Michelle Teasdale, DNP, APRN, FNP-C

Background

A 28-year-old male with a history of HIV presented to jail. During the prescreening process, he denied any symptoms of an acute illness or mental health condition and was booked into jail. A comprehensive nursing exam (CNE) was completed and notable for the following:

He was diagnosed with HIV in 2001 and has Bictegravir 50mg/emtricitabine 200mg/tenofovir 25mg once daily (Biktarvy) prescribed. The last dose was taken two weeks prior to presentation. He has no known allergies and no recent travel outside of the United States.

The patient has a 10-pack-years tobacco history. He drinks alcohol socially and has no history of illicit drug use. He has multiple male sexual partners, and his last sexual activity was one month prior to presentation. 

Physical Exam

Temperature, 98° F, Heart rate, 98 beats per minute, Blood pressure, 128/78 mm Hg, Respiratory rate, 16 breaths per minute, Oxygen saturation, 100% while breathing ambient air. He is well-appearing, well-nourished, alert and oriented, and in no acute distress. The review of systems (ROS) are negative per his report. All body systems during the head-to-toe examination are within normal limits. 

CNE Follow Up

An active Biktarvy prescription could not be verified. He was scheduled to follow up in the HIV clinic.

HIV Clinic Visit

The patient was evaluated in the HIV clinic two weeks after being booked into jail. He reported feeling well, without specific medical concerns. He tolerates Biktarvy without side effects. He denies fever, chills, or cough. The remainder of the ROS are negative, and all body systems are within normal limits.

The provider ordered a CD4/CD8 absolute and %, T-Cell Panel, an HIV viral load, and confirmation of prior Biktarvy prescription before starting.

Clinical Course

Biktarvy was initiated after evaluation in the HIV clinic. Eight days later, the patient discontinued Biktarvy due to a new rash. He was scheduled for a follow-up provider visit.

Provider Visit

Chief Complaint

Rash

Subjective

The patient reported five days of a new onset rash involving the entire torso and upper extremities. No fever, chills, or difficulty swallowing. He otherwise feels well.

Objective

Dermatologic exam – Vesicular rash covering the trunk, upper, and lower extremities with sparing of the palms and soles. There was no evidence of mucosal or ocular involvement.

Lab Results

CD4 count 100 cells/µL

HIV RNA Quant 861,000 copies/mL

The provider sent him to the hospital. Do you know why?

Answer: the provider’s impression was disseminated zoster following immune reconstitution inflammatory syndrome in a patient with HIV and a CD4 count of 100. He found this quite concerning due to the possibility of secondary sequelae, including eye involvement and encephalitis. 

What is Immune Reconstitution Inflammatory Syndrome?

Immune Reconstitution Inflammatory Syndrome (IRIS) depicts a group of inflammatory disorders associated with worsening preexisting infectious processes following the initiation of antiretroviral therapy (ART) in patients infected with HIV. Preexisting infections in individuals with IRIS may have been previously identified and treated or could be subclinical and unmasked by the individual’s regained capacity to produce an inflammatory response. If immune function improves rapidly with ART initiation, systemic or local inflammatory reactions may occur at the site of underlying the infection (Wolfe, 2019).

Patient Risk Factors

• Studies have demonstrated that lower CD4 cell counts or high HIV viral load at the time of ART initiation increase the risk of developing IRIS. The patient’s lab results revealed both.

The ER visit

Physical exam

All body systems are within normal limits with the following exception.

Skin – warm and dry. Notable lesions to arms, chest, back, small erythematous raised papular lesions. Some are scabbed and in various stages of healing.

Differential Diagnoses considered by the ER physician included chickenpox, mpox (formerly known as monkeypox), adverse reaction to Biktarvy, and syphilis.

The physician collaborated with an infectious disease specialist and an epidemiologist. It was determined that it was unlikely that Biktarvy caused the rash, and the medication should be continued. Testing for mpox, varicella, and syphilis was obtained.

Mpox

Mpox is a zoonotic viral infection. Most cases have been identified in men who have sex with men. Close contact with an infected skin lesion during sexual contact is the most likely mode of transmission. Person-to-person transmission can also occur through large respiratory droplets. The incubation period is 7-10 days after exposure (Isaacs & Mitja, 2022).

Mpox has traditionally caused a systemic illness during the prodromal or early clinical stage, including fevers, chills, and myalgias. A characteristic rash develops helping, to differentiate it from other vesicular rashes. The rash materializes one to two days before or three to four days after the onset of the systemic symptoms and persists for two to three weeks (Isaacs & Mitja, 2022).

