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Acute acalculous cholecystitis in an
immunocompetent patient with severe
acquired toxoplasmosis

Colecistitis aguda acalculosa en un paciente inmunocompetente
con toxoplasmosis severa adquirida
Jaime R. Torres1
Lérida Padrón2
Hipólito García B3


1Internal Medicine, Infecology, Tropical Medicine Institute, Universidad Central de Venezuela, Caracas, Venezuela.
2Internal Medicine, Neumonology, Department of Medicine, Clínica Santa Sofía, Caracas, Venezuela.
3Internal Medicine, Critical Care, Adults Intensive Care Unit, Clínica Santa Sofía, Caracas, Venezuela.


Conflicto de intereses: ninguno


Rev Panam Infectol 2006;8(1):45-47


Recibido el 5/12/2005.
Aceptado para publicación el 9/3/2006.		 Abstract
Acute acalculous cholecystitis (AAC) is an inflammatory disease of the gallbladder not associated with gallstones. It is more often seen in hospitalized patients on mechanical ventilation due to life-threatening conditions and superimposed sepsis. Occasionally, infection itself may be the only predisposing factor identified. AAC has rarely been observed in severely immunocompromised patients with reactivated Toxoplasma infection. We were able to document for the first time a case of AAC in an otherwise healthy adult with acute acquired toxoplasmosis. A prompt diagnosis and early onset of effective antiparasitic treatment allowed the resolution of the episode without further complication.
Key words: Acute, acalculous, cholecystitis, acquired toxoplasmosis.


Resumen
La colecistitis aguda acalculosa (CAA) es una enfermedad inflamatoria de la vesícula biliar no asociada con litiasis. Es observada más frecuentemente en pacientes hospitalizados sometidos a ventilación mecánica debido a condiciones clínicas graves complicadas con sepsis secundaria. Ocasionalmente, la infección misma puede ser el único factor predisponente identificado. La CAA ha sido observada raramente en pacientes severamente inmunocomprometidos con toxoplasmosis reactivada. Recientemente, tuvimos la oportunidad de documentar por primera vez un caso de CAA en una paciente adulta previamente sana con una toxoplasmosis aguda adquirida. La realización de un diagnóstico etiológico precoz y la rápida instauración de un tratamiento antiparasitario efectivo, permitió la resolución del proceso en forma satisfactoria.
Palabras clave: Toxoplasmosis, aguda, adquirida, colecistitis acalculosa


Introduction
Acute acalculous cholecystitis (AAC) represents inflammation of the gallbladder in the absence of demonstrated calculi. Usually, it occurs as a secondary event in patients who are hospitalized and acutely ill from another cause(1,2). AAC may also associate with vascular disease and immune deficiency(1-3). This condition causes approximately 5-10% of all cases of acute cholecystitis and, depending on the underlying illness, may associate with more serious morbidity and higher mortality rates than calculous cholecystitis(1-4).

Critically ill patients, especially those with increased bile viscosity due to fever and dehydration, or prolonged absence of oral feeding, are more predisposed to AAC as a consequence of decreased cholecystokinin-induced gallbladder contraction. Gallbladder wall ischemia that occurs because of a low-flow state may also play a role in the pathogenesis of AAC(1,4).

Seldom, infection may be the primary predisposing event of AAC, as reported with Salmonella (typhoid fever), Staphylococcus, Brucella, dengue virus, Leptos­pira, and in AIDS-related infection by cytomegalovirus and Cryptosporidium(4-9). Some of these agents, or their antigens, may be found within the gallbladder mucosa, around blood vessels of the serosa and/or in the muscle layers, suggesting that the local inflammatory changes observed are due to actual invasion(4-8).

Whereas AAC has occasionally complicated Toxoplasma infection in severely immunocompromised patients, we are not aware of any prior report in an immunocompetent host. We here in comment on our recent experience with one such patient who developed AAC in the course of a severe acute acquired toxoplasmosis.

Case report
A 44 year-old, white, previously healthy Venezuelan female veterinarian, experienced persistent hyperthermia, chills, hyporexia, asthenia, generalized headache, non-inflammatory diarrhea, and persistent diffused abdominal pain, for seven days. On admission, a maculo-papular rash involving trunk and lower limbs, and multiple small non-tender adenomegalies, were noticed. Pain was elicited on palpation of right hypochondrium and epigastrium. Clinical laboratory results were unremarkable except for mild thrombocytopenia of 110.000 x mm3, reactive Protein C levels of 12.8 g/dL, ALT 184 U/L, ALP 299 IU/L, total bilirubin 2.3 mg/dL and serum LDH levels of 440 IU/L. Diagnostic samples were collected for stool, urine and blood cultures, as well as for HIV, CMV, EBV, Leptospira, Brucella, and dengue serology, all of which were turned out negative.

