Acute HIV presenting as rhabdomyolysis

Abstract

A man, in his early 30s, with no significant medical history presented with a 2-week history of fatigue, chest and abdominal pain, associated with anorexia and vomiting. Initial laboratory testing was suggestive of rhabdomyolysis with acute renal failure and transaminitis. The aetiology of his rhabdomyolysis initially remained unexplained as there were no clear risk factors or inciting events. An extensive workup revealed acute HIV as the precipitant of rhabdomyolysis.

Background

Rhabdomyolysis is an unusual manifestation of acute HIV infection. Clinical presentation with non-cardiac creatine kinase (CK) elevation >1000 IU/L can range from an asymptomatic, incidental finding, to a life-threatening disease causing severe acute kidney injury (AKI), major electrolyte disturbances and death in some cases.¹ Taking into account this unusual presentation, a diagnosis of primary HIV infection should be considered in patients found to have non-traumatic, non-drug-related rhabdomyolysis.

Case presentation

A man, in his early 30s, with no significant medical history or family history presented to the emergency room with a 2-week history of fatigue, and intermittent chest and abdominal pain associated with episodes of vomiting. He endorsed decreased appetite, dizziness and shortness of breath with exertion. The patient was haemodynamically stable, afebrile and physical examination revealed mild epigastric tenderness. He had no myalgias, weakness or changes in his urine.

Investigations

Initials laboratory testing revealed an AKI (creatinine 2.04 mg/dL), transaminitis (figure 1: Aspartate Transaminase [AST] 586 IU/L, Alanine Transaminase [ALT] 82 IU/L) and mild leucopenia (white cell count 4.2 x 10ˆ9/L). Urinalysis returned positive for blood with one red cell per high power field. Nasopharyngeal swab nucleic acid amplification (NAA) returned negative for influenza A and B, respiratory syncytial virus and SARS-CoV-2. A CT abdomen/pelvis without oral or intravenous contrast reported only non-specific, mildly prominent inguinal lymph nodes. The lung bases were clear, there was no pleural effusion and the liver was normal in size without focal abnormality on imaging.

Figure 1.

Transaminitis with trend in Asparate Transaminase [AST]/Alanine Transaminase [ALT] (graph created by AAA).

Given the non-specific symptomatology and unclear aetiology of the patient’s AKI with transaminitis, he was admitted for further evaluation. Acute hepatitis panel returned negative for hepatitis A, B and C viruses. Hepatitis C quantitative NAA also was negative. CK was significantly elevated at 121 200 U/L (normal <195).

Differential diagnosis

In exploring his differential diagnosis, further history was obtained. The patient denied use of prescription or over the counter medications such as non-steroidal anti-inflammatory drug use, illicit drugs, alcohol, herbals or supplements. There was no recent significant strenuous exercise activity or trauma. Given his unusual presentation with lack of myopathy, there was still no clear aetiology or inciting event to result in clinically significant rhabdomyolysis with an AKI and transaminitis, this prompted broader laboratory testing (table 1).

Table 1.

Comprehensive laboratory testing evaluating infectious versus non-infectious aetiology of rhabdomyolysis

Investigation	Result
Urine drug screen for amphetamines, barbiturates, benzodiazepines, cannabinoid, cocaine, ethyl-alcohol, methadone, opiate, fentanyl, oxycodone	Negative
Hepatitis panel: Hepatitis B surfaceantigen Hepatitis B core IgM Hepatitis C antibody Hepatitis C nucleic acid amplification Hepatitis A IgM antibody	Negative
Syphilis	Treponema pallidum antibody: reactive Rapid Plasma Reagin (RPR) titre: non-reactive Screen and Treponema pallidum confirmation was positive but rapid plasma reagin was negative.
Urine screen nucleic acid amplification for Chlamydia trachomatis, Neisseria gonorrhoea and Trichomonas vaginalis	Negative
Cytomegalovirus (CMV) IgG antibody	Positive
Echovirus serologies	Negative
Parvovirus B19 IgM	Negative
Coxsackie B serology	Negative
Throat culture for strep pyogenes	Negative
EBV Viral Capsid Antigen (VCA) antibody panel	IgG>600 U/mL (Neg<18 U/mL) Nuclear Ab IgG 144 U/mL (Neg<18 U/mL) (indicating past infection)
Aldolase	10.2 U/L (3.3–10.3)
Sedimentation rate by modified Westergren	26 mm/hour (0–15 mm/hour)
Lactate dehydrogenase	1630 IU/L (126–266 IU/L)
Thyroid Stimulating Hormone	1.2 MIU/L (0.27–4.20 MIU/L)
Immunoglobulins IgG level	722 mg/dL (603–1613 mg/dL)
Vitamin B12	233 PG/mL (232–1245 pg/mL)
Cortisol random	14.8 μg/DL (04.–62.9 μg/dL)
Antinuclear antibody	Negative
Antimitochondrial antibody	Negative
Antismooth muscle antibody	Negative
Liver kidney microsomal antibody	Negative
Alpha-1 antitrypsin	163 mg/dL (90–200 mg/dL)
Acetaminophen level	<5 μg/mL (≤35.0 mμg/mL)
Complement level	Not done

EBV, Epstein-Barr virus.

