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A28-YEAR-OLD MAN with a history of HIV on bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) with undetectable viral load presented to the emergency department (ED) after being called by a nurse to return for abnormal syphilis test results. He was seen twice in the week prior to this visit, once at a local urgent care for a penile lesion with discharge around the glans and fever, and more recently in the ED for reduction of paraphimosis. Although the patient explained he had not received notice of any positive results from the urgent care, the specimens sent by the ED 3 days prior were positive for Treponema pallidum antibody (EIA) and positive for T. pallidum particle agglutination (TP-PA). Additional laboratory tests obtained during that visit included complete blood count (CBC), basic metabolic panel (BMP), urine analysis (UA), chlamydia (CT), gonorrhea (GC), and rapid plasma reagin (RPR). UA was abnormal but showed no bacteria (see Table 1). CBC and BMP were normal, and CT, GC, and RPR were negative. The patient was discharged from the ED after treatment with ceftriaxone and advised to continue the clotrimazole 1% and doxycycline prescribed 2 days earlier by urgent care for balanitis and urethritis.
Table 1. - Case patient's urinalysis test results Color Amber hazy Yellow clear Specific gravity 1.010 1.005–1.030 pH 7 5.5–7.5 Blood Negative Negative Protein 30+ Negative Nitrate Negative Negative Leukocyte esterase Negative Negative Bacteria None Non-few/hpf White blood cells 42 0–5/hpf Red blood cells 16 0–5/hpf Epithelial cells Many None-few/lpfNote. hpf = high powered field; lpf = low power field.
Upon arrival, the patient explained he was contacted by the nurse and needed to receive treatment for syphilis. He reported a rash, swollen penis, and persistent pelvic discomfort since being discharged. Over the last 3 days, a rash that he initially dismissed as insect bites to his bilateral lower legs had spread, involving all four extremities and his back and chest. Some of the lesions crusted and were healing, others were draining clear fluid, and all itched. There was no associated redness or swelling around the individual lesions. Nothing seemed to improve or worsen the rash. His penis remained swollen, but the penile pain was much improved since the paraphimosis reduction. Additionally, the penile lesion and penile discharge had resolved. The pelvic discomfort was associated with swelling to both sides of his groin. Review of symptoms was significant for fever, headache, fatigue, and myalgias, which had begun 5 days ago and were now resolved. He denied weight loss, chest pain, shortness of breath, eye pain or redness, change in vision, abdominal pain, dysuria, frequency, flank pain, and other swollen glands.
The patient's sexual history was significant for two male partners in the last 6 months without use of a barrier contraceptive. One sexual encounter was within a long-term committed relationship, whereas the other encounter was with a new partner approximately 2 weeks ago. He reported both partners had recently tested negative for syphilis, gonorrhea, and chlamydia, but he was uncertain whether they were tested for mpox. The patient smoked marijuana, was a former cigarette smoker, but denied other drug use.
On physical examination the patient was alert, appropriate, and appeared nontoxic. He had multiple papular and pustular flesh-colored, hyperpigmented, circumscribed 5-mm lesions to his back, chest, and all four extremities. The lesions were in various stages of healing with occasional crusts and a few lesions draining scant amounts of serous fluid (see Figures 1 and 2). No lesions were seen in the mouth, on the palms, or on the soles of feet. Bilateral inguinal lymph nodes were 1.0 cm to 2.0 cm and tender to palpation. His penis was edematous, and phimosis was noted. There was no urethral discharge or lesions present on his genitalia. Bilateral sclera was clear, no drainage from the eyes was present, and lungs were clear to auscultation. All other physical examination findings were unremarkable.
Figure 1.: Evolving lesions in mpox. Images of evolving lesions to extremities and a penile lesion with associated penile edema. From “Clinical Features and Novel Presentations of Human Monkeypox in a Central London Centre During the 2022 Outbreak: Descriptive Case Series” by A. Patel, J. Bilinska, J. C. H. Tam, D. Da Silva Fontoura, C. Y. Mason, A. Daunt ... A. Nori, 2022, BMJ, 378, e072410. doi:10.1136/bmj-2022-072410. https://creativecommons.org/licenses/by-nc/4.0 (nationalarchives.gov.uk).
