Positive Murphy’s Sign Differential Diagnosis: Recognizing Fitz-Hugh-Curtis Syndrome

Right upper quadrant (RUQ) abdominal pain is a common presentation in clinical practice, prompting a broad differential diagnosis. While acute cholecystitis, often indicated by a positive Murphy’s sign, frequently tops the list, clinicians must consider less prevalent yet critical conditions. Fitz-Hugh-Curtis Syndrome (FHCS), a perihepatitis typically associated with pelvic inflammatory disease (PID), represents one such diagnostic challenge. This article delves into FHCS, emphasizing its importance in the differential diagnosis of RUQ pain, particularly when a positive Murphy’s sign is present but gallstones are absent. We aim to provide a comprehensive understanding of FHCS for healthcare professionals to enhance diagnostic accuracy and patient care.

Understanding Fitz-Hugh-Curtis Syndrome

Fitz-Hugh-Curtis Syndrome, also known as perihepatitis, is characterized by inflammation of the liver capsule and adjacent peritoneum, predominantly in the RUQ. It is most commonly a complication of ascending genital infections, specifically pelvic inflammatory disease (PID), in women. While the liver parenchyma itself is not primarily affected, the inflammation of the surrounding tissues can lead to significant pain and diagnostic confusion. The hallmark pathological finding is often described as “violin string adhesions” between the liver capsule and the anterior abdominal wall or diaphragm, although these are typically observed during laparoscopic examination and not always clinically relevant for initial diagnosis.

FHCS is predominantly associated with Chlamydia trachomatis and Neisseria gonorrhoeae, the same pathogens commonly implicated in PID. These bacteria ascend from the lower genital tract, causing infection and inflammation of the pelvic organs, and in some cases, extend to the perihepatic space. Other bacteria, including anaerobes and Mycoplasma genitalium, have also been implicated, suggesting a broader range of potential causative agents.

Clinical Presentation and Diagnostic Challenges

The cardinal symptom of FHCS is RUQ abdominal pain. This pain often has pleuritic characteristics, meaning it is exacerbated by movement, deep breathing, or coughing. Patients may describe the pain as sharp, stabbing, or aching. The intensity can range from mild to severe, sometimes mimicking the pain of acute cholecystitis or other acute abdominal conditions.

A significant diagnostic challenge arises from the fact that patients with FHCS can present with a positive Murphy’s sign, a clinical finding traditionally associated with gallbladder disease. Murphy’s sign is elicited by palpating the RUQ deeply while the patient takes a deep breath. Pain and inspiratory arrest during this maneuver are considered a positive Murphy’s sign, suggesting gallbladder inflammation. However, in FHCS, the inflammation of the perihepatic peritoneum can also cause tenderness and pain upon palpation in the RUQ, leading to a false positive Murphy’s sign in the context of biliary pathology.

This diagnostic mimicry can lead to unnecessary investigations and even surgical explorations if FHCS is not considered in the differential diagnosis. As highlighted in the original case report, the patient presented with RUQ pain, exacerbated by movement and breathing, and exhibited a positive Murphy’s sign, initially raising suspicion for acute appendicitis and gallbladder issues.

Figure 1. Abdominal ultrasonography demonstrating gallbladder distention without gallstones, and no biliary duct dilation, ruling out acute cholecystitis in this case but not Fitz-Hugh-Curtis Syndrome.

Differential Diagnosis of RUQ Pain with Positive Murphy’s Sign

When a female patient presents with RUQ pain and a positive Murphy’s sign, the initial differential diagnosis typically includes:

• Acute Cholecystitis: Inflammation of the gallbladder, most commonly due to gallstones obstructing the cystic duct. This is the most frequent cause of a true positive Murphy’s sign.
• Cholelithiasis with Biliary Colic: Gallstones in the gallbladder or bile ducts causing intermittent pain, but usually without persistent Murphy’s sign unless complicated by cholecystitis.
• Ascending Cholangitis: Infection of the bile ducts, often associated with biliary obstruction. This is a more severe condition usually accompanied by fever and jaundice (Charcot’s triad).
• Hepatitis: Inflammation of the liver, which can be viral, alcoholic, or drug-induced. Hepatitis may cause RUQ pain, but Murphy’s sign is less consistently positive and liver enzyme abnormalities are more prominent.
• Hepatic Abscess: A collection of pus within the liver, typically due to bacterial or amoebic infection. This is less common but can cause RUQ pain and systemic illness.
• Right-sided Pneumonia or Pleural Effusion: Pulmonary conditions can sometimes refer pain to the RUQ and cause tenderness.
• Ectopic Pregnancy (ruptured): In women of reproductive age, a ruptured ectopic pregnancy can present with abdominal pain, although it is usually more generalized or lower abdominal pain. RUQ pain is less typical but possible with hemoperitoneum tracking upwards.
• Appendicitis (retrocecal): Although typically presenting in the right lower quadrant, a retrocecal appendix can cause RUQ pain.
• Fitz-Hugh-Curtis Syndrome (Perihepatitis): Inflammation of the liver capsule associated with PID, as discussed in detail.

