Nausea, Vomiting, and Nonbloody Diarrhea in the Emergency Department

Abstract

Nausea, vomiting and diarrhea are frequent co-occurring symptoms that can mask or mimic commonly occurring conditions, or rarely, more serious concerns. The Ending the HIV Epidemic’s focus on increased widespread use of PrEP, a biomedical HIV prevention strategy, highlights the importance of discussing common clinical management scenarios. The use of oral PrEP formulations has demonstrated a “startup syndrome” which involves GI upset. This case challenge of a 32year old client admitted to the ED with GI symptoms highlights key PrEP considerations including a sexual health history. Clinicians should understand common complaints associated with oral PrEP start to improve differential diagnosis and appropriate intervention.

Introduction

A 32-year-old individual who was previously healthy has presented to the emergency room with persistent (4 days) nausea, vomiting, non-bloody diarrhea. The nurse practitioner (NP) must possess proficiency in both the physical assessment of the patient and subsequent diagnosis, while providing culturally competent care. Also essential is the NP’s ability obtain a thorough health history, conduct appropriate and timely physical exam and order and interpret relevant laboratory and radiological tests.

Case Presentation

A 32-year-old male customer service representative presented to the emergency room with complaints of 4 days of nausea, vomiting and diarrhea. The patient had a past medical history that included well-controlled asthma. The only current medications were emtricitabine (F) 200 mg and tenofovir disoproxil fumarate (TDF) 300 mg (F/TDF or Truvada), and Albuterol inhaler PRN. All immunizations were up to date, the patient was a nonsmoker, and denied any recent international travel. They did recall recently attending a community music festival 2 weeks prior with a group of close friends. The physical examination was unremarkable. Oral temperature was 36.7°C (98.06°F), blood pressure was 123/78 mmHg and the pulse was regular and 108 beats per minute. Lungs were clear on auscultation, no wheezing. Abdominal exam is benign. Skin was without rash, no palpable lymph nodes, and oropharynx was pink and moist.

Case Challenge Questions

1. What additional information, from the patient, will aid in the clinical management?

2. What studies should be considered and/or ordered to aid the diagnosis?

3. What diagnostic studies should be considered and/or ordered?

4. What are the best management strategies for this patient?

Case Challenge Questions with Answers

1. What additional information, from the patient, will aid in the clinical management?

While not immediately apparent based upon the presentation symptoms, a thorough sexual health history is essential given the context of the presentation and lack of physical exam findings. PrEP (preexposure prophylaxis), an antiretroviral medication, is prescribed to prevent HIV through sex or injection drug use in adolescents and adults¹. The use of PrEP indicates that through shared decision making, this patient and their provider established the benefit of PrEP in preventing HIV. Investigating why the patient is taking this medication and for how long will help the NP establish the necessity for a sexual health history. Once established that F/TDF is being taken as PrEP for sexual prevention of HIV, a thorough sexual health history can assist in developing our differential, drive our diagnostics and provide an opportunity to educate the patient. When approaching a sexual health history, it is best to apply the “6Ps” approach. Adapted from the CDC’s “5 Ps” approach, this simple pneumonic allows the NP to address all domains of a sexual and reproductive health history².

The Six “Ps”²

• Partners

• Practices

• Protection from STIs

• Past History of STIs

• Pregnancy Intention

• Pleasure & Performance

Often, sexual health histories can be uncomfortable for both NP and patient, so it is important to create a safe and welcoming environment in which to complete the sexual health history. Ask permission when navigating sensitive conversations and respond accordingly, provide privacy, establish pronouns, as well as their gender identity and sexual orientation. Training in trauma-informed care can assist the NP in applying a patient centered approach throughout the interaction. Understanding that the care we provide, especially care like sensitive exams (e.g., chest/breast, pelvic, or genital exams), can retraumatize patients is the first step in a trauma-informed approach. The traumatic events patients experience can be stored as physiological responses to a provider’s line of questioning for history collection, attempts to comfort the patient through cues like ‘relax’ or through physical exams. Acknowledging the power dynamic, minimizing stress, and maximizing autonomy are just a few ways to integrate this approach into clinical work³. Partners: It is essential that the NP understand the most recent sexual partners, their genders, and any additional risk factors of the partners (e.g., other concurrent partners, drug use or recent similar symptoms). It is important to not assume the sexual orientation or gender identity of the patient or their partners. Practices: Asking about the patients’ sexual practices will guide the NP to determine necessary testing, designate the anatomical site(s) from which to collect specimens, expand on the physical exam or guide risk-reduction discussions. Protection from STIs: Inquiring into prevention methods (e.g., condoms, biomedical prevention) allows the NP to appropriately counsel the patient on risk reduction strategies. Past History of STIs: A patient with a previous history of STIs may possess greater risk for a STI at presentation. To collect this history, you may simply ask if the patient has ever, in their lifetime, been diagnosed with a STI and give them specific examples (e.g., syphilis, chlamydia or gonorrhea). Additionally important is an investigation into the current possibility of having a STI. You can simply inquire if they know if recent partners have tested positive or have shared concern about symptoms consistent with a STI (e.g., dysuria or discharge). Pregnancy Intention: not always applicable but important for patients with the capacity for pregnancy to guide counseling. Pleasure and Performance: Understanding issues with sexual pleasure and performance may highlight areas for intervention (e.g., dyspareunia, erectile dysfunction, or medication side effects) which may benefit from specialist referral (e.g., physical therapy, urology, or gynecology).