Figure 2.: Images of pustular lesions to hands associated with mpox. Reproduced with permission from Juliet Aylward, MD, FAAD, FACMS, published by Medscape Drugs & Diseases (https://emedicine.medscape.com/), Monkeypox, 2022, available at: https://emedicine.medscape.com/article/1134714-overview.INTRODUCTION
Mpox is an emerging disease that challenges clinicians to hone their clinical diagnostic skills and remain vigilant. First diagnosed in 1970 in the Democratic Republic of the Congo as a zoonotic disease of young children, it is now disproportionately affecting men who have sex with men (MSM) across the globe (Bunge et al., 2022; Patel et al., 2022). It is spread by contact with skin lesions, respiratory droplets, oral fluids, and contaminated objects. The virus causes a variety of symptoms, most notably a pustular rash associated with fever, headache, fatigue, myalgias, and swollen lymph nodes (Walter & Malani, 2022). It can be mistaken for more common STIs and other viral illnesses due to the variability of severity and prevalence of symptoms. The lesions themselves evolve over time, ranging from only a few to thousands of pustules with the location depending on the site of inoculation, and a latent period extending up to 21 days makes contact tracing difficult (Guarner, del Rio, & Malani, 2022; Soheili et al., 2022). Limited testing availability, which is reserved for patients with a visible rash, and long testing result time (several days) compound the diagnostic challenges experienced in this outbreak (Centers for Disease Control and Prevention [CDC], 2022b). Consequently, emergency nurse practitioners (ENPs) must remain informed regarding the disease's epidemiology, risk factors, and diagnostic criteria to provide appropriate care and anticipatory guidance often in the absence of conclusive results. This article discusses the clinical features unique to mpox to prepare ENPs to face this public health emergency with increased awareness.
PATHOGENESISMpox is in the Poxviridae family and the Orthopoxvirus genus, which includes the variola virus that causes smallpox, a disease that shares similar pathophysiology and clinical manifestations without the viral host range. Mpox is unique because it is zoonotic, capable of infecting both animals and humans, and being spread between them (Haller, Peng, McFadden, & Rothenburg, 2014; Soheili et al., 2022; Yu, Bruneau, Brennan, & Rothenburg, 2021). Transmission occurs through close contact with infected animals or humans via contact with body fluids, feces, lesions, respiratory droplets, or contaminated items. It lives, grows, and multiplies within common rodents, nonhuman primates, and humans. While endemic in west and central Africa for decades, this most recent outbreak of human mpox has included over one hundred different countries and territories (Soheili et al., 2022).
Mpox is a complex DNA virus composed of over 200 DNA sequences transcribed at various stages of infection and designed to replicate entirely within the host cytoplasm upon entry of a single virion (Haller et al., 2014; Moss, 2013; Oliveira, Rodrigues, Lima, Drumond, & Abrahão, 2017; Walsh, 2017). Immediate transcription begins with virion core entry into the cell, along with viral enzymes and transcription factors, allowing for early gene expression that creates a protein for DNA replication. This template allows for further replication and transcription within the cell. Viral gene expression drives the remodeling of the endoplasmic reticulum to create viral proteins. Some of these virions will develop an additional outer membrane, becoming wrapped virions equipped to leave the cell via exocytosis. Entry of the enveloped virus is facilitated by interactions of negatively charged polysaccharide compounds and glycoproteins on the cell surface (Soheili et al., 2022; Walsh, 2017).
Early viral gene expression generates a state of unresponsiveness in T cells, thereby countering immune surveillance (Hammarlund et al., 2008). Viral immunomodulatory proteins inhibit the innate immune system's ability to detect pathogen-associated molecular patterns, thereby preventing the initiation of an adaptive immune response. These immunomodulatory proteins also interact with key components of intracellular signaling pathways, inhibiting apoptosis, natural killer cells, chemokines, inflammatory cytokines, complement proteins, and immunoglobulins (Soheili et al., 2022; Yu et al., 2021).
