Spontaneous Splenic Rupture Caused by Scrub Typhus

Abstract

Spontaneous rupture of the spleen is rarely described as a complication of scrub typhus infection. We report a previously healthy 74-year-old Thai female farmer who presented in Nakhon Ratchasima, Thailand, with a history of fever and malaise for 5 days, followed by abdominal pain for 1 day. An exploratory laparotomy was performed due to peritonitis. Operative findings revealed a ruptured spleen and hemoperitoneum. A splenectomy was performed afterward. Scrub typhus was confirmed by a 4-fold increase of IgM titer using an indirect immunofluorescence antibody assay and a positive result from the polymerase chain reaction targeting the 47- and 56-kDa genes in Orientia tsutsugamushi. She responded well to intravenous chloramphenicol and defervesced within 24 hours without any complication.

Introduction

Scrub typhus is a rickettsial disease caused by Orientia tsutsugamushi and transmitted by chigger bite. The disease is endemic in the Asia–Pacific region.^1,2 Clinical manifestations vary from acute undifferentiated fever (AUF), with the typical presentation of fever, headache, muscle pain, eschar, and lymphadenopathy, to severe complicated disease leading to death.¹ Complications can include septic shock,³ pneumonitis,⁴ acute respiratory distress syndrome,⁵ acute renal failure,⁶ meningoencephalitis,⁷ myocarditis,⁸ disseminated intravascular coagulation,⁹ and multiorgan failure.¹ The severity of the disease depends on the strain virulence,^10,11 high copy number of O. tsutsugamushi,¹² host factors such as old age,¹³ comorbidity,¹⁴ and immunity due to prior exposure.¹⁵ We report a case of scrub typhus with a spontaneous rupture of the spleen, which is a rare complication.

Case Report

A previously healthy 74-year-old female Thai farmer came to the emergency room of Maharat Nakhon Ratchasima Hospital (MNRH), Nakhon Ratchasima, Thailand, with a history of fever, headache, and muscle pain for 5 days, followed by abdominal pain and vomiting for 1 day. On examination, she was alert, her body temperature was 39°C, blood pressure 109/93 mmHg, pulse rate of 120 beats per minute, and respiratory rate of 20 per minute. Abdominal examination showed generalized abdominal tenderness, with rebound tenderness at the right side of the abdomen. No eschar lesion was found upon complete examination of the patient's body. Laboratory results showed the following: hemoglobin 13 g/dL, leukocyte count 14,600 cell/mm³ (neutrophils 70.6%, lymphocytes 21.2%, and monocytes 8.2%), platelet count 185 × 10⁹/L, prothrombin time 16.7 seconds, international normalized ratio 1.51, activated partial thromboplastin time 42.1 seconds, thrombin time 22.3 seconds, blood urea nitrogen 8 mg/dL, and serum creatinine 0.85 mg/dL. Serum amylase, serum lipase, and urine amylase were in the normal range. Urinalysis showed specific gravity of 1.025, pH 5.5, protein 2+, blood 2+, ketone negative, red blood cells 20–30 per high-power field (HPF), and white blood cells 3–5 per HPF. Chest radiograph and abdominal film were normal. Ultrasonography demonstrated normal liver, spleen, gall bladder, pancreas, and kidneys, while a prominent size appendix was found at 7.2 mm in diameter. Computer tomography of the abdomen was not performed due to a technical problem. Electrocardiography showed sinus tachycardia with inverted T waves in V2–V4, and serial cardiac enzymes were unremarkable. Human immunodeficiency virus test was negative. The provisional diagnosis was peritonitis due to a suspected ruptured appendix, and consequently she was admitted to the surgical department. After fluid resuscitation and empirical treatment with parenteral ceftriaxone and metronidazole, a laparotomy was performed. Operative finding showed 50 mL of unclotted blood in the intra-abdominal cavity with splenic hematoma, liver and bowel congestion, and a mildly inflamed appendix. A splenectomy and appendectomy were performed. After the surgery, the patient continued to have a persistent high-grade fever, thus an infectious diseases specialist was consulted. Rickettsiosis was suspected due to acute fever without organ-specific symptoms. The commercially available SD Bioline Tsutsugamushi Assay (a rapid immunochromatographic test; Kyonggi-do, Republic of Korea) was performed at MNRH and produced a positive result indicating the presence of IgM, IgG, and IgA antibodies to O. tsutsugamushi. Intravenous chloramphenicol was prescribed for the presumed scrub typhus infection in addition to ceftriaxone while metronidazole was discontinued.

