Abstract
Q fever, caused by Coxiella burnetii, is a zoonotic infection with highly variable clinical manifestations, often leading to diagnostic delays. Although typically associated with livestock exposure and presenting with nonspecific febrile illness or hepatitis, its clinical spectrum is broad. We report an unusual case of a 53-year-old previously healthy male who presented with high-grade fever, epigastric pain radiating to both upper quadrants, marked jaundice, severe acute kidney injury, and dark urine. Initial imaging revealed bilateral perinephric and periureteral stranding, gallbladder wall edema, and absence of biliary obstruction, raising concern for urinary and hepatobiliary pathology. Serologic testing for viral hepatitis and multiple bacterial pathogens was negative. Persistent cholestatic abnormalities and systemic symptoms prompted an expanded infectious workup, which revealed positive Coxiella burnetii IgG and IgM. Doxycycline therapy resulted in rapid clinical improvement and progressive normalization of renal and hepatic parameters, confirming acute Q fever based on compatible clinical presentation, positive serology, exclusion of alternative diagnoses, and response to doxycycline. This case is notable for the coexistence of cholestatic jaundice, severe renal dysfunction, and urinary symptoms without pulmonary or classical hepatitic features, illustrating a rare phenotype of acute Q fever. Additionally, the absence of identifiable exposure risks underscores ongoing under recognition of this infection outside traditional high-risk settings. The patient’s favorable response to timely doxycycline treatment highlights the importance of considering Q fever in the differential diagnosis of febrile jaundice with multiorgan involvement. This report reinforces the value of broad infectious evaluation in atypical presentations and contributes to expanding clinical awareness of Q fever’s diverse manifestations.
Introduction
Q fever, a zoonosis caused by Coxiella burnetii, is found worldwide and spreads mainly by inhaling particles from infected animals during delivery. It is often unrecognized because of its variable and nonspecific clinical presentation. Even though it is predominantly linked to rural and occupational exposure, the majority of patients report no direct animal contact. In Lebanon, seroprevalence studies suggest significant population exposure despite limited reported clinical cases.1,2 Acute Q fever most commonly presents with fever of unknown origin. Atypical pneumonia and mild hepatitis are common, however overt jaundice is infrequent.3,4 Hepatic manifestation involves elevation of transaminases without significant bilirubin rise. Renal involvement is uncommon in acute Q fever and is more frequently described in chronic infection, particularly endocarditis associated glomerulonephritis. 5 There are few reports of jaundice or kidney injury in acute Q fever. Nevertheless, the presence of both concurrently is extremely rare.4,5 Diagnosis is usually delayed in patients with no known exposure, broad differential and unspecific symptoms. 6 Serological testing of IgM and IgG remains the diagnostic cornerstone, but they might be negative in early infection. 6 PCR testing can help early detection, particularly within the 2 weeks, however its sensitivity declines with time and after antibiotic introduction. 6 We describe a case of acute Q fever infection manifesting as severe cholestatic jaundice, acute kidney injury, dysuria along with bilateral perinephric stranding, in the absence of recognizable exposure. This unusual presentation expands the known clinical spectrum of Q fever and emphasizes the need for consideration in the diagnosis of atypical febrile syndrome.
Case Presentation
A 53-year-old previously healthy male presented to the emergency department with a complaint of epigastric pain radiating to the right and left upper quadrants associated with fever (39.1°C) and diffuse body aches of 4 days history. On review of systems, the patient reported dysuria and dark orange-colored urine. The patient denied recent travel, animal contact, sick contacts, occupational exposure to livestock, farming activities, abattoirs, or veterinary work. He also denied nausea, vomiting, diarrhea, changes in stool color, pruritus, or flank pain.
On physical examination, the patient was alert and hemodynamically stable but had marked scleral icterus and jaundice. Abdominal examination revealed a soft, mildly distended abdomen with no rebound tenderness on palpation; bowel sounds were normal. Murphy and McBurney signs were negative and there was no suprapubic or costovertebral angle tenderness.
Initial laboratory investigations (Table 1, Day 1) demonstrated acute kidney injury (AKI) and predominantly cholestatic liver injury pattern with elevation of bilirubin and GGT levels. Blood cultures were obtained and empiric piperacillin–tazobactam was initiated due to concern for severe infection and possible ascending urinary source. Moreover, as a workup for jaundice and elevated liver enzymes, hepatitis A, B, and C serologies were obtained to rule out active viral hepatitis (Table 1).
Daily Laboratory Orders and Results During Hospitalization.
Abbreviations: ALP, alkaline phosphatase; BUN, blood urea nitrogen; CO2, carbon dioxide; Crea, creatinine; CRP, C-reactive protein; D, direct; GGT, gamma-glytamyl transferase; INR, international normalized ratio; K, potassium; L, lymphocytes; LDH, lactate dehydrogenase; MAT, microscopic agglutination test; N, neutrophils; Na, sodium; PT, prothrombin time; PTT, partial thromboplastin time; SGOT, serum glutamic-oxaloacetic transaminase; SGPT, serum glutamic-pyruvic transaminase; T, total; WBC, white blood cells.
