Toxoplasmosis with hemophagocytic syndrome after bone marrow transplantation: diagnosis at autopsy

Abstract: Toxoplasmosis is a rare but well recognized opportunistic infection that can occur after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Besides encephalitis, other common presentations of Toxoplasma gondii infection are interstitial pneumonitis and myocarditis. Because of its non‐specific clinical and biological signs and its lethal outcome, toxoplasmosis is often misdiagnosed and only revealed at autopsy. We report a case of a postmortem diagnosis of disseminated toxoplasmosis associated with hemophagocytic syndrome, which underlines the value of necropsy in cases of death after transplantation. We also discuss clinical presentations and risk factors that lead to toxoplasmosis in allo‐HSCT recipients.     

Toxoplasmic infection in cardiac disease.

In 18 patients who presented in less than 2 years with heart disease characterized by arrhythmias (including atrial fibrillation, ventricular arrhythmias and heart block), atypical chest pain, pericarditis and cardiac failure, extensive investigation revealed no cause for the disease except for evidence of toxoplasmic infection. One patient had acute toxoplasmosis; the other 17 patients had chronically increased titers, higher than the expected level in the community and also higher than in a control series of patients with well defined heart disease. Toxoplasmosis is probably a fairly common cause of heart disease in this community. The source of infection appeared to be cats, uncooked meat and congenital infection. Patients received chemotherapy with either pyrimethamine and sulfadiazine or tetracycline. Serious relapse occurrred in three patients and embolic complications in two. Experimental myocarditis occurs when toxoplasmic cysts rupture within the heart; therefore clinical symptoms may occur sporadically during a chronic infection.     

Prevalence of toxoplasma myocarditis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE--To evaluate the prevalence of cardiac toxoplasmosis in a series of 182 necropsies performed between 1987 and 1991 on patients infected with the human immunodeficiency virus (HIV), to correlate this prevalence with the ante mortem diagnosis of cardiac involvement, and to assess the role of such cardiac lesions in the immediate cause of death. PATIENTS AND METHODS--Complete necropsies of 182 HIV-infected patients (48 women, 134 men) were performed consecutively between 1987 and 1991. Risk factors, identified in 174 cases, included drug abuse (111/182), homosexuality (51/182), and blood transfusions (12/182). 16 samples were systematically obtained from each heart for histological study. If trophozoites or lymphocytic myocarditis were seen, immunohistochemical investigations were carried out with polyclonal antibodies for Toxoplasma gondii. An ultrastructural study was performed in four patients with toxoplasma myocarditis. Myocardial lesions were defined by the Dallas classification. Clinical data (and information on electrocardiograms and echocardiograms) were obtained from medical records. RESULTS--Cardiac toxoplasmosis was diagnosed at necropsy in 21 (12%) patients. Cardiac lesions were associated with toxoplasmic encephalitis in 18 patients and were solitary in three patients. Acute diffuse myocarditis was present in 6/21, rare foci of myocarditis were seen in 8/21, and intramyocytic toxoplasmic cysts without any inflammatory reaction or necrosis were seen in 4/21. Anti-toxoplasma immunolabelling showed cardiac toxoplasmosis in three patients with lymphocytic myocarditis. Particles with the ultrastructural characteristics of Toxoplasma gondii trophozoites were seen in four cases. Six patients had presented with cardiac symptoms, confirmed by electrocardiographic and echocardiographic abnormalities during their disease course, and their cardiac lesions were directly responsible for the death. CONCLUSION--Cardiac toxoplasmosis was common in this necropsy series of HIV-infected patients. Cardiac toxoplasmosis had been suspected clinically in four patients. Myocardial lesions were generally asymptomatic and were not discovered until necropsy. Solitary cardiac involvement was not uncommon reflecting parasite reactivation at a myocardial site. The incidence of cardiac toxoplasmosis in this group of immunodepressed subjects from an area with a high prevalence of this parasitic disease justifies regular follow up of such patients by electrocardiography and echocardiography as well as immediate administration of anti-toxoplasma treatment should sudden heart failure occur.     

Toxoplasmosis-induced myocarditis

The clinical picture of myocarditis was studied in 72 patients with toxoplasmic infection and in 44 patients not suffering from this infection. Comparison of the clinical signs of myocarditis in these two groups showed that myocarditis of toxoplasmic etiology has no characteristic features. The only distinction between these two groups was the different frequency of various symptoms. In view of this, methods of laboratory diagnosis of toxoplasmosis acquire much significance.     

