this case can be attributed to the progressive tissue damage due to lepromatous leprosy, leading to the release of lipoidal material (mostly cardiolipin antigen) from the damaged host cells and the subsequent formation of antibodies to the cardiolipin antigen. Though on the literature search we could not find any report of false positive VDRL test with prozone phenomenon in a case of leprosy, there was one report of a patient with lymphosarcoma who had VDRL test reactive at 1:256 along with prozone phenomenon.[3]

The finding of septal perforation on nasal endoscopy is what led to the initial suspicion of syphilis and the subsequent syphilis workup. It was only when the false positive reaction to VDRL test with the prozone phenomenon was noted that the search for other causes was made, which eventually led to the diagnosis of lepromatous leprosy. Nasal septal perforation is also a known manifestation of leprosy,[4] which as one of the differential diagnoses was overlooked during the initial workup. This case illustrates the significance of close liaison between medical laboratory professionals and clinicians to achieve favorable patient outcomes.

[TAG:2]Declaration of patient consent[/TAG:2]

The authors certify that they have obtained informed consent from the patient. The patient has given his consent for the inclusion of his images and other clinical information in the journal. The patient understands that the name and initials will not be published and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Larsen SA, Steiner BM, Rudolph AH. Laboratory diagnosis and interpretation of tests for syphilis. Clin Microbiol Rev 1995;8:1–21.  Back to cited text no. 1
    
2.
Morshed MG, Singh AE. Recent trends in the serologic diagnosis of syphilis. Clin Vaccine Immunol 2015;22:137–47.  Back to cited text no. 2
    
3.
Wuepper KD, Tuffanelli DL. False positive reaction to VDRL test with prozone phenomena. Association of lymphosarcoma. JAMA 1966;195:868–9.  Back to cited text no. 3
    
4.
Shah AR, Zeitler D, Wise JB. Nasal reconstruction of the leprosy nose using costal cartilage. Otolaryngol Clin North Am 2009;42:547–55.  Back to cited text no. 4
    


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