Given the combination of jaundice, right upper quadrant pain, and abnormal liver function test, a CT of the abdomen and pelvis without IV contrast was ordered to evaluate for hepatobiliary pathology, renal abnormalities, or any intra-abdominal source of infection (Table 2). The results demonstrated bilateral perinephric and periureteral stranding, initially raising concern for an ascending urinary infection, an under-distended gallbladder, a small amount of free fluid in the right lower quadrant, and normal kidney size without hydronephrosis or nephrolithiasis. Despite imaging findings suggestive of an ascending infection, sterile urine cultures, and the absence of hydronephrosis argued against bacterial pyelonephritis.
Summary of Imaging Results.
To further evaluate the biliary tree and exclude obstructive or biliary pathology and due to the persistence of bilirubin elevation, an magnetic resonance cholangiopancreatography (MRCP) was done on Day 3 of hospitalization (Table 2). The result was pertinent for discrete gallbladder wall edema without biliary obstruction, stones, or ductal dilation with a mildly dysmorphic liver; the gallbladder wall edema was interpreted as reactive in nature, given the absence of gallstones, biliary obstruction or cholecystitis and was considered a nonspecific finding associated with systemic inflammatory or infectious conditions.
The constellation of acute febrile illness, jaundice, AKI, dark-colored urine, and imaging findings of perinephric stranding and gallbladder wall edema, in the absence of obstructive biliary disease, raised suspicion for infectious etiologies. Accordingly, additional tests including microscopic agglutination test (MAT), Widal test, Brucella IgG and IgM, Coxiella burnetii phase II IgG and IgM (indirect immunofluorescence assay), Rose Bengal test, and Wright test were ordered. PCR testing for Coxiella burnetii was not available at our institution at the time of presentation.
On day 3 of hospitalization, Coxiella burnetii IgG and IgM returned positive. The diagnosis of acute Q fever was established based on compatible clinical presentation, positive phase II IgM and IgG serology (⩾1:16), excluding alternative diagnoses. Accordingly, piperacillin-tazobactam was switched to doxycycline 100 mg twice daily.
On Day 4 of hospitalization, laboratory work demonstrated progressive improvement in laboratory parameters, mainly creatinine, liver function tests and C-reactive protein (CRP). Also, fever began to space out with marked decrease in pain and myalgias as reported by the patient. The patient was discharged on oral doxycycline to complete a 14-day course.
At outpatient follow-up 4 weeks after discharge, serum creatinine returned to 1.3 mg/dL, total bilirubin normalized, and liver enzymes returned to baseline. The patient remained asymptomatic with no recurrence of fever or urinary symptoms.
Discussion
Coxiella burnetii, the causative agent of Q fever in humans—is a major zoonotic pathogen commonly linked to goats,7,8 as well as other livestock species and people. 7 Its capacity to trigger widespread outbreaks is attributed to its extremely low infectious dose, remarkable environmental persistence, and efficient airborne dissemination through aerosolised particles. 7 Human Q fever is believed to be substantially under-diagnosed because symptoms are nonspecific and clinical awareness remains limited. During the initial phase of infection, many individuals are asymptomatic or experience mild, flu-like manifestations such as fever, malaise, and myalgia.7,9 Populations in rural regions, where livestock also display elevated seroprevalence, tend to exhibit higher exposure rates. A review of 81 outbreaks documented from 1990 to 2022 across 27 countries showed substantial variation in size and duration. Most events occurred in community settings rather than classical occupational environments. Environmental contamination and windborne spread were frequently implicated, particularly in large outbreaks. Sheep were the most commonly identified reservoir. Collaboration between human and veterinary health authorities was uncommon, underscoring the need for better coordinated surveillance and response strategies. 10
Acute Q fever displays diverse laboratory abnormalities. White blood cell and platelet counts may be normal or altered, and liver enzymes are usually elevated even when bilirubin levels remain within normal limits. Cholestatic jaundice in acute Q fever is thought to result from immune-mediated cholestasis and granulomatous hepatitis rather than direct hepatocellular injury. 11
Cerebrospinal fluid often demonstrates mononuclear pleocytosis accompanied by increased protein. Chest radiographs may reveal multiple rounded or pleural-adjacent opacities and hilar lymphadenopathy. 12 Echocardiography can show valvular vegetations, although this occurs in only about half of chronic cases. Diagnostic confirmation primarily relies on serologic testing and PCR. The indirect immunofluorescent assay remains the gold standard, detecting IgG against phase I and phase II antigens. Acute infections are characterized by higher anti-phase II IgG, and a fourfold rise between acute and convalescent samples supports the diagnosis. Antibodies usually become detectable by the third week. PCR is especially helpful early in illness when antibodies are absent 13 and can be applied to several tissue types, ideally within the first 2 weeks of symptom onset. Culturing C. burnetii requires biosafety level 3 containment because of high infectivity. Chronic disease, including endocarditis, is identified through PCR, culture, or elevated anti–phase I IgG titers (⩾1:800). Imaging tools such as MRI, CT, and 18F-FDG PET/CT may assist in identifying vascular sites, prosthetic joint involvement, or endocarditis.12,13
