By Carol A. Kemper, MD, FACP

Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center

Dr. Kemper reports no financial relationships relevant to this field of study.

Objects of Delusional Infestation

SOURCE: Garcia-Mingo A, Dawood N, Watson J, Chiodini PL. Samples from cases of delusional parasitosis as seen in the UK Parasitology Reference Laboratory (2014-2015). Open Forum Infect Dis 2019;6:ofz440.

I loved this article and the photos! What ID specialist has not seen his or her share of patients with delusional parasitosis? Patients often provide you with “proof” of their infestation, with the odd bits of debris, fabric, and even earthworms in baggies or boxes. With the advent of smartphones and tablets, we have even seen elaborate videos with “moving” bits of debris on skin. Delusional parasitosis takes many different forms, with delusions of skin infestations (ticks, mites, or parasites), enteric infections (with parasites and worms), or brain infections (small living organisms invading brain tissue). Some of the more recent Morgellons disease patients believe their flesh has been penetrated by diverse entities, such as parasites, Borrelia, or experimental fibers from the sky, like some radical science fiction plot.

Earlier studies found that samples submitted by patients were largely bits of skin, scabs, or textile fibers. Often, these materials are submitted to pathology. The authors at the UK Clinical Parasitology Laboratory performed a prospective survey of 138 samples provided by 123 patients with delusional parasitosis. Ten patients submitted multiple specimens. Most of the patients had been diagnosed with delusional parasitosis at the Hospital for Tropical Diseases, but several had been seen by primary care or dermatology. More than half (59%) of the samples were submitted by women. The average age of the patients was 48 years (range, 39-62 years). Specimens were submitted in matchboxes, plastic bags, Tupperware, and tinfoil. Two pathologists examined each sample, and specimens with suspected insects were submitted to an entomologist at the School of Tropical Medicine and Hygiene for further opinion.

Many of the samples contained mixed material. The most common findings, in descending order, were synthetic or textile fibers (18.1%), skin flakes or scabs (17%), hair (9.4%), insects (not ectoparasites) or nonpathogenic worms (9.4%), plant or vegetable matter (7.2%), mucus (4.3%), nails (1.4%), and dirt (< 1 %). Of the possible insects or parasites, five were earthworms, one was a leech, one was an annelid worm, one was insect larvae, and four were fragments of insects too small or disintegrated to identify. No human pathogenic parasites or ectoparasites were identified.

The pathologists concurred that microscopy is entirely appropriate for these cases, not only to provide evidence to the patients about their misconception, but because many items require microscopy for proper identification. To the naked eye, it may be difficult to differentiate mucous strings from parasites, or plant fibers from ectoparasites, or seeds from eggs. While pathologic examination is helpful feedback to the clinician, I have not seen it convince many of these patients.

Urine Eosinophils Unreliable

SOURCE: Strasma A, Kullcarni SA. Overuse of urine eosinophils in the diagnosis of acute interstitial nephritis. A teachable moment. JAMA Intern Med 2019;179;1131-1132.

The authors report a case of acute interstitial nephritis (AIN) in an elderly man receiving a seven-day course of levofloxacin, who developed frank renal failure with a serum creatinine of 6.7 mg/dL. Urine microscopy showed occasional white cells and no casts and there were no urine eosinophils. And yet, the nephrologist diagnosed AIN from oral levofloxacin use an important diagnosis for the future management of this patient. How could this be?

The bottom line, in contrast to common practice, is that urine eosinophils are not useful in the diagnosis and management of AIN, and inappropriate dependence on the presence of urine eosinophils may be dangerous, resulting in future exposure to a damaging drug. Interstitial nephritis is an immune-mediated condition that may result from exposure to many different drugs, but the most common offenders are penicillin drugs and fluoroquinolones. In the hospital setting, AIN may occur in up to 20% of patients, but it is under-recognized or misdiagnosed frequently as the result of other systemic causes. In cases of acute kidney injury with renal biopsy, AIN was present in 6% to 30% of cases. In cases of AIN without urine eosinophils, few eosinophils were present in the interstitial inflammatory infiltrate. In contrast, urine eosinophils have been described with other causes of acute renal injury, e.g., acute tubular necrosis.

In one larger study of 566 patients with biopsy-proven AIN, the sensitivity of urine eosinophils (> 1%) was only 30% and the specificity was 68%. The positive and negative likelihood ratios were 0.97 and 1.01, respectively, which suggests that urine eosinophils are not helpful in the diagnosis of AIN.

AIN from immune-mediated drug reactions may occur in conjunction with systemic symptoms, including dermatitis, peripheral eosinophilia, fever, and arthralgias but not always. Since AIN may occur in the absence of drug eruption and/or urine eosinophils, the clinician must make the diagnosis based on a heightened suspicion of a possible drug effect, and all suspect agents must be discontinued promptly.

Tecovirimat for Laboratory-Acquired Vaccinia

SOURCE: Whitehouse ER, Rao AK, Yu YC, et al. Novel treatment of a vaccinia virus infection from an occupational needlestick — San Diego, California, 2019. MMWR Morb Mortal Wkly Rep 2019;68:943-946.

While injecting mice, a laboratory worker acquired vaccinia virus infection through an accidental needlestick in her index finger. She had declined vaccination for smallpox, as recommended by the Advisory Committee on Immunization Practices for laboratory workers working with replication-competent vaccinia virus strains. The time line is fascinating: Between days 2 and 9, the worker remained asymptomatic and was seen by two different community physicians, who provided no infection control precautions or advice about the risk of infection transmission. On day 10 post-inoculation, she developed pain and swelling of the digit with a single vesicular lesion, and by day 12, she developed a low-grade fever and left axillary adenopathy, with worsening pain and swelling of the digit.

The Centers for Disease Control and the San Diego Public Health Department were contacted, and, on day 12, she was provided a single parenteral dose of Vaccinia Immune Globulin (VIGIV) and was started on tecovirimat 600 mg twice daily for two weeks. At day 13, the finger lesion began to suppurate. Within 48 hours of treatment initiation, she felt better, the fever and axillary adenopathy were improving, and the finger pain and swelling were diminishing. She continued to develop a necrotic lesion at the wound site on the finger, which did not heal for three months, and she was excluded from work. Antibody studies at day 25 showed demonstrable IgM and IgG antibody to orthopoxvirus, possibly from the VIGIV. Nonvariola orthopoxvirus DNA was amplified from the wound using real-time PCR, although the strain was not identified.

Remarkably, neither the patient nor the lab could identify the strain of orthopoxvirus involved. She had been injecting mice with different strains and could not recall when the needlestick occurred. Later, the company admitted that perhaps the Western Reserve strain of vaccinia virus was involved. The Western strain is considered the most virulent strain of vaccinia virus in animal models and is being used in bioengineering models for tumor selectivity through gene deletion.

Tecovirimat is a novel inhibitor of viral p37 and blocks the ability of virus particles to be released from infected cells. It is the only agent approved by the U.S. Food and Drug Administration for use against smallpox, and it is available through the federal investigational new drug protocol for use in select orthopoxvirus infection, such as this event. Currently, the United States maintains stockpiles of tecovirimat in case of a bioterrorism event. The patient seemed to respond quickly to the initiation of treatment, although the role of the antiviral vs. immunoglobulin therapy is not clear.

Laboratory workers engaged in research with replication-competent orthopoxvirus should receive appropriate vaccination. This patient was offered the vaccine but declined. She said later that this was because she did not understand the risks involved, and was concerned about potential vaccine side effects.