Acute toxoplasmic myocarditis. A cause of sudden death in a case of acquired immunodeficiency syndrome

A case of acquired immunodeficiency syndrome with a sudden death due to a toxoplasmic myocarditis is reported. The diagnosis was postmortem. At the autopsy, only the heart was affected by toxoplasmic lesions. The toxoplasmosis is a frequent disease in AIDS patients. So a toxoplasmic myocarditis must be suspected when a severe cardiac dysfunction is observed in these patients.     

Clinical criteria and evaluation of the pathology and progress of lympho-nodular toxoplasmosis

We aimed at analysis of the clinical pattern and the course of lympho-nodular toxoplasmosis taking into account the intensity and duration of the illness. Ninety seven patients (69 adults and 28 children) with lympho-nodular toxoplasmosis were examined. Toxoplasmosis was diagnosed by indirect immunofluorescence; the titres of antibodies of IgG and IgM classes were also estimated. Depending on the duration of the illness three periods: early, regression of symptoms and protraction of symptoms were defined; depending on the intensity of signs and symptoms of toxoplasmosis three courses of the disease: acute, subacute and chronic were defined. The analysis showed that clinical picture of lympho-nodular toxoplasmosis was characterized by swelling of various peripheral lymph nodes as well as by general clinical symptoms (88.7% of cases) the intensity and duration of which, to a large extent, determined course of the illness. No correlation between clinical course and duration (early and regression period) of lympho-nodular toxoplasmosis and titres IFA-IgG (before therapy) was found. Pathomorphology of lymph nodes in patients with toxoplasmic lymphadenopathy is a valuable complementary examination which renders it possible to determine the period of the disease.     

COVID-19 Myocarditis: An Emerging Clinical Conundrum

Coronavirus Disease 2019 (COVID-19) has been a significant cause of global mortality and morbidity since it was first reported in December 2019 in Wuhan, China. COVID19 like previous coronaviruses primarily affects the lungs causing pneumonia, interstitial pneumonitis, and severe acute respiratory distress syndrome (ARDS). However, there is increasing evidence linking COVID-19 to cardiovascular complications such as arrhythmias, heart failure, cardiogenic shock, fulminant myocarditis, and cardiac death. Given the novelty of this virus, there is paucity of data on some cardiovascular complications of COVID-19, specifically myocarditis. Myocarditis is an inflammatory disease of the heart muscle with a heterogenous clinical presentation and progression. It is mostly caused by viral infections and is the result of interaction of the virus and the host's immune system. There have been several case reports linking COVID-19 with myocarditis, however the true mechanism of cardiac injury remains under investigation. In this paper we review the clinical presentation, proposed pathophysiology, differential diagnoses and management of myocarditis in COVID-19 patients.     

Disseminated Toxoplasmosis in a Patient with Non-Hodgkin Lymphoma

Toxoplasmosis is a well-recognized opportunistic disease in HIV-infected individuals that is caused by the reactivation of a previous infection, primarily in the central nervous system, during profound immunodeficiency. Toxoplasmosis has been described more rarely in patients with cancer and chemotherapy. We report a case of a patient with a history of chemotherapy for non-Hodgkin lymphoma who developed pain and progressive paresthesia of the right arm 6 weeks after remission. Relapsing lymphoma was suspected, and steroid and radiation treatment were initiated, but the patient died 5 days later due to multiple organ failure. Autopsy revealed disseminated toxoplasmosis. This case illustrates that toxoplasmosis should be suspected in patients with neoplastic disease, especially lymphomas, who present with unexplained neurologic, pulmonary, or febrile symptoms during or after chemotherapy.     

Clinical spectrum in 107 cases of toxoplasmic lymphadenopathy

Lymphadenopathy is the most frequent clinical manifestation of acute acquired infection with Toxoplasma in the immunocompetent individual. One hundred seven cases of histologically verified toxoplasmic lymphadenitis were reviewed in an effort to determine the usual modes of clinical presentation and the incidence of extranodal disease. Toxoplasmic lymphadenitis most frequently involved a solitary lymph node in the head and neck regions, without systemic symptoms or extranodal disease and with a benign clinical course. However, serious extranodal disease did occur in some patients and included myocarditis, pneumonitis, encephalitis, chorioretinitis, and transmission of the infection to the fetus. Case histories are presented to illustrate important points with respect to clinical presentation, complications, and diagnosis.     

Cutaneous manifestations of toxoplasmosis.