In view of the patient’s clinical presentation with acute febrile illness, marked cholestatic predominant jaundice, acute kidney injury, and urinary abnormalities, several alternative diagnoses were considered. Viral hepatitis was excluded on the basis of negative hepatitis A, B, and C serologies. Leptospirosis was considered part of the workup given the combination of jaundice and renal dysfunction but was deemed unlikely in the setting of a nonreactive microscopic agglutination test. Obstructive biliary pathology was excluded based on the CT and magnetic resonance cholangiopancreatography which showed absence of biliary dilation or gallstones. Ascending urinary tract infection and pyelonephritis were initially suspected in light of perinephric stranding on imaging. However, sterile urine cultures, absence of hydronephrosis, and the lack of sustained response to broad spectrum antibiotics argued against this diagnosis. Sepsis-associated acute kidney injury was also part of our differential but was considered less likely given negative blood cultures and rapid clinical and biochemical improvement following doxycycline therapy.
Doxycycline 100 mg twice daily for 14 days is the recommended treatment for acute infection. Alternatives minocycline, TMP-SMX, or clarithromycin may be used when doxycycline is not an option. Pregnant patients with non-severe acute Q fever should receive TMP-SMX until 32 weeks’ gestation due to the higher fetal risks of untreated infection. 12 Folic acid supplementation and routine serologic monitoring during and after pregnancy are essential. Life-threatening infections may still require doxycycline. Chronic or persistent infections in pregnancy are also managed with TMP-SMX. 12
Chronic Q fever, particularly endocarditis, requires long-term therapy with doxycycline plus hydroxychloroquine 18 months for native valves and 24 months for prosthetic valves. Treatment success is marked by a fourfold reduction in IgG titers. 12 Hydroxychloroquine potentiates doxycycline by raising phagolysosomal pH; rifampin or ciprofloxacin may serve as substitutes when necessary. Surgical intervention is often compulsory in prosthetic valve disease. Antibiotics provide no benefit for Q fever fatigue syndrome. A whole-cell vaccine is available for high-risk groups in Australia but is not recommended in the United States. 12
This case is particularly unique because the patient presented with a constellation of hepatic, renal, and urinary findings marked cholestatic jaundice, severe AKI, and bilateral perinephric stranding yet without any clear biliary obstruction or typical exposure history, making the diagnosis of Q fever highly challenging. While previous reports have described cholestatic hepatitis or acute kidney injury individually in acute Q fever, their concurrent presentation without pulmonary involvement remains exceptionally uncommon. Most reported cases describe febrile hepatitis or pneumonia as the dominant presentation, whereas our patient manifested simultaneous multiorgan involvement with prominent urinary symptoms and imaging changes that initially suggested ascending infection. Additionally, the rapid biochemical deterioration followed by prompt improvement after doxycycline highlights the importance of early consideration of zoonotic infections even in the absence of classical risk factors. This case underscores the diagnostic value of broad infectious testing in atypical jaundice AKI syndromes and broadens the recognized clinical spectrum of acute Q fever presentation.
Conclusion
This case highlights an atypical presentation of acute Q fever manifesting with cholestatic jaundice, severe acute kidney injury, and urinary symptoms in the absence of biliary obstruction or classical exposure risks. The unusual constellation of laboratory and imaging findings initially suggested alternative hepatobiliary or urinary etiologies, delaying suspicion of zoonotic infection. Rapid clinical and biochemical improvement following doxycycline underscores the importance of early recognition and treatment. This case broadens the recognized clinical spectrum of acute Q fever by highlighting severe multiorgan involvement in the absence of classical exposure or pulmonary disease.
Footnotes
Acknowledgements
We would like to thank Dr. Hassan Mallat (Department of Infectious Disease, Nini Hospital) for his expertise in diagnosing and contributing to the management of Q fever.
Consent to Participate
A written informed consent was signed by the patient before submitting the manuscript.
Authors Contributions
Conceptualization, Mahmoud Othman; writing—original draft preparation, Karim Zodeh, Tya Youssef, Philippe Attieh, Mahmoud Othman; writing—review and editing, Karim Zodeh, Tya Youssef, Philippe Attieh, Mahmoud Othman; supervision, Mahmoud Othman; project administration, Mahmoud Othman. All authors have read and agreed to the published version of the manuscript.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.