Continuing Education Activity

Fitz-Hugh-Curtis syndrome is inflammation of the liver capsule with adhesion formation resulting in right upper quadrant pain. It is an uncommon, chronic manifestation of pelvic inflammatory disease affecting women of childbearing age. This activity describes the evaluation and treatment of this condition and highlights the role of the interprofessional team in aggressively managing affected patients.

Objectives:

• Describe the risk factors for developing Fitz-Hugh-Curtis syndrome.
• Outline the typical presentation of a patient with Fitz-Hugh-Curtis disease.
• Describe the typical studies that should be ordered in the evaluation of Fitz-Hugh-Curtis syndrome.
• Explain the importance of improving care coordination amongst the interprofessional team to enhance the management of patients with Fitz-Hugh-Curtis syndrome.

Introduction

Fitz-Hugh-Curtis syndrome (FHCS), or perihepatitis, is a chronic manifestation of pelvic inflammatory disease (PID).[1] It is described as an inflammation of the liver capsule, without the involvement of the liver parenchyma, with adhesion formation accompanied by right upper quadrant pain. A final diagnosis can be made through laparoscopy or laparotomy via direct visualization of violin string-like adhesions or through hepatic capsular biopsy and culture.

The syndrome was first illustrated by Stajano in 1920 in a non-English publication. In 1930 Curtis described adhesions between the anterior surface of the liver and the abdominal wall found during laparotomies in patients with atypical gallbladder attacks. He noted that while no other upper abdominal pathology was found, residual gonococcal tubal changes were frequently observed in the subjects.[2]

In 1934, Fitz-Hugh, Jr. described similar cases which had presented with right upper quadrant abdominal pain. Laparotomy showed unusual, localized peritonitis involving the anterior surface and edge of the liver and adjacent peritoneal surface of the diaphragm. After drainage, tube insertion smears from drained fluid showed gram-negative, intracellular, biscuit-shaped diplococci. It is now known, however, that the syndrome is not exclusive to gonococcal infection and has been reported in both sexes.[3]

Etiology

Fitz-Hugh-Curtis syndrome is a complication of PID. Microorganisms associated with PID are thought to spread through one of three ways:

1. Spontaneous ascending infection whereby microbes from the cervix or vagina travel to the endometrium, through the Fallopian tubes, and into the peritoneal cavity. Complications include endometritis, salpingitis, tubo-ovarian abscess, pelvic peritonitis, and FHCS.[4]
2. Lymphatic spread, such as infection of the parametrium from an intrauterine device
3. Hematogenous spread, such as with tuberculosis [5][6]

Epidemiology

PID is an ascending microbial infection involving the genital tract that affects sexually active women between 15 to 30 years of age. The United States experiences 750,000 cases of PID each year. FHCS is an uncommon manifestation of PID involving around 4% of adolescents. While many organisms are associated with FHCS, Chlamydia trachomatis is the most common pathogen involved.[7]

Pathophysiology

As described in the etiology section, FHCS is a complication of PID. Microorganisms associated with PID are thought to spread in one of three ways:

• Through spontaneous ascending infection, microbes from the cervix or vagina travel to the endometrium, through the Fallopian tubes, and into the peritoneal cavity. Complications include endometritis, salpingitis, tubo-ovarian abscess, pelvic peritonitis, and perihepatitis.
• Microbes can also spread via lymphatic channels, such as an infection of the parametrium from an intrauterine device.
• Finally, the hematogenous spread is also possible such as with tuberculosis. [8][9][10]

History and Physical

Typically, patients with FHCS are women of childbearing age who visit a hospital with complaints of acute pain or chronic tenderness in the right upper abdomen. A thorough history and a high index of suspicion are necessary to reach an appropriate diagnosis. Right upper quadrant abdominal pain is a symptom of myriad pathologies including, but not exclusive to, cholecystitis, pleurisy, right pyelonephritis, subphrenic abscess, or herpes zoster infection, making an assessment for FHCS particularly difficult.[11][1][12]

The evaluating physician who suspects FHCS should focus on high-risk behaviors and symptoms in the appropriate patient population. Risk factors to consider are age less than 25 years, age at first sexual encounter less than 15 years, history of PID, use of IUD or oral contraceptives, recent IUD insertions, and vaginal douching. Investigating a patient’s exposure to new, multiple, or symptomatic sex partners is also of paramount importance. Obtaining a complete past medical and past surgical history also may help narrow the differential further. 

Right upper quadrant abdominal pain is caused by perihepatic inflammation and adhesion formation between the anterior surface of the liver and the abdominal wall. The pain is usually worse with movement and breathing, thereby mimicking other acute abdominal pathologies. Patients also may complain of lower abdominal, pelvic, or back pain with varying degrees of severity. Other symptoms may include fevers, chills, nausea, vomiting, vaginal discharge, dyspareunia, dysuria, cramping, and postcoital bleeding.[5][13]

Physical exam findings may reveal the following:

• Vital signs: Fever greater than 38.3 C.
• Abdominal exam: Right upper quadrant tenderness, rebound tenderness, guarding, or a silent abdomen.
• Pelvic exam: Cervical motion tenderness, adnexal tenderness, uterine compression tenderness on bimanual examinations. Look for signs of lower genital tract infection such as cervical mucopus and cervical friability on speculum examination.[7]

Evaluation

The following are helpful in the evaluation of FHCS and PID.