Treatment

On day 3 of his hospitalisation, the patient’s AKI was improving with intravenous hydration and CK was downtrending (figure 2). However, his fatigue and anorexia failed to improve. The patient attributed his decreased appetite to discomfort with swallowing. HIV testing 1 month prior to presentation was negative, however, the patient consented to repeat testing. He was started on nystatin empirically with notable improvement in his symptoms.

Figure 2.

Trend in non-cardiac creatine kinase (graph created by AAA).

Outcome and follow-up

Fourth-generation HIV testing returned positive documenting seroconversion. The patient’s HIV viral load was elevated at >10 000 000 copies/mL, and CD₄ count was 249 cells/UL. A diagnosis of acute HIV-related rhabdomyolysis was tentatively established while broader laboratory testing was in progress, such as aldolase, antinuclear antibody screen with reflex, Epstein-Barr virus antibody panel, coxsackie B antibodies, parvovirus B19 IgM antibody.

CK began to improve prior to the initiation of antiretroviral therapy. The patient was counselled, started on Biktarvy and discharged to follow up with infectious disease. His transaminases and CK normalised on follow-up laboratory testing 3 weeks later. The patient remained adherent to antiretroviral therapy and his HIV RNA PCR remained non-detectable at 4 months. He was able to return to work with no limitations and remained asymptomatic. The patient did not provide a clear sexual history.

Discussion

There are several aetiologies of rhabdomyolysis and differentials can be assessed based on traumatic versus non-traumatic, infectious versus non-infectious.^{2 3} Rhabdomyolysis is rarely associated with acute HIV infection alone.⁴ Early HIV infection or ‘acute retroviral syndrome’ typically occurs 2–6 weeks after exposure and is characterised by mild influenza-like illness, often unrecognised, to a more severe constellation of symptoms including fever, sore throat, fatigue, anorexia, myalgias/arthralgias, diarrhoea, rash and adenopathy. Laboratory abnormalities in the acute phase include lymphopenia, thrombocytopenia and elevated hepatic transaminases.

As described by McDonagh et al, most of the rhabdomyolysis and acute HIV case reports had some drawbacks as HIV could not definitively be the sole aetiology of rhabdomyolysis due to incomplete investigation of potential causes.^{5 6} We believe this case demonstrates a reasonable evaluation and diagnostic workup to exclude other non-infectious and infectious causes in order to rule out a multifactorial aetiology for rhabdomyolysis. Given the negative HIV test 1 month prior and seroconversion documented with initial HIV screen positive and a negative confirmatory antibody test and very high HIV-1 viral load of >10 million copies/mL, his rhabdomyolysis was attributed to acute HIV. Cytomegalovirus (CMV) serum NAA was not pursued due to his CMV IgG being positive. It should be noted that in immunosuppressed subjects, the appearance of CMV viraemia can be observed even if anti-CMV antibodies are present. As such, serum CMV NAA testing should be pursued in order to evaluate for viraemia as part of a thorough diagnostic workup.

Immune-mediated mechanisms activated by HIV itself were proposed as a mechanism for skeletal muscle involvement in HIV. Inflammatory cell infiltration into the muscle leads to muscle cell injury and breakdown.⁷

Asymptomatic mild transaminitis is reported in up to 21% of patients with acute HIV infection. The aetiology of the patient’s transaminitis can be related to the acute HIV infection itself and/or as a direct result of the non-traumatic rhabdomyolysis. This transaminitis can be related to liver injury by apoptosis of hepatocytes through the interaction of HIV envelope glycoprotein gp120 with CXCR4 on hepatocytes via G-protein signalling.⁸ Elevation of ALT is relatively specific to the liver; however, the patient’s AST was also significantly elevated suggesting a musculoskeletal origin such as rhabdomyolysis. Based on the enzyme trend (figures 1 and 2) the AST concentrations decreased in parallel to the CK, supporting the theory that skeletal muscle injury due to rhabdomyolysis may be a significant source of AST elevation in this patient.

This case is unique as the patient did not have muscle pain, cramps or muscle tenderness which is otherwise often seen in rhabdomyolysis. It is important to note that the HIV RNA qualitative PCR is now included as a part of the current Centers for Disease Control and Prevention HIV testing algorithm, making it easier to diagnose acute HIV, when previously the P24 antigen or HIV PCR had to be separately ordered.^{9 10}

Despite myalgias being a common symptom of the acute HIV infection, rhabdomyolysis with significantly elevated CK is an unusual finding. The management of rhabdomyolysis associated with acute HIV is not different from rhabdomyolysis due to other causes, however, it is important to remember to include HIV testing in the diagnostic approach as the hyperinfectious stage of primary HIV can easily be missed.

Patient’s perspective.

I knew something was off, that’s why I got tested a month ago. I still felt tired, I didn’t think the HIV test would come back positive.

Learning points.

• The most common aetiology of rhabdomyolysis is exercise/trauma. In the absence of a clear inciting aetiology, a broad differential diagnosis with laboratory testing to assess infectious versus non-infectious aetiologies is paramount.

• Rhabdomyolysis is an uncommon presentation of acute HIV infection and it is important to include testing especially in the potential seroconversion period.

• HIV can uncommonly cause a mild transaminitis and testing should be included when evaluating abnormal liver function profile.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).