CLINICAL MANIFESTATIONSMpox is largely indistinguishable from other pox viruses, and easily mistaken for numerous other diseases and STIs (see Figures 3–5). Similar to syphilis, mpox predominantly impacts disparate populations, with the most recent surge disproportionally affecting MSM and associated with HIV infection. The primary lesions of both diseases often go unnoticed, and when located on the genitals, the open lesions increase the spread of other STIs by direct contact with infected skin (Hook, 2017; Soheili et al., 2022). Additionally, the wide range of mpox clinical symptoms can imitate many other diseases (CDC, 2022b; Soheili et al, 2022). The most recent surge in cases presenting with novel symptomology including solitary lesions, penile edema resulting in both paraphimosis and phimosis, oropharyngeal lesions, secondary bacterial infections with purulent penile discharge, rectal perforation, and abscesses (Patel et al., 2022). These new clinical presentations further impair clinicians' ability to recognize mpox and may be atypical and more severe in the setting of immune suppression and HIV coinfection requiring enhanced awareness and caution to intervene early and prevent the onward transmission (CDC, 2022a; Patel et al., 2022).
Figure 3.: Lesions associated with syphilis. CDC/Sumpter, R. (1967). Photograph of anterior view of a patient's upper torso, who had presented with a macular papulosquamous outbreak of syphilids; ID#12578. From Centers for Disease Control and Prevention Public Health Image Library (PHIL) (Retrieved January 13, 2023, from https://phil.cdc.gov/Details.aspx?pid=12578). In the public domain.
Figure 4.: Lymphadenopathy associated with syphilis. CDC/Lindsley, S. (1977). This image depicts an anterior view of a patient's groin, who had presented with phimosis, as well as swollen lymph nodes, known as lymphadenopathy, which was determined to be due to a case of primary syphilis. One of the symptoms of primary syphilis is the presence of swollen inguinal lymph nodes, either bilaterally or unilaterally, as well as the presence of a primary chancre; ID#3479. From Centers for Disease Control and Prevention Public Health Image Library (PHIL) (Retrieved January 13, 2023, from cdc.gov). In the public domain.
Figure 5.: Rash of secondary syphilis. CDC/Lindsley, S. (1977). This photograph depicts an anterior view of a male patient's lower torso, and thighs, including the knees, revealing the presence of a pustulo-papular rash, which was determined to be a case of secondary syphilis, caused by the bacterial spirochete, Treponema pallidum; ID#17885. From Centers for Disease Control and Prevention Public Health Image Library (PHIL) (Retrieved January 13, 2023, from https://phil.cdc.gov/Details.aspx?pid=17885). In the public domain.Mpox has an incubation period that ranges from a few days to up to 3 weeks post-exposure and is considered transmissible from the time of symptom onset. Skin lesions are the most common, yet varied feature of the disease, appearing a few days after prodromal symptoms of fever, chills, lymphadenopathy, headache, and myalgias (Soheili et al., 2022). The lesions progress through several stages presenting initially as macules and papules, then pustules, vesicles, and finally crusts anywhere on the body including the face, mucous membranes, palms, soles of the feet, and genitals (CDC, 2022b; Soheili et al., 2022). The rash is similar to the cutaneous findings noted in smallpox and secondary syphilis; it is typically pruritic but can be painful or painless and lasts between 2 and 4 weeks with complications related to secondary bacterial infections causing keratitis, pulmonary distress, pneumonia, and encephalitis (Ahmed, Naseer, Arshad, & Ahmad, 2022; CDC, 2022b; Hook, 2017; Soheili et al., 2022). These noncutaneous manifestations are also similar to those associated with smallpox and secondary syphilis, which are both associated with a wide range of noncutaneous manifestations. Other common symptoms of mpox include sore throat, cough, abdominal pain, vomiting, diarrhea, constipation, conjunctivitis, and in rare instances confusion, all of which can be seen in a variety of other viral illnesses.
MANAGEMENTManagement revolves around minimizing risk for secondary bacterial infection and preventing the spread of mpox to close contacts including health care workers, sexual partners, and household members. Isolation is recommended until all lesions are resolving and can be covered, although some individuals shed virus by respiratory droplets even after the rash is improved (Adler et al., 2022; County of Los Angeles Public Health, 2022). Although there are no specific therapies available for mpox, there is a role for vaccination, antivirals, and immunoglobulins to support patient recovery.