Results of a commercial ELISA test for Toxoplasma gondi (PlateliaToxo IgM®, Bio-Rad Laboratories Diagnostic Group, Redmond, Wash., USA) revealed a significant serum level of specific IgM. Acute blood samples taken on day 5th of clinical illness were strongly positive by means of an in-house polymerase chain reaction (PCR) assay targeting the repetitive 35-copy-number B1 gene of Toxoplasma (Laboratorio Genomik, Maracay, Aragua, Venezuela).

Over the next 48 hours the patient developed severe nausea, and increased abdominal pain focalized on the right hypochondrium and epigastrium, with a positive Murphy’s sign. An abdominal ultrasound revealed mode­rate hepatosplenomegaly and an enlarged gallbladder with thickened wall (>10 mm), and pericholecystic fluid. These findings were corroborated by CT scanning (see figure 1).



Due to a recent history of hypersensitivity to sulfonamides, antiparasitic treatment with azytromicin 500 mg VO, BID plus pyrimethamine, at a loading dose of 75 mg PO and then 50 mg PO every 24 hours, for 21 days, was initiated. The patient steadily recovered, becoming asymptomatic after 7 days, when she was discharged.


Discussion
The diagnosis of AAC requires a high degree of suspicion on the part of the physician, since the sensitivity and specificity of both clinical and imaging evaluation are often decreased because of comorbidities. Besides, many infectious or inflammatory processes may result in nonspecific findings(1-4,10).

As seen in the current case, the most frequent physical and laboratory findings in AAC include fever, right upper quadrant pain, nausea, leukocytosis, and elevation of liver-associated enzymes and bilirubin(1-4). Early imaging evaluation is required, and frequently, multiple diagnostic tests need to be performed. Imaging modalities often are complementary, with ultrasound (US) or CT providing anatomic information and evaluation of adjacent structures and cholescintigraphy providing functional information(1-4,10).

AAC has been recognized in at least one immunocompromised patient who experienced reactivation of a chronic latent Toxoplasma infection after allogeneic stem cell transplantation, and in another patient with advanced HIV infection complicated with ascites and gallbladder perforation(5,11). Both cases were documented pos-mortem. Poor prognosis is probably linked to a difficult diagnosis, based mainly on the detection of parasites in tissue. Serological tests are of little help in these cases and, when positive, they only indicate that the patient is at risk of reactivation as they harbour Toxoplasma cysts. In this context, a positive PCR result with blood allows the onset of specific antiparasitic treatment even when the parasite burden is still low(11).

Information is lacking on the pathological and clinical implications of this unusual condition. It is conceivable that the parasite could invade the gallbladder wall cau­sing inflammatory changes which instead would result in functional obstruction of the cystic duct. Histological examination of surgically obtained specimens in similar patients would help to clarify this contention. Invasive procedures aimed to collect diagnostic histological material in this case were pondered, but considered unjustified, in view of the patient’s rapid recovery after onset of effective anti-parasitic treatment.

Azythromycin alone or in combination with pyrimethamine, has proven effective both in vivo and in vitro for the treatment of Toxoplasma infection(12-14). This combination is often used as a convenient alternative when the patient is allergic or intolerant to sulphadiazine.

Whereas some bacterial agents potentially associated with primary AAC, such as Salmonella (both S. typhi and Salmonella spp.), Staphylococcus, Brucella, and Leptospira(4,6-8), might as well have been inhibited by azythromycin, all of them were excluded in the current case by the detailed laboratorial workup carried out, which included stool, urine and blood cultures, serology for Leptospira, Salmonella and Brucella, and a PCR determination for Leptospira.

Complications of AAC are much higher than in the calculous variety of the disease because of the variable pathophysiology, comorbid conditions, and the frequent delay in diagnosis and treatment. Perforation or gangrene may occur in more than 50% of patients. Gangrene can be either diffuse or focal and frequently is associated with perforation. The outcome of patients with AAC depends to a large extent on their underlying illness, but lethality can be as high as 30-60% when perforation of the gallbladder occurs.

Although the AAC in this patient resolved without further complication, probably as a result of early diagnosis and effective treatment, it did entail a more protracted hospital course(1-4).


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Corresponding:
Dr. Jaime R. Torres
Avenida Principal de Santa Sofía, Edificio Alfa,
Oficina 2-D, El Cafetal, Caracas 1080, Venezuela.
e-mail address: torresj@post.com