Primary human immunodeficiency virus type 1 infection in a patient with acute rhabdomyolysis.

Abstract: Primary human immunodeficiency virus type 1 (HIV-1) infection (acute retroviral syndrome) has been well characterized as a mononucleosis-like illness. Manifestations of HIV-1 infection such as pharyngitis, fever, morbilliform rash, myalgias, arthralgias, nausea, headache, emesis, and lymphadenopathy have been reported. Acute rhabdomyolysis has been reported as part of the acute retroviral syndrome on 11 different occasions. We report the case of a primary HIV-1 infection with acute rhabdomyolysis and review critically the other case reports.

Key Words: HIV-1 seroconversion, primary HIV-1 infection, rhabdomyolysis

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Primary human immunodeficiency virus type 1 (HIV-1) infection is diagnosed through detection of a high plasma viral RNA level or the presence of plasma p24 antigen accompanied by a negative HIV-1 antibody test. (1) Rhabdomyolysis is defined as breakdown of striated muscle with release of myoglobin and other muscle constituents into the extracellular space. (2) Although the presence of urine myoglobin is mentioned as a feature of rhabdomyolysis, (3,4) the strict definition of the syndrome does not require myoglobinuria. Causes of rhabdomyolysis are numerous, including genetic disorders of metabolism, high fever, trauma, rheumatologic disorders, thyroid disorders, hypophosphatemia, alcohol or illicit drug use, and infections, most notably influenza virus types A and B, cytomegalovirus, echovirus, coxsackievirus, toxoplasmosis, Legionella species, Francisella tularensis, Streptococcus, Staphylococcus, and known HIV-1 infection. (2,5,6)

Discussion

Review of the world literature (4,7-16) yielded 11 case reports of acute rhabdomyolysis in association with primary HIV-1 infection. Table 1 displays the results of our literature search of rhabdomyolysis associated with primary HIV infection. We list the 15 cases reported by Joshi and Liu, (4) Chariot et al, (7) and Neves et al (8) because they are commonly referred to in the literature on this topic. However, they are clearly not cases of primary HIV infection.

Four other cases (9-12) listed in our table of putative primary HIV infection presenting as rhabdomyolysis have significant limitations. We argue that rhabdomyolysis cannot be attributed to primary HIV infection in these cases. Two reports of acute rhabdomyolysis and acute HIV infection are found in patients with acute coinfection with cytomegalovirus, (9,12) a known cause of acute rhabdomyolysis. (17) The case by de Leon et al (10) describes a 21-year-old IV drug user who developed acute rhabdomyolysis during primary HIV infection but lacked a urine toxicology screen to exclude concurrent heroin or cocaine abuse. In the case reported by Pedersen and Pedersen, (11) a 31-year-old man presented with fever and rhabdomyolysis leading to renal failure but also had alcohol abuse, Staphylococcus aureus infection, and [beta]-hemolytic streptococcal infection, all known causes of rhabdomyolysis.

An additional four cases (13-16) in Table 1 have lesser limitations, such that we would accept primary HIV infection as a likely cause of the acute rhabdomyolysis. The case described by Rastegar et al (13) involves a history of alcohol use in a 51-year-old man but lacks an alcohol level and a phosphorus level. One could argue that alcohol may have been a confounding factor with the HIV infection in causing acute rhabdomyolysis in this case. Although the authors in this report speculate that the urine myoglobin result was a false-negative, one should note that the presence of myoglobinuria is not required for the diagnosis of rhabdomyolysis. Guillaume et al (14) describe the case of a 42-year-old man who presented with rhabdomyolysis, myocarditis, and polymyositis who was subsequently found to have a primary HIV infection. This study does not mention other causes of rhabdomyolysis, specifically a phosphorus level, an alcohol level, or a history pertaining to alcohol use. In an article by del Rio et al, (15) although describing a 29-year-old man with rhabdomyolysis, nephrotic syndrome, acute tubular necrosis confirmed by renal biopsy, and primary HIV infection, a toxicology screen and phosphorous level are not mentioned. Similarly, Mahe et al (16) presented the case of an 18-year-old man with primary HIV infection and rhabdomyolysis without mention of alcohol use, blood alcohol level, or toxicology screen.

There are many reports of high fever associated with rhabdomyolysis, but it is difficult to sort out whether fever per se or the underlying condition is responsible for the rhabdomyolysis. (2,18-20) Of the 11 case reports discussed here, only de Leon et al(10) and del Rio et al(15) listed a temperature greater than 39[degrees]C. Our patient's maximal temperature was 38.7[degrees]C, and he only had two temperature readings greater than 38.4[degrees]C. The uncertainty in previous reports between fever and rhabdomyolysis does not allow us to state so unequivocally, but we do not believe our patient's fever contributed significantly to his rhabdomyolysis.