The rash associated with mpox usually begins as 2 to 5mm diameter macules that simultaneously develop on any part of the body. The lesions evolve into papules, vesicles, and then pseudo-pustules. The lesions are well-circumscribed, deep-seated, and often develop umbilication. One to two weeks after the onset of the rash, the lesions crust over, dry, and fall off. The rash is usually described as painful but can be pruritic during the healing phase (Isaacs & Mitja, 2022).

Changes during the Mpox 2022 outbreak

During the 2022 mpox outbreak, some patients presented with a rash but did not have systemic symptoms, and not all lesions were in the same stage of development (Isaacs & Mitja, 2022).

Patient Risk Factors

• The patient reported he has multiple male sexual partners. 
• Vesicular rash in varying stages of development.

Varicella-zoster

Varicella-zoster virus (VZV) causes two recognizable diseases – chickenpox and shingles. Varicella is the primary infection and is known as chickenpox. The rash caused by chickenpox can occur anywhere on the body but is usually concentrated on the face and trunk. Vesicular lesions characterize the rash. The lesions are on an erythematous base and appear in different stages of development (Albrecht & Levin, 2022). 

During varicella, the virus establishes latency in the sensory ganglia and can become reactivated, resulting in herpes zoster, better known as shingles. The shingles rash occurs unilaterally in a single or two bordering dermatomes. The lesions are vesicular and painful. Systemic symptoms, such as fever, fatigue, or malaise, occur in less than twenty percent of patients (Albrecht & Levin, 2022).

Immunocompromised persons are at higher risk than the general population for VZV reactivation and the development of herpes zoster. The rate of complications, including herpes zoster keratitis, herpes zoster ophthalmicus, and encephalitis, are also significantly higher in immunosuppressed patients (Albrecht & Levin, 2022).

Patient Risk Factors

• Immunocompromised
• Biktarvy reinitiated, putting him at risk for IRIS/VZV virus vasculopathy. 
• Vesicular rash in varying stages of development.

Syphilis

Syphilis is transmitted from person to person by direct contact with a sore, known as a chancre. Chancres are lesions that can occur inside or on the penis, vagina, anus, rectum, lips, or mouth and can be transferred during vaginal, anal, or oral sex (Hicks & Clement, 2022).

Primary syphilis: the initial sign of infection is a chancre that can appear 21 days after exposure at the inoculation site. Typically, it appears on the genitals but may develop at other sites, including the posterior pharynx, anus, or vagina (Hicks & Clement,2022). 

The lesion begins as a papule and advances to an ulcer. The 1 to 2cm ulcer has a raised, indurated margin and is painless. Since the sore is painless and may go unnoticed, many patients do not seek medical attention, increasing the risk of transmission. The chancre usually heals within three to six weeks, even without treatment. Primary syphilis can quickly become systemic and is the cause of secondary syphilis (Hicks & Clement, 2022). 

Secondary syphilis: Twenty-five percent of people, mainly patients who have not been treated, develop systemic illness representing secondary syphilis. This can occur within a few weeks to a few months after the development of the chancre (Hicks & Clement, 2022). 

Secondary syphilis may produce various signs and symptoms, such as fever, malaise, sore throat, myalgias, and weight loss. The most characteristic finding is a diffuse rash that can present in any form, although vesicular lesions are uncommon. The rash involves the trunk, extremities, palms, and soles. Involvement of the palms and soles is a crucial finding in diagnosing secondary syphilis; however, localized lesions may also occur. Secondary syphilis symptoms may resolve spontaneously without treatment. (Hicks & Clement, 2022). 

Patient Risk Factors

• Patients with HIV are at higher risk for STIs.
• Immunocompromised 
• Rash

The Diagnosis – with lab results from the ER

Secondary Syphilis

He did not have any memory of a chancre and therefore did not know he had been infected. Although his rash was not characteristic of secondary syphilis, documentation shows that different presentations can be expected. 

Outcome

The recovery of immunological function resulted in unmasking the unknown preexisting syphilis infection. He received the first Bicillin 2.4 million unit injection before he left the hospital. Two more doses were prescribed one week apart. Since ART can predispose patients with IRIS to opportunistic infections, he was also prescribed Bactrim prophylaxis for pneumocystis jirovecii pneumonia.

When he returned to jail, he was placed in isolation until the other test results were available. The results for varicella and mpox were negative. He completed treatment for syphilis and continued on Biktarvy without complications. He was released from jail before follow-up HIV labs could be obtained.