Toxoplasmosis is a common, largely asymptomatic infection. Early reports of acquired disease noted frequent dermatologic manifestations, whereas recent reviews of toxoplasmosis stress the lymphadenopathic presentation of the disease. We report the case of a patient with acute toxoplasmosis associated with a prominent macular and papular rash involving the palms and soles. We have reviewed the literature on dermatologic manifestations of acute acquired toxoplasmosis to underscore the importance of considering toxoplasmosis in the differential diagnosis of febrile illnesses with varied dermatologic presentations.     

Toxoplasmosis, a severe complication in allogeneic hematopoietic stem cell transplantation: successful treatment strategies during a 5-year single-center experience.

Toxoplasmosis is a rare but often fatal complication that occurs after patients undergo allogeneic hematopoietic stem cell transplant. At our institution, toxoplasmosis was diagnosed in 8 of 301 patients who received stem cell transplants. Disseminated toxoplasmosis with a rapid fatal course was observed in 2 patients. Six patients had cerebral toxoplasmosis diagnosed on the basis of neurological signs and observation of the patients' mental confusion, seizures, and typical lesions (which were assessed by computed tomography, magnetic resonance imaging, or both). Seroconversion of antitoxoplasma immunoglobulin and a discovery of toxoplasma deoxyribonucleic acid in the cerebrospinal fluid (confirmed by use of polymerase chain reaction) were documented in all patients. Treatment consisted of clindamycin therapy (for 2 patients) and of pyrimethamine-clindamycin therapy, sulfadiazine therapy, or both (for 5 patients). Patients showed improvement after therapy, as assessed by clinical and radiological means. Three of 8 patients survive-1 without any residual neurological symptoms and 2 with minimal neurological symptoms.     

The role of toxoplasmosis in congenital disease in Malaysia

Toxoplasmosis was found not to be an important cause of intrauterine infection in Malaysia as the rate of toxoplasma-specific IgM in 1,060 congenitally defective Malaysian children, 0 to 4 months old (0.4%) was lower than that in 405 normal children of the same age group (2.0%). A total of 8.2 intra-uterine toxoplasmic infections per 1,000 live births was detected of which one-third (2.7 per 1,000 live births) was overt, manifesting symptoms more of liver damage, than eye or brain damage. A comparison was made with the rates in U.S.A. and Europe. The role of toxoplasmosis in abortion needs to be studied.     

Disseminated toxoplasmosis presenting as symptomatic orchitis and nephrotic syndrome

Toxoplasma gondii is a common pathogen in patients with acquired immune deficiency syndrome (AIDS). The most common modes of presentation are related to the central nervous system (CNS), usually with headache, fever, and focal neurological signs. Extra-neural manifestations are unusual in patients with AIDS. The authors present a patient with AIDS who had disseminated toxoplasmosis whose initial clinical presentation was symptomatic orchitis and the nephrotic syndrome (NS). Testicular involvement with toxoplasmosis has been described only rarely, predominantly as an incidental finding at autopsy. Toxoplasmosis is a rare cause of nephrotic syndrome, with the majority of cases associated with congenital infection. In this case, the nephrotic syndrome remitted only after orchiectomy and chemotherapy for toxoplasmosis, but recurred when the patient had a relapse of his CNS disease. Toxoplasmosis in AIDS may present with extra-neural manifestations and may be an etiologic agent for NS in some patients with AIDS.     

Fulminant and fatal encephalitis caused by Acanthamoeba in a kidney transplant recipient: case report and literature review

Acanthamoeba is the most common cause of granulomatous amebic encephalitis, a typically fatal condition that is classically described as indolent and slowly progressive. We report a case of Acanthamoeba encephalitis in a kidney transplant recipient that progressed to death within 3 days of symptom onset and was diagnosed at autopsy. We also review clinical characteristics, treatments, and outcomes of all published cases of Acanthamoeba encephalitis in solid organ transplant (SOT) recipients. Ten cases were identified, and the infection was fatal in 9 of these cases. In 6 patients, Acanthamoeba presented in a fulminant manner and death occurred within 2 weeks after the onset of neurologic symptoms. These acute presentations are likely related to immunodeficiencies associated with solid organ transplantation that result in an inability to control Acanthamoeba proliferation. Skin lesions may predate neurologic involvement and provide an opportunity for early diagnosis and treatment. Acanthamoeba is an under‐recognized cause of encephalitis in SOT recipients and often presents in a fulminant manner in this population. Increased awareness of this disease and its clinical manifestations is essential to attain an early diagnosis and provide the best chance of cure.     