Our review of the world literature describing primary HIV-1 infection presenting with acute rhabdomyolysis showed that instead of 23 cases, only four are well supported. (13-16) Thus, we report our case as the fifth case of acute rhabdomyolysis with primary HIV-1 infection and draw attention to its lack of confounding variables. We suggest that the diagnosis of primary HIV-1 infection be considered in patients at risk who present with acute rhabdomyolysis.

I am going your way, So let us go hand in hand ... For soon death, the kind old nurse, Will come back and rock us all to sleep. Let us help one another while we may.

--William Morris

Table 1.  Cases of HIV-1 infection associated with acute rhabdomyolysis
(a)
        Reference           Age  Sex          Symptoms

Joshi and Liu, 2000 (4)     42    M   Not known

                            33    M   Not known

                            43    M   Not known

                            47    M   Not known

                            72    M   Not known

                            38    M   Not known

                            73    M   Not known

Chariot et al, 1994 (7)     28    M   Fever, myalgias

                            33    M   Fever, myalgias

                            68    M   Myalgias

                            30    M   Fever, diffuse pain

                            20    M   Renal failure,
                                      pneumonia

                            35    M   Fever, weakness

                            43    M   Myalgias

Neves et al, 1991 (8)       25    F   Myalgias, weakness

Schindler and Neftel, 1990  18    F   Pancytopenia, hephritis, myositis,
(9)                                   hepatitis

de Leon et al, 1991 (10)    21    M   Fever, myalgias

Pedersen and Pedersen,      31    M   Fever, rash, oral ulcers
1996 (11)

Ragnaud et al, 1995 (12)    20    M   Fever, myalgias, rhinopharyngitis

Rastegar et al, 2001 (13)   51    M   Lower extremity pain

Guillaume et al, 1995 (14)  42    M   Fever, myalgias

del Rio et al, 1990 (15)    29    M   Fever, sore throat, renal failure

Mahe et al, 1989 (16)       18    M   Myalgias, abdominal pain, sore
                                      throat

        Reference           CPK peak     Additional features

Joshi and Liu, 2000 (4)     110,000 U/L  Heroin, barbiturate use,
                                         trauma

                            160,000 U/L  Sepsis

                             88,940 U/L  Pneumonia, alcohol use

                             98,430 U/L  Sepsis, alcohol and
                                         cocaine use

                             19,720 U/L  Sepsis, alcohol use

                             21,260 U/L  Alcohol use, zidovudine
                                         treatment

                             42,970 U/L  Sepsis, alcohol and
                                         cocaine use, zidovudine
                                         treatment

Chariot et al, 1994 (7)      22,000 U/L

                             60,000 U/L  Benzodiazepine,
                                         neuroleptic drug use

                              7,600 U/L  Zidovudine, didanosine
                                         treatment

                              2,600 U/L  Cerebral toxoplasmosis,
                                         sulfadiazine treatment

                             15,000 U/L  Sepsis

                             11,000 U/L  Cryptococcal infection

                              2,400 U/L  Mycobacterial and CMV
                                         infections

Neves et al, 1991 (8)         2,359 U/L

Schindler and Neftel, 1990      775 U/L  Coinfection with CMV
(9)

de Leon et al, 1991 (10)      1,833 U/L  Heroin use

Pedersen and Pedersen,        1,323 U/L  Alcohol use
1996 (11)

Ragnaud et al, 1995 (12)     11,016 U/L  Coinfection with CMV

Rastegar et al, 2001 (13)    32,720 U/L  Alcohol use

Guillaume et al, 1995 (14)   63,800 U/L  Myopericarditis

del Rio et al, 1990 (15)      4,224 U/L  Acute tubular necrosis on
                                         renal biopsy

Mahe et al, 1989 (16)         5,750 U/L

        Reference                          Limitations

Joshi and Liu, 2000 (4)     Known HIV-positive

                            Known HIV-positive

                            Known HIV-positive

                            Known HIV-positive

                            Known HIV-positive

                            Known HIV-positive

                            Known HIV-positive

Chariot et al, 1994 (7)     Known HIV-positive

                            Known HIV-positive

                            Known HIV-positive

                            Not primary HIV infection

                            Known HIV-positive

                            Known HIV-positive

                            Known HIV-positive
Neves et al, 1991 (8)       Not primary HIV infection
Schindler and Neftel, 1990
(9)

de Leon et al, 1991 (10)    No toxicology screen

Pedersen and Pedersen,      Staphylococcus and Streplococcus infections
1996 (11)

Ragnaud et al, 1995 (12)    No toxicology screen

Rastegar et al, 2001 (13)   No blood alcohol level, no phosphorus level

Guillaume et al, 1995 (14)  No history regarding alcohol use

del Rio et al, 1990 (15)    No toxicology screen, no phosphorus level

Mahe et al, 1989 (16)       No history regarding alcohol use, no
                             toxicology screen, no blood alcohol level

(a) HIV-1, human immunodeficiency virus Type 1; CPK, creatine
phosphokinase: M, male: F, female: CMV, cytomegalovirus.
(b) Joshi and Liu report CPK in U/dl. For comparison purposes, we have
converted these values to U/L.

