Rhabdomyolysis Secondary to Reactivated Herpes Simplex Virus Type 1 Coinfected with Klebsiella pneumoniae in an Elderly Patient: A Case Report

Technical Summary: Rhabdomyolysis Secondary to Reactivated HSV-1 Coinfected with Klebsiella pneumoniae in an Elderly Patient

Problem Statement
Rhabdomyolysis (RM), a syndrome characterized by skeletal muscle breakdown and the release of cellular contents, is a serious condition often leading to acute kidney injury (AKI) and multi-organ dysfunction. While infectious etiologies account for 5%–31% of RM cases, typical pathogens include Legionella, Streptococcus, and influenza virus. Klebsiella pneumoniae rarely induces RM directly, with existing literature limited to highly virulent strains or cases secondary to liver abscesses. Similarly, Herpes Simplex Virus Type 1 (HSV-1) induced RM is typically associated with severe muscle contractions following seizures from viral encephalitis.

A significant diagnostic challenge exists in elderly, bedridden, and cognitively impaired patients (e.g., those with dementia). These patients often lack the classic symptoms of RM, such as severe myalgia and tea-colored urine, presenting instead with nonspecific signs like low-grade fever and fatigue. Consequently, occult RM is frequently missed, leading to delayed intervention and increased mortality. To date, no comprehensive case reports have described RM triggered specifically by the coinfection of reactivated latent HSV-1 (without encephalitis) and Klebsiella pneumoniae.

Methodology
This case report details the clinical course of a 90-year-old patient with vascular dementia, long-term bedridden status, and a history of severe pneumonia. The diagnostic approach relied on:

1. Metagenomic Next-Generation Sequencing (mNGS): Performed on bronchoalveolar lavage fluid (BALF) at an outside hospital and subsequently on nebulized sputum at the current facility. This allowed for the identification and quantification of pathogen reads (HSV-1 and K. pneumoniae) to distinguish active proliferation from asymptomatic colonization.
2. Serial Biomarker Monitoring: Dynamic tracking of Creatine Kinase (CK), CK-MB, myoglobin, and inflammatory markers (CRP, PCT) to assess muscle injury and infection severity.
3. Serological Analysis: Testing for HSV-1 IgG and IgM to determine the status of viral infection (reactivation vs. primary infection).
4. Exclusionary Diagnostics: Comprehensive testing to rule out other causes of RM, including autoimmune panels, other viral respiratory panels, and fungal/bacterial cultures.

Key Results

• Pathogen Identification: Initial BALF (June 10) detected low read counts of K. pneumoniae (13 reads) and HSV-1 (97 reads). Follow-up sputum mNGS (June 27) revealed a marked increase in pathogen load, with K. pneumoniae at 63,748 reads and HSV-1 at 23,010 reads. This significant elevation confirmed active pathogen proliferation rather than mucosal colonization.
• Clinical Presentation: The patient presented with fever, cough, and a red maculopapular rash on the hip but lacked typical RM symptoms like muscle pain.
• Laboratory Findings: Admission labs showed elevated CK (1,593 U/L) and myoglobin (>500 ng/mL). Despite the absence of myalgia and normal urinalysis results, the combination of elevated muscle enzymes and significantly elevated serum myoglobin confirmed a diagnosis of cryptic rhabdomyolysis. HSV-1 serology showed strongly positive IgG with negative IgM, consistent with latent reactivation.
• Therapeutic Outcome: The patient was treated with aggressive fluid resuscitation (2,500–2,800 mL/day) to facilitate myoglobin clearance, piperacillin-tazobactam for K. pneumoniae, and nutritional/immune support. Notably, acyclovir was withheld due to the high risk of myoglobin-induced acute tubular injury and the drug's renal clearance profile. Following treatment, CK and inflammatory markers normalized, and the patient's clinical status improved without developing AKI or multi-organ failure.

Key Contributions
This paper reports the first documented instance of occult rhabdomyolysis driven by the concurrent reactivation of latent HSV-1 (in the absence of encephalitis or seizures) and Klebsiella pneumoniae infection.

• Diagnostic Insight: It highlights the utility of mNGS in distinguishing active coinfection from colonization in complex, immunocompromised elderly patients.
• Clinical Observation: It documents that RM in elderly dementia patients can present with "cryptic" symptoms (fever, fatigue) rather than classic myalgia, necessitating a lower threshold for CK and myoglobin screening in this demographic.
• Therapeutic Strategy: The case provides evidence for a management approach prioritizing fluid resuscitation and targeted antimicrobial therapy while carefully weighing the risks of nephrotoxic antiviral agents (like acyclovir) in the setting of severe myoglobinuria.

Significance and Claims
The authors assert that this case represents a novel clinical entity: cryptic rhabdomyolysis induced by latent HSV-1 reactivation combined with K. pneumoniae infection. The paper claims that the mechanism likely involves a synergistic effect where K. pneumoniae endotoxins cause ischemia and energy metabolism impairment, while the viral infection triggers a cytokine storm and direct cytotoxicity, all exacerbated by the patient's frailty and immobility.

The primary significance of this work is a call to action for clinicians: in elderly, bedridden patients with dementia who present with fever and nonspecific weakness, routine testing for CK and myoglobin is essential to prevent missed diagnoses of rhabdomyolysis. Early identification through proactive laboratory monitoring is critical to preventing acute kidney injury and multi-organ failure in this vulnerable population. The authors conclude that dual-targeted management—combining pathogen-specific antimicrobial therapy with supportive care for RM—is necessary to improve outcomes in such complex mixed infections.