Primary Toxoplasma gondii infection-associated with hemophagocytic syndrome in a man with HIV infection: a case report

Background Reactivation of latent Toxoplasma gondii (T. gondii) infection is more common than primary infection in patients with human immunodeficiency virus (HIV). We report a rare case of primary T. gondii infection-associated hemophagocytic syndrome (HPS). Case presentation A man with HIV infection presented with fever, dyspnea and pancytopenia. He was diagnosed with primary T. gondii infection by the seroconversion from single-positive IgM antibody to double-positive IgM and IgG antibody. Metagenomic next-generation sequencing (mNGS) of a plasma sample yielded high reads of T. gondii DNA. He responded well to combined anti-Toxoplasma medicines and glucocorticoid treatment. Conclusions In patients with HPS and positive T. gondii IgM antibody, mNGS analysis of a peripheral blood sample is helpful in diagnosing disseminated T. gondii infection. The dynamic changes by serological detection for IgM and IgG of T. gondii further supported the inference that the patient has experienced a primary T. gondii infection.

Usefulness of the modified hemophagocytic syndrome diagnostic score as a prognostic factor in lung transplantation patients

Background: Lung transplantation (LTX) is an established treatment for end-stage lung disease; however, the post-LTX mortality rate remains high. This study aimed to evaluate the prognostic value of the modified reactive hemophagocytic syndrome diagnostic score (mHScore) and its individual components on mortality after LTX.Methods: We retrospectively analyzed 294 patients who underwent LTX at Severance Hospital, Yonsei University, Korea, from January 2012 and December 2020, and classified them into high (n=114, mHScore > 104.0) and low mHScore (n=180, mHScore ≤ 104.0) groups. Triglyceride, ferritin, serum glutamic oxaloacetic transaminase, fibrinogen, and cytopenia were used to calculate the mHScore. We compared baseline characteristics and mortality rates as LTX prognostic factors.Results: The high mHScore group had significantly more cytopenia and higher ferritin, triglyceride, lactate dehydrogenase, and C-reactive protein levels than the low mHScore group. The mortality rate was significantly higher in the high than in the low mHScore group (hazard ratio, 4.429, p < 0.001). Multivariate regression analysis revealed that a high mHScore was significantly associated with postoperative mortality, even after adjusting for other confounding factors. A high mHScore was also associated with postoperative complications.Conclusions: The mHScore can be used to estimate post-LTX prognosis and predict postoperative mortality.

T-cell lymphoma-associated hemophagocytic syndrome in an American Pit Bull Terrier

A 3-y-old, intact female, American Pit Bull Terrier was presented because of acute onset of anorexia and a large subcutaneous submandibular mass that had been present for 3 wk. The submandibular mass, 2 engorged black-legged ticks on the dorsum of the neck, pyrexia, and icterus were seen on physical examination. Abnormal laboratory test results included a positive Anaplasma antibody test, severe thrombocytopenia, mild nonregenerative anemia, hyperbilirubinemia, and elevated liver enzyme activities. Cytology of the mass was interpreted as marked septic purulent inflammation with acute hemorrhage. Treatment with doxycycline for anaplasmosis was unsuccessful, and the patient died at an emergency follow-up visit 2 d after the initial presentation. Autopsy and histopathology revealed widespread metastasis of a presumptive histiocytic neoplasm with associated hemophagocytosis seen in lymph nodes (LNs), liver, and spleen. Immunohistochemistry yielded a definitive diagnosis of a CD3+/CD18+ T-cell lymphoma. In this case of canine lymphoma-associated hemophagocytic syndrome, hemophagocytes were observed as >2% of neoplastic cells in the liver, spleen, and LN histologically, a scarce or unreported finding, to our knowledge. The prognosis was grave, with a short survival time after the onset of clinical signs.

Gestational Psittacosis With Secondary Hemophagocytic Syndrome: A Case Report and Literature Review