When navigating the sexual health history with the patient, they disclose that they are nonbinary and use they/them pronouns. Additionally, they disclose they “were in a bit of a dry spell” prior to meeting their most recent sexual partner, so had previously stopped their PrEP prescription. Their motivation for restarting their PrEP prescription was a new sexual partner that they had met at the community music festival. This new partner identifies as male and is sexually active with both male and female partners. This new partner has a recent (6-month) history of 2 new male partners and his typical sexual positioning practice is “topping” or insertive anal intercourse. Our patient details that, with this partner, they performed and received oral sex and “bottomed” or receptive anal intercourse. Our patient is not aware of any personal past history of STIs and their most recent partner shared they had “tested” 3 months prior to their sexual activity but was unclear on details or results.

5. What are the differential diagnoses for this patient?

A diagnostic steward’s best tool is a thorough history. The patient presents with the complaint of nausea/vomiting/diarrhea the physical exam was unremarkable. To develop the necessary list of diagnostics and approach the final diagnosis we can categorize the differentials into each complaint and exam finding.

Acute nausea/vomiting/diarrhea –

typical causes of acute nausea/vomiting/diarrhea are infectious (e.g., viral, bacterial, or parasitic), medication side effects (e.g., chemotherapy), post-operative or CNS (e.g., migraine)⁴. The timing of onset is important as infectious causes typically occur hours to days after exposure or consumption⁴. Our patient denies any household members with similar symptoms, has not consumed any unpasteurized meats or dairy, raw meat, eggs or shellfish, no recent swimming in treated or untreated water, no recent antibiotic administration and does not work in food service, child or health care settings⁵. Most episodes of acute nausea/vomiting/diarrhea or gastroenteritis in immunocompetent hosts, who were previously healthy are viral or unknown in etiology and self-limiting⁵. In patients who are sexually active and who endorse anal intercourse or analingis (oral sex to the perianal area) it is important to consider fecal-oral route infectious diseases. Infectious enteritis usually causes diarrhea and abdominal discomfort without proctitis. These infections are often consequences of outbreaks within social or sexual networks, so the NP should inquire if any sexual partners or other close friends and family have similar symptoms. The most implicated pathogens are Giardia lamblia, Shigella species, Salmonella, Escheria coli, Campylobacter species and Cryptosporidium. Most concerning in men that have sex with men (MSM) are outbreaks of Shigella species given recent concerning antimicrobial resistance patterns⁶.

It is important to review with the patient, current and correct use of all medications. Upon further clarification of the clinical history, patient reports a restart of PrEP (F/TDF or Truvada) just prior to attendance at the music festival stating, “just in case I met someone interesting”. The use of the drug combinations F/TDF and F/TAF for oral PrEP have demonstrated a “startup syndrome” which involves nausea, vomiting and dirrhea⁷. This syndrome, noted in (<10%) patients on PrEP is often self-limiting and occurs within the first 2–4 weeks of initiating the medication¹. This syndrome can impact PrEP adherence, so patients need to be counseled on the possibility of medication side effects and strategies to manage them. This syndrome can be supported by OTC or prescription anti-emetics to assist the patient in tolerating PrEP or transitioning to other available PrEP medication formulations. Behavioral modifications, (e.g., taking PrEP with meals) can assist in reducing the risk of this “startup syndrome” as well.