Acknowledgments

We thank Thomas A. Rakowski, MD, for reviewing the manuscript and Linda Hansen, administrative assistant at the Royal Danish Embassy, Washington, DC, for assistance with translating reference 11.

From the Department of Medicine, Georgetown University Medical Center, Washington, DC.

Reprint requests to Robert P. Holman, MD. Virginia Hospital Center-Arlington, 1715 N. George Mason Drive, Suite 108, Arlington, VA 22205. Email: [e-mail]

Accepted April 23, 2003.

Copyright [c] 2003 by The Southern Medical Association

0038-4348/03/9610-1027

References

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4. Joshi MK, Liu HH. Acute rhabdomyolysis and renal failure in HIV-infected patients: Risk factors, presentation, and pathophysiology. AIDS Patient Care STDS 2000;14:541-548.

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6. Gherardi R, Baudrimont M, Lionnet F, et al. Skeletal muscle toxoplasmosis in patients with acquired immunodeficiency syndrome: A clinical and pathological study. Ann Neurol 1992;32:535-542.

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RELATED ARTICLE: Case Report

Our case involved a 33-year-old Lebanese homosexual man who presented with fever, chills, sore throat, lower extremity pain, maculopapular rash, nausea, emesis, and headache. He did not use prescription medications, herbals/supplements, recreational drugs, or alcohol. He denied recent exercise or trauma.

Vital signs demonstrated a maximum temperature of 101.8[degrees]F, a heart rate of 125 beats/min, a blood pressure of 130/70 mm Hg, and a respiratory rate of 15 breaths/min. His examination was unremarkable except for a macular rash on his forehead and back. He had no lymphadenopathy, oral lesions or exudate, cardiac murmurs, hepatosplenomegaly, muscle tenderness, joint edema, or neurologic deficits.

Laboratory studies demonstrated the following: blood urea nitrogen, 9 mg/dl: creatinine, 0.8 mg/dl; calcium, 7.2 mg/dl; magnesium, 1.5 mg/dl; phosphorus, 3.0 mg/dl; aspartate aminotransferase, 321 U/L; alanine aminotransferase, 98 U/L; white blood cell count, 2,700/ [mu]l; and platelet count, 9,600/[mu]l. Creatine phosphokinase was initially 12,006 U/L and peaked at 18,840, the fractionation of which was 100% MM. Urine myoglobin was positive at 2.1 [mu]g/ml. Urine dipstick showed protein and large blood with one red blood cell per high-power field. Urine toxicology screen was negative, excluding alcohol and heroin. Lumbar puncture and cerebrospinal fluid studies were unremarkable. The patient's serum thyrotropin level was within normal limits, and blood and urine cultures remained negative. Further acute viral serologies were negative, including titers for Leptospira; coxsackievirus; echovirus; and hepatitis A, B, and C. Monospot and Group A streptococcal screens were negative. Positive immunoglobulin G antibodies were found to parvovirus, cytomegalovirus, and Epstein-Barr virus. HIV-1 antibody was negative, but HIV RNA polymerase chain reaction (viral load) showed>750,000 copies/ml. Convalescent antibody titers at 4 weeks against Leptospira, echovirus (Types 4,7,9,11, and 30), and coxsackievirus (B1-6) were all negative. Our case clearly exemplified primary HIV-1 infection with prominent acute rhabdomyolysis.

RELATED ARTICLE: Key Points

* Primary human immunodeficiency virus type 1 (HIV-1) infection is diagnosed through detection of a high plasma viral RNA level or the presence of plasma p24 antigen accompanied by a negative HIV-1 antibody test.

* Rhabdomyolysis is defined as breakdown of striated muscle with release of myoglobin and other muscle constituents into the extracellular space.

* Cause of rhabdomyolysis are numerous, including genetic disorders of metabolism, high fever, trauma, rheumatologic disorders, thyroid disorders, hypophosphatemia, alcohol or illicit drug use, and infection.

* Recognition of primary HIV-1 infection can provide an opportunity for counseling and early antiretroviral therapy.

Cara A. McDonagh, MD, and Robert P. Holman, MD