Gestational psittacosis and hemophagocytic syndrome (HPS) are rare clinical diseases. In this article, a case of gestational psittacosis concomitant with secondary HPS was reported. An analysis was performed on the clinical characteristics, signs, laboratory findings, progression, diagnosis, and treatment of a patient with gestational psittacosis concomitant with secondary HPS. Besides, the literature with respect to this disease was reviewed. This patient was definitively diagnosed through metagenomic next-generation sequencing techniques, bone marrow puncture and smear examination, and the determination of sCD25 level and natural killer (NK) cell activity. Anti-infectives such as doxycycline and etoposide combined with hormone chemotherapy achieved significant improvement in cough and expectoration, a return to normal temperature, and a significant improvement in oxygenation index. In addition, chest computed tomography revealed obvious absorption of lung lesions and a return of NK cell activity and sCD25 levels to normal ranges. Chlamydia psittaci pneumonia requires a clear determination of etiology, while HPS requires bone marrow puncture and smear examination, together with the determination of sCD25 level and NK cell activity in the blood. The findings of this study suggest that metagenomic next-generation sequencing is an effective instrument in clearly identifying pathogens that cause lung infection. Clinicians should consider atypical pathogens of lung infection in patients with poor response to empirical anti-infectives, and strive to design an effective treatment strategy as per an accurate diagnosis based on the etiology. As for patients suffering from long-term high fever and poor temperature control after broad-spectrum antibiotic treatment, non-infectious fever should be taken into account. A rapid and clear diagnosis would significantly improve patient prognosis.

Case Report: Use of Liposomal Amphotericin B in Low Doses in Patients With Visceral Leishmaniasis

Background: No consensus has been reached regarding the optimal therapy for visceral leishmaniasis (VL), which affects ~12 million people worldwide.Case Presentation: This report described four cases of VL encountered in the First Affiliated Hospital of Xi'an Jiaotong University between October 2019 and December 2020. Of the four patients, one patient experienced relapse after antimonial treatment, and the remaining patients had primary VL (including one patient with impaired kidney function and one patient with hemophagocytic syndrome). All patients received a novel treatment protocol, namely the low-dose L-AmB therapy, which was characterized by a low initial dose, cautious dose escalation, and low-dose therapy as maintenance. All patients were cured without severe complications, and there was no further recurrence during follow-up.Conclusions: This case series demonstrated the safety and efficacy of the low-dose L-AmB therapy for VL patients, providing novel treatment protocol for the VL.

High-Dose Intravenous Acyclovir Is Safe and Effective in the Treatment of EBV Reactivation Post Allogeneic Hematopoietic Stem Cell Transplantation

Backgroud: Reactivation of nasopharyngeal carcinoma virus (EBV) post allogeneic hematopoietic stem cell transplantation(allo-HSCT) is very common, but sustained EBV activation maybe induce EBV-associated lymphoproliferative disease (PTLD), transplant-associated hemophagocytic syndrome and thrombocytopenia after transplantation, which is extremely harmful for long-term survival. Currently, the first-line therapeutic strategy for sustained EBV activation is rituximab, but rituximab leads to increased rates of infections and delayed immune reconstitution. Therefore, for the patients with EBV-DNA copies under 1000000/mL, the pros and cons of rituximab are worth weighing. Objective: To evaluate the efficacy and safety of high-dose intravenous acyclovir in the treatment of EBV reactivation post allo-HSCT. Method: Retrospective analysis of clinical data of patients with EBV reactivation post transplantation treated with high-dose intravenous acyclovir (0.5g Q8H) in Sichuan Provincial People's Hospital from January 2019 to May 2021. A total of 49 patients post allo-HSCT from from January 2019 to May 2021 were enrolled in this study. In this population, 38 patients accepted haplo-SCT and 11 patients accepted sibling-SCT. These patients all don't suffer from PTLD and transplant-associated hemophagocytic syndrome, but are resistant to oral antiviral drugs (Acyclovir, valacyclovir, and famciclovir). Simultaneously with intravenous acyclovir, all patients received human immunoglobulin with one dose of 0.4g/kg. The clinical efficacy was evaluated as follows: Overall response(ORR) was defined as the decrease of EBV copies; Complete remission(CR) was defined as the negative turn of EBV copies; Partial response(PR), Stable disease(SD) and Progression of disease(PD) were respectively defined as the decrease, no significant change and increase of EBV copies. Results: The median transplantation time was +86 (+38 to +1587) days. The median number of EBV-DNA copies/ml was 177000 (6620-8200000). After treatment with high-dose intravenous acyclovir, 29 (59.2%) of 49 patients achieved CR, 10 (20.4%) of 49 patients achieved PR, and 10 (20.4%) of 49 patients had no response, including 2 patients with SD and 8 patients with PD. All 49 patients had responded to this regimen with 79.6% ORR. The median time of response and negative turn was 4 days (2 to 11 days) and 9 days (2 to 23 days) respectively. After 100 days for follow-up, 14 of 39 responding patients suffered from EBV activation again, and the EBV copies were higher than that when high-dose acyclovir was initiated. All 24 patients who did not turn negative were recommended with the treatment of rituximab, and 19 of 20 patients who completed treatment turned negative during the three months post acyclovir treatment. The main adverse events (AEs) of this regimen were neutropenia (CTCAE grade 2-3, 8 in 49 patients), thrombocytopenia (CTCAE grade 2-3, 10 in 49 patients), increased serum creatinine (CTCAE grade 1-2, 4 in 49 patients), phlebitis (6 in 49 patients). These AEs were all reversible, which recovered after withdrawal. There was no significant change in the counts of CD4 + T cells and CD8 + T cells before and after intravenous high-dose acyclovir. Conclusion: High-dose intravenous acyclovir is safe and effective in the treatment of EBV reactivation post allo-HSCT, although nearly half of patients still need rituximab treatment. It is a reasonable strategy for patients with oral antiviral resistance. Most patients can avoid the prescription of rituximab in the first six months post allo-HSCT, without interference of immune reconstitution. Disclosures No relevant conflicts of interest to declare.