2. What studies should be considered and/or ordered to aid the diagnosis?

Our history, physical exam and differentials have now laid the foundation for the next step of clinical management, which is ordering appropriate diagnostics. Diagnostic stewardship can increase efficiency, improve patient satisfaction and reduce unnecessary health care spending⁸. Patients on oral PrEP should have quarterly visits (every 3 months) with their provider for appropriate testing. Our patient’s last PrEP appointment was 6 months ago given scheduling conflicts. First, patients with a history of PrEP use, behavior that increases the likelihood of HIV infection (i.e., unprotected receptive anal intercourse) and nonspecific complaints it is important to screen with a laboratory-based antigen antibody HIV test to rule out HIV infection. Next, given the duration of vomiting and diarrhea there is potential for dehydration so checking a comprehensive metabolic panel and complete blood count would be another high priority. In addition, urine for urine analysis as well as for gonorrhea (GC) and chlamydia (CT) nucleic acid amplification tests (NAAT), throat swab for GC and CT NAAT and serum syphilis testing with a treponemal and nontreponemal test. For patients with or who engage in sex with a vagina consider trichomonas testing. Rectal swabs for GC and CT NAAT would aid in ruling out rectal infections and given recent sexual exposure would be indicated. Note that all anatomical sites of sexual contact are screened, this is due to the asymptomatic nature of infection in the oropharynx and rectum. If the NP has a large index of suspicion for other infectious causes of diarrhea (e.g., Shigella species) a stool specimen can be sent for culture. Additional considerations for patients with the capacity for pregnancy are pregnancy testing to rule out this concern.

6. What are the best management strategies for this patient?

Management of this patient would include oral rehydration solutions and/or intravenous fluid replacement with crystalloids depending on the severity of dehydration. In addition, this patient’s recent new sexual partner raises the question of empiric treatment for presumed STIs. Empiric STI treatment includes an (1) intramuscular injection of ceftriaxone 500 mg once plus (2) oral doxycycline 100 mg every 12 hours for 7 days. For persons who are 150 kilograms or greater, the intramuscular injection of ceftriaxone should be 1 gram. In the absence of symptoms or known STI positive sexual partners no empiric therapy would be indicated. The current CDC STI and PrEP guidelines contain contemporary evidence-based recommendations on the care and treatment, not only of PrEP/PEP and the associated start-up syndrome but also of STI screening, diagnosis, and treatment guidelines^1,9.

Conclusion

Common emergency department presentations such as nausea, vomiting and diarrhea can often mask or mimic commonly occurring conditions. The history of recent sexual activity prompted the patient to reinitiate their PrEP prescription. PrEP prescription stops and starts are common as individuals pass through “seasons of risk.” It is important the NP validate the patient’s decision to restart PrEP as another layer of protection against HIV infection. This medication restart however, caused a “startup syndrome” which is self-limiting and can be managed with OTC or prescription antiemetics and oral rehydration solutions can be encouraged. If the patient is hesitant to continue with their current PrEP formulation the NP should discuss management options through shared-decision making which include offering an alternative PrEP formulation (F/TAF or CAB-LA), optimizing symptoms through prescription and OTC medications, counseling on optimized medication administration behaviors or stopping PrEP and reengaging in care with the PrEP specialist. If the patient chooses to stop PrEP, the NP should advise them to utilize alternative barrier methods to prevent HIV (e.g., condoms). If the patient were to decide to continue their PrEP prescription as is the NP should counsel them on the time to efficacy. For patients who engage in receptive vaginal intercourse we have data to suggest effective levels at around 21 days after initiating the prescription. Individuals that engage in receptive anal intercourse or “bottoming” we have data to suggest effective drug levels 7 days after initiating the prescription. For individuals engaging in insertive anal or vaginal sex we do not have sufficient evidence to suggest time to efficacy. Additionally, in gay, bisexual and other men that have sex with men whose risk is receptive anal intercourse there is an alternative dosing strategy termed “on demand” or “2-1-1.” This is the administration of 2 pills (F/TDF) 2–24 hours prior to a sexual encounter and then 1 pill at 24 hours after the initial dose and 1 pill at 48 hours after the initial dose¹. This strategy assumes no additional sexual exposures within 24 hours of the final dose. If sexual exposure continues the individual can continue daily dosing as indicated for all populations. This dosing strategy is currently endorsed by The International AIDS Society of the US (IAS-USA), World Health Organization (WHO), and European AIDS Clinical Society (EACS) but is not FDA approved or recommended by the CDC¹. Unique to this administration strategy is the risk for amplified gastrointestinal symptoms (given the initial double dose), so the NP should discuss the risk and benefit of this strategy especially in patients who have demonstrated a “startup syndrome” with PrEP previously. All visits addressing PrEP should include a thorough sexual health history to establish necessary STI testing strategies. Most importantly, the NP should know and consider all potential sexually transmitted infections, their associated constellations of symptoms, and how to test and treat in a timely manner. Sexually transmitted infections are on the rise globally and across all populations. It is essential that NPs in all clinical settings familiarize themselves with the “6 Ps” approach to collect a comprehensive, trauma-informed sexual health history.

Figure 1.

PrEP FAQ

Highlights.

• Biomedical HIV prevention is essential to addressing the HIV epidemic.

• Oral preexposure prophylaxis (PrEP) has potential side effects collectively identified as a “start-up syndrome”.

• Clinicians not familiar with PrEP may mistake the “start-up syndrome” as other more common causes.

• Sexual health history collection is essential to fully develop disease differentials in sexually active populations.