Lab Tests

• Performing a pregnancy test will not only guide the choice of antibiotic therapy but also address the possibility of an ectopic pregnancy.
• Complete blood count (CBC) to assess for leukocytosis. Know, however, that only up to 50% of women with PID have a clinically significant leukocytosis. Blood cultures can vary and are generally negative in the setting of PID.
• Complete metabolic panel to assess for any electrolyte, renal, or hepatic derangements.
• Vaginal secretions can be assessed for leukorrhea.
• Quantitative culture for chlamydia along with gonorrhea and chlamydial DNA probes can aid in diagnosis.
• Other tests to consider include RPR, Hepatitis B & C, HIV, and urinalysis.

Radiological Findings

• CT scan will show increased perihepatic enhancement in the arterial phase, with a majority of patients also showing pelvic fat infiltration. Other findings associated with PID can be found: pyosalpinx, tubo-ovarian abscess, and fluid collection in the pelvic cavity.
• Transvaginal ultrasonographic scanning is a favorable option for cases in which a clinical picture of PID may be unclear. Findings can include hydrosalpinx, pyosalpinx endometritis, tubo-ovarian abscess, oophoritis, and ectopic pregnancy.
• MRI can show tubo-ovarian abscess, edematous tubes, or free pelvic fluid collections.

Procedural Findings

• Laparoscopy is the gold standard for diagnosing FHCS and PID. In the setting of PID, laparoscopy can show edema with exudates on tubal surfaces, ectopic pregnancy, or tubo-ovarian abscess. FHCS can be diagnosed directly via visualization of adhesions between the diaphragm and liver or liver and the anterior abdominal wall.
• An endometrial biopsy can show endometritis.

Treatment / Management

Treatment of HFCS coincides with the management of PID. The goals of treatment are to relieve symptoms, eradicate the infection, and minimize risks of long-term sequelae (infertility or ectopic pregnancy). As the diagnosis of PID may be challenging and the potential for serious complications is great, the CDC advises that physicians maintain a low threshold for aggressive treatment. Antibiotics are successful in up to 75% of cases, and most patients with PID can be managed as outpatients. Antibiotic therapy should be geared at covering the most common organisms, Chlamydia trachomatis, and Neisseria gonorrhoeae, as well as gram-negative organisms, anaerobes, and streptococci.[14]

Depending on the degree of suspicion, antibiotics regimens can be tailored for each patient. Most commonly, ceftriaxone and azithromycin are adequate for the control of gonococcal and chlamydial infections.[15] Current recommendations for complicated pelvic inflammatory disease include ceftriaxone, doxycycline, and metronidazole.[16]

Hospitalization should be considered for patients with the following conditions:

• Uncertain diagnosis
• Pregnancy
• Severe illness
• Pelvic abscess on imaging
• Inability to tolerate anything by mouth
• Immunodeficiency
• Failure to improve after 72 hours of therapy

Patients with persistent symptoms of fever, chills, or cervical motion tenderness after 72 hours of treatment should be reevaluated for possible surgical intervention. Diagnostic laparoscopy is warranted in the setting of HFCS for symptomatic adhesiolysis and PID with goals of conserving reproductive potential with abscess drainage or unilateral adnexectomy if necessary. Laparotomy is usually reserved for patients experiencing surgical emergencies (ruptured abscesses) and patients who are not candidates for laparoscopic intervention.

Differential Diagnosis

Fitz-Hugh-Curtis Syndrome may mimic a number of other diseases. These include:

• Ectopic pregnancy
• Cholecystitis 
• Viral hepatitis
• Renal colic 
• Pyelonephritis
• Pulmonary embolism
• Appendicitis

Prognosis

There is insufficient data documenting the prognosis of FHCS as it usually responds to antibiotics very well. In one trial of triple therapy (penicillin-gentamicin-metronidazole) versus augmentin for non-chlamydial salpingitis, only one patient in each treatment group had treatment failure.[17]

Complications

One of the most common complications encountered in patients with Fitz-Hugh-Curtis syndrome is infertility.[10]

Another rarely seen complication is bowel obstruction due to adhesion formation in the peritoneal cavity.[11]

Enhancing Healthcare Team Outcomes

The diagnosis and management of HFCS are not easy and require an interprofessional team that ideally includes a gynecologist, radiologist, emergency department physician, specialty nurse, infectious disease expert, and laboratory professionals. Treatment of HFCS coincides with the management of PID. The goals of treatment are to relieve symptoms, eradicate the infection, and minimize risks of long-term sequelae (infertility or ectopic pregnancy). As the diagnosis of PID may be challenging and the potential for serious complications is great, the CDC advises that physicians maintain a low threshold for aggressive treatment. Antibiotics are successful in up to 75% of cases, and most patients with PID can be managed as outpatients. Antibiotic therapy should be geared at covering the most common organisms, C. trachomatis and N. gonorrhea, as well as gram-negative organisms, anaerobes, and streptococci.[14]

The primary care provider and nurse practitioner need to treat the partner and educate the patient on safe sex practices. It is important to follow these patients until all symptoms have subsided and the cultures are negative.