It is crucial to systematically rule out these conditions based on clinical history, physical examination, laboratory investigations, and imaging studies.

Table 1. Differential diagnosis of right upper quadrant abdominal pain, highlighting the importance of considering Fitz-Hugh-Curtis Syndrome in sexually active women without gallstones.

Diagnostic Approach to FHCS

The diagnosis of FHCS is primarily clinical, relying on a combination of factors:

1. Clinical Context: Young, sexually active women are at higher risk. A history of sexually transmitted infections, PID, or risk factors for STIs should raise suspicion. Symptoms suggestive of PID, such as pelvic pain, vaginal discharge, or dyspareunia, may or may not be present concurrently with RUQ pain. Crucially, the RUQ pain in FHCS is often pleuritic and exacerbated by movement.

2. Exclusion of Biliary Pathology: Imaging, particularly abdominal ultrasound, is essential to rule out gallstones, cholecystitis, and biliary obstruction. As seen in the case report, ultrasound can demonstrate gallbladder distention but absence of gallstones or biliary dilatation, making acute cholecystitis less likely. CT scans can further evaluate for other intra-abdominal pathologies, like appendicitis, and may show perihepatic inflammation, although this is not a specific finding for FHCS.

3. Microbiological Evidence of Infection: Testing for Chlamydia trachomatis and Neisseria gonorrhoeae is paramount in suspected FHCS. Urine PCR testing is a sensitive and non-invasive method. Positive results strongly support the diagnosis, especially in the appropriate clinical setting. However, a negative test does not entirely rule out FHCS, as other pathogens can be involved, or the infection may have cleared from the genitourinary tract while perihepatitis persists.

4. Elevated Inflammatory Markers: While not specific, elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) may be present, reflecting the inflammatory process. White blood cell count is typically normal or mildly elevated. Liver function tests are usually normal or only mildly abnormal, helping to differentiate FHCS from hepatitis.

Laparoscopy can visualize the characteristic “violin string adhesions,” but it is rarely indicated for diagnosis. Diagnosis should be made clinically to avoid invasive procedures.

Treatment and Management

The treatment of FHCS focuses on antibiotic therapy to eradicate the underlying infection. Empirical antibiotic regimens should cover Chlamydia trachomatis, Neisseria gonorrhoeae, and potentially anaerobic bacteria, given the polymicrobial nature of PID in some cases. Recommended antibiotic regimens, often derived from CDC guidelines for PID treatment, include:

• Ceftriaxone (intramuscularly or intravenously) plus Doxycycline (oral) with or without Metronidazole (oral).
• Cefotetan (intravenously) or Cefoxitin (intravenously) plus Doxycycline (oral).
• Clindamycin (intravenously) plus Gentamicin (intravenously).

Oral regimens may be appropriate for outpatient management of milder cases, typically involving doxycycline and often ceftriaxone or azithromycin. The duration of treatment is usually 10-14 days.

Table 2. Example antibiotic regimens for the treatment of Fitz-Hugh-Curtis Syndrome, adapted from PID treatment guidelines. Local guidelines and antibiotic resistance patterns should inform specific choices.

Pain management is also crucial. Analgesics, including NSAIDs or opioids for severe pain, can be used. Symptoms typically improve within a few days of starting appropriate antibiotic therapy. Adhesions may persist even after successful treatment, but they often do not cause long-term symptoms. In rare cases, persistent chronic abdominal pain due to adhesions may require laparoscopic adhesiolysis.

Furthermore, it is essential to screen and treat sexual partners to prevent reinfection and further spread of STIs. Patient education on safe sexual practices is also a vital component of management.

Conclusion

Fitz-Hugh-Curtis Syndrome is an important differential diagnosis to consider in women presenting with right upper quadrant abdominal pain, particularly when a positive Murphy’s sign is elicited but gallstones are absent. Clinicians should maintain a high index of suspicion for FHCS in sexually active women with RUQ pain, especially those with risk factors for or history of STIs or PID. A thorough diagnostic approach, including exclusion of biliary and other abdominal pathologies, microbiological testing for Chlamydia trachomatis and Neisseria gonorrhoeae, and appropriate antibiotic treatment, is crucial for effective management. Recognizing FHCS promptly not only alleviates patient symptoms but also prevents potential long-term complications associated with untreated PID and STIs. By considering FHCS in the differential diagnosis of RUQ pain and positive Murphy’s sign, healthcare providers can deliver more accurate and timely care to women affected by this condition.

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