Scrub typhus was confirmed by positive polymerase chain reaction (PCR) targeting 47- and 56-kDa genes of O. tsutsugamushi in an acute serum sample. The IgM titer increased over 4-fold from 1:100 to 1:800 in paired sera taken 7 days apart using an immunofluorescent antibody assay (IFA) containing the pooled antigens of Karp, Kato, and Gilliam strains of O. tsutsugamushi. PCR targeting the lipL32, secY, and 16S rrs genes of pathogenic Leptospira species was negative; IFA for leptospirosis and murine typhus were negative. All confirmatory tests (IFA and PCR) were performed at the Infectious Diseases Laboratory of Siriraj Hospital, Mahidol University, Bangkok. Blood culture had no growth. Dengue serology and microscopic examination for malaria were negative. The patient defervesced within 24 hours after receiving intravenous chloramphenicol and was switched to doxycycline after 6 days when oral diet was resumed. She responded well to the treatment and no other complications were found. The total duration of chloramphenicol and doxycycline administration was 10 days. Pathological examination revealed splenic rupture with hematoma and periappendicitis. In the follow-up period, the patient remained well, and the O. tsutsugamushi IgG titer persisted at > 1:50 for over 12 months.

Discussion

Scrub typhus is endemic in Thailand.^16,17 The common symptoms and signs are fever, headache, muscle pain, eschar, rash, and lymphadenopathy. Although the presence of an eschar lesion is pathognomonic of scrub typhus, the incidence of eschar in adult Thai patients with scrub typhus is less than 50%.¹⁸ Gastrointestinal manifestations¹⁹ include nausea, vomiting, abdominal pain, jaundice, hepatomegaly, and splenomegaly, while complications can include gastrointestinal bleeding,¹⁹ cholecystitis,²⁰ pancreatitis,²¹ and splenic infarction.²² A ruptured spleen is a rare complication in patients with scrub typhus,²³ murine typhus,²⁴ and Mediterranean spotted fever group.²⁵ Nevertheless, splenic rupture is a known complication of various infectious diseases such as Epstein–Barr virus (infectious mononucleosis),²⁶ and malaria.²⁷ Spontaneous splenic rupture is a life-threatening condition if not recognized and appropriately managed. There is no consensus on the treatment of scrub typhus patients with spontaneous splenic rupture. Rather, it is based on the patient's hemodynamic status, splenic injury grade, comorbidities, and medical facility. Our case developed a ruptured spleen after 5 days of fever without history of abdominal trauma, and the splenectomy was performed due to hemodynamic instability.

Oral doxycycline is the treatment of choice for uncomplicated scrub typhus.¹ While both doxycycline^28,29 and chloramphenicol^1,30 have been proven to be effective in treating severe scrub typhus, symptoms such as fever dissipate slower when treated with chloramphenicol compared with tetracycline treatment.³¹ Intravenous chloramphenicol was prescribed because the hemodynamic condition of the patient was unstable, and intravenous doxycycline is unavailable in Thailand. She improved clinically after the treatment. There were only two previous case reports of splenic rupture in scrub typhus cases. Kim and others³² reported the first case of nontraumatic splenic rupture in a patient with scrub typhus in 2008, but details are not available because the article was written in Korean. In 2009, Lin and others reported a 20-year-old male Taiwanese patient with scrub typhus with intermittent fever and epigastric pain for 2 days. Spontaneous hemoperitoneum was diagnosed by abdominal non-contrast enhanced computed tomography scan and scrub typhus was confirmed by positive PCR for O. tsutsugamushi.²³ Conservative treatment and tetracycline was prescribed for 10 days. He became afebrile 24 hours later.

In conclusion, scrub typhus is a common cause of AUF in Thailand. Therefore when adult patients present with AUF and acute abdomen, the awareness that scrub typhus may be a potential causative organism would improve the likelihood of an accurate diagnosis and treatment.