Acute exacerbation of Toxoplasma gondii infection after hematopoietic stem cell transplantation: five case reports among 279 recipients

Toxoplasmosis is a rare and possibly underestimated complication following hematopoietic stem cell transplantation (HSCT) associated with a high mortality rate, although the incidence of toxoplasmosis after HSCT in Japan has not been established. We retrospectively studied patients with toxoplasmosis after HSCT, and identified five patients who had been diagnosed with an acute exacerbation of toxoplasmosis among 279 HSCT recipients at our institution between 1998 and 2011, representing an incidence of 1.8 %. Among 87 autologous HSCT recipients, one definite case was diagnosed. The serological test for Toxoplasma gondii before HSCT was positive in 18 of 192 allogeneic HSCT recipients. Of the 18 seropositive patients, three had definite infections, and one had possible infection. All four definite cases were diagnosed at autopsy. In the definite cases, three allogeneic HSCT recipients had disseminated or pulmonary toxoplasmosis and one autologous HSCT recipient had toxoplasmic encephalitis, although toxoplasmosis was not suspected at the premortem examination due to non-specific clinical and radiological manifestations. Thus, acute exacerbation of toxoplasmosis should be suspected in recipients after HSCT. Early diagnosis and treatment for toxoplasmosis would certainly contribute to a decrease in mortality after HSCT.     

Successful treatment of toxoplasmic encephalitis diagnosed early by polymerase chain reaction after allogeneic hematopoietic stem cell transplantation: two case reports and review of the literature

Toxoplasmic encephalitis represents a rare, but often fatal infection after allogeneic hematopoietic stem cell transplantation. Polymerase chain reaction (PCR)‐based preemptive therapy is considered promising for this disease, but is not routinely applied, especially in low seroprevalence countries including Japan. We encountered 2 cases of toxoplasmic encephalitis after transplantation that were successfully treated. The diagnosis of toxoplasmic encephalitis in these cases was confirmed by PCR testing when neurological symptoms were observed. Both patients received pyrimethamine and sulfadiazine treatments within 2 weeks of the development of neurological symptoms, and remained free of recurrence for 32 and 12 months. These results emphasized the importance of the PCR test and immediate treatment after diagnosis for the management of toxoplasmic encephalitis.     

Congenital toxoplasmosis from an HIV-infected woman as a result of reactivation

Congenital toxoplasmosis usually results from acquired infection in non-immune pregnant women. However, severely HIV-infected women with a latent Toxoplasma infection can transmit the parasite as a result of reactivation. We report a case of toxoplasmic reactivation in an HIV-infected woman with moderate immunosuppression resulting in a severe congenital toxoplasmosis.     

Disseminated toxoplasmosis: an atypical presentation in an immunocompetent patient

Acute acquired toxoplasmosis is considered a self-limited mononucleosis-like disease that rarely requires treatment. We report an unusual severe case of disseminated toxoplasmosis complicated with meningitis and pneumonia in a previously 41-year-old healthy Brazilian man. Toxoplasmosis should be included in the differential diagnosis of acute febrile diseases due to the non-specific clinical symptoms and the possibility of severe outcome.     

Massive Cerebral Edema Associated with Fulminant Hepatic Failure in Acetaminophen Overdose

Cerebral edema may complicate the course of fulminant hepatic failure. Response to conventional therapy has been disappointing. We present a patient with fatal acetaminophen-induced fulminant hepatic failure, with signs and symptoms of cerebral edema, unresponsive to conventional medical therapy. Cranial decompression was carried out. A justification of the need for further evaluation of cranial decompression in such patients is presented.     

Toxoplasma gondii pneumonitis in patients infected with the human immunodeficiency virus.

Pulmonary toxoplasmosis is a rarely recognized opportunistic infection in immunocompromised patients. A few case reports have described pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in association with Toxoplasma gondii central nervous system disease. We encountered six cases of pulmonary toxoplasmosis in human immunodeficiency virus-infected patients who presented with a protracted febrile illness, respiratory symptoms, and an abnormal chest roentgenogram in the absence of neurologic findings. No clinical or roentgenographic features distinguished T gondii pneumonitis from more common opportunistic pulmonary infections. As the acquired immunodeficiency syndrome epidemic progresses, the presenting illnesses have evolved. Toxoplasma gondii must be considered a potential cause of pulmonary disease during the evaluation of human immunodeficiency virus-infected patients with respiratory symptoms.