Subcutaneous panniculitis-like T cell lymphoma: a rare entity and its cryptic journey through pregnancy

<p class="abstract">Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of skin lymphoma that primarily is localized to the subcutaneous adipose tissue and accounts for less than 1% of all peripheral T-cell lymphomas. It presents with multiple subcutaneous nodules or plaques on extremities and has poor prognosis if accompanied by hemophagocytic syndrome. Differential diagnosis is panniculitis, lupus panniculitis and leprosy. We report such a rare case of a female with lupus erythematosus (LE) panniculitis like presentation with favourable outcome to oral steroids in pregnancy.</p>

Diagnostic Value of Bone Marrow Cell Morphology in Visceral Leishmaniasis-Associated Hemophagocytic Syndrome of Two Cases

Background: Visceral leishmaniasis related-hemophagocytic lymphohistiocytosis (VL-HLH) is a hemophagocytic syndrome caused by Leishmania infection. VL-HLH is rare, especially in nonendemic areas where the disease is severe, and mortality rates are high. The key to diagnosing VL-HLH is to find the pathogen; therefore, the Leishmania must be accurately identified for timely clinical treatment.Case presentationWe retrospectively analyzed the clinical data, laboratory examination results and bone marrow cell morphology of two children with VL-HLH diagnosed via bone marrow cell morphology between July 2017 and January 2021 at Kunming Children’s Hospital of Yunnan, China.Two cases suspected of having malignant tumors at other hospitals and who had undergone ineffective long-term treatment were transferred to Kunming Children’s Hospital. They had repeated fevers, pancytopenia, hepatosplenomegaly, hypertriglyceridemia, and hypofibrinogenemia over a long period and met the HLH-2004 standard. Their HLH genetic test results were negative, and primary HLH was excluded. Both children underwent chemotherapy as per the HLH-2004 chemotherapy regimen , but it was ineffective and accompanied by serious infections. We found Leishmania amastigotes in their bone marrow via morphological examination of their bone marrow cells, which showed hemophagocytic cells; thus, the children were diagnosed with VL-HLH. After being transferred to a specialty hospital for treatment, the condition was well-controlled. Conclusion: Morphological examination of the bone marrow cells played an important role in diagnosing VL-HLH. When clinically diagnosing secondary HLH, VL-HLH should be considered in addition to common pathogens, especially in patients for whom HLH-2004 chemotherapy regimens are ineffective. For infants and young children, bone marrow cytology examinations should be performed several times and as early as possible to find the pathogens to reduce potential misdiagnoses.

A case of Castleman disease with hemophagocytic syndrome derived from HHV8 infection

Background For a patient presenting with fever, multiple lymphadenopathy and splenomegaly, pathogen infection should be preferentially considered, followed by lymphoid malignancies. When traditional laboratory and pathological detection cannot find the pathogenic microorganism, metagenomic sequencing (MGS) which targets the person’s genome for exceptional genetic disorders may detect a rare pathogen. Case presentation Here, we introduced the diagnostic clue of a case of multicentric Castleman disease (MCD) with hemophagocytic syndrome which was elicited from the detection of human herpesvirus-8 in the blood of a HIV-1 infected person by MGS technology during pathogen inspection. This case highlights the need to increase the awareness of MCD among clinicians and pathologists. Conclusions MGS technology may play a pivotal role in providing diagnostic clues during pathogen inspection, especially when pathogens are not detectable by conventional methods.

Clinical Features of Severe Tsutsugamushi Disease Complicated with Hemophagocytic Lymphohistiocytosis

The article discusses a case of severe tsutsugamushi disease complicated with hemophagocytic syndrome in Guangdong Maternal and Child Health Hospital and concludes that blood purification technology has significant therapeutic effect among children with severe HLH complicated with multiple organ dysfunction.