To date, second- and third-generation smallpox vaccines are recommended both for prevention of disease and within days after exposure to prevent severe symptoms (see Table 2; Patel et al., 2022; Soheili et al., 2022). Jynneos (Bavarian Nordic A/S), a third-generation vaccine, is safe for patients with HIV and has not been associated with risk in pregnancy or breastfeeding. It is administered as two doses timed 4 weeks apart with evidence of immunity 2 weeks later; however, no established immune correlates of protection are available (CDC, 2022c,2022d). Several antiviral medications including tecovirimat, cidofovir, and brincidofovir, a prodrug of cidofovir, are available as treatment options, but data regarding their level of effectiveness are limited (see Table 3; CDC, 2022a; Sherwat, Brooks, Birnkrant, & Kim, 2022; Soheili et al., 2022). Tecovirimat is the treatment of choice due to its safety profile and availability both as an oral capsule and in an intravenous solution. It works by inhibiting the viral envelope protein that is necessary to leave the infected cell and spread within the host. Vaccinia immune globulin can also be considered in those exposed with severe immunodeficiency; however, the mechanism of action and effectiveness in humans remains unclear (CDC, 2022a; Soheili et al., 2022).
Drug Brand names Classification Considerations Side effects Administration Immunity MVA vaccine (Bavarian Nordic A/S) Jynneos Imvamune Imvanez Third generation Safe for patients with HIV, skin conditions, no associated risk with pregnancy or breast feeding Injection site reactionsAfter physical examination, the ENP contacted epidemiology and infectious disease (EID) per hospital protocol to report the suspected mpox case to the public health department and arrange for Orthopoxvirus PCR testing. Two samples were collected for mpox testing by vigorously brushing the base of two different lesions from two different areas on the patient's body using a dry swab, which were placed into virus transport media and sent to laboratory. The patient was placed in isolation for possible mpox, and treatment of early reinfection of syphilis was administered because of his positive EIA and TP-PA results. He was ultimately discharged from the ED after discussing the risk for secondary bacterial infections with instructions for isolation and primary care follow-up. Strict return instructions were provided regarding fever, chills, headache, confusion, cough, shortness of breath, weight loss, worsening lymphadenopathy, pain, worsening penile swelling or paraphimosis, inability to urinate, redness or streaking around localized skin lesions, and any other new or worsening symptoms. The patient was advised to notify sexual partners, abstain from intercourse, avoid close contact and sharing of personal affects with others, and keep all lesions covered until mpox test results became available.
EID reported the suspected case and treponemal test results to the county health care agency later that afternoon and were informed the patient had indeed been tested for mpox 5 days prior and those results returned positive. The patient was informed by phone, contact tracing efforts were initiated by the county, and he was placed on isolation until no new lesions appeared and existing lesions could be covered or were completely resolved. Normal activities involving direct physical contact could be resumed after complete resolution of all lesions and associated symptoms (County of Los Angeles Public Health, 2022). Given that symptom onset was 7 days prior and he was improving, no additional medical interventions were indicated. The patient was advised to follow up with his primary care provider as discussed at discharge, with expected full resolution of symptoms. All ED staff that had been involved with his case were alerted to their exposure and asked to monitor for symptoms.
Unfortunately, the patient had several novel and atypical symptoms that prevented him from being identified as needing isolation precautions by the initial triage process. Additionally, the patient was under the impression that all initial testing completed at the urgent care clinic was negative, thus lowering suspicion. In retrospect, although the delay in final diagnosis may have been unavoidable given the prolonged laboratory turnaround time, had mpox been considered earlier in the patient's disease course he may have benefited from approved therapies and exposure to the public and health care workers could have been mitigated. The ENP conducted a follow-up phone call 1 week later and verified that all symptoms were resolved. The patient did not return to the ED and required no further treatment for mpox infection.
CONCLUSIONThe current surge in mpox cases has illuminated existing disparities and barriers to medical care, which include a lack of awareness and knowledge about the disease. This case illustrates the need for those on the frontline to remain vigilant to assessing for mpox and highlights the challenges this reemerging disease presents for the patient, clinician, and greater health care team. Mpox can be easily confused with more common dermatological conditions, viral illness, and STIs, which requires clinicians to maintain a high level of suspicion. The diagnosis of mpox should be considered for all patients presenting with a history of high-risk sexual activity including but not limited to MSM, sex workers, individuals with multiple partners, or history of HIV (CDC, 2022a,2022d; Guarner et al., 2022). Ensuring access to diagnostic testing, treatment, and supportive care is vital to contain the spread of this infectious disease. Early recognition is key to improve patient outcomes and limit the spread to sexual partners, household members, and health care workers. ENPs play an essential role in this public health emergency and must be prepared to identify and manage these patients.
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