Case report: The devil was hidden in the mastocytes - an unusually fulminant case of indolent systemic mastocytosis in a 45-year-old patient, missed for almost 20 years.

Indolent systemic mastocytosis (ISM) represents the most common form of SM, typically following a slow clinical course. While anaphylactic reactions may come up in the life course of an ISM patient, these are often moderate and do not pose a threat to patient's health. Here, we present an undiagnosed case of ISM with recurrent severe anaphylactic episodes following consumption of food and emotional stress. One of these episodes led to anaphylactic shock, necessitating temporary mechanical ventilation and intensive care unit (ICU) support. Besides hypotension, a diffuse, itchy, red rash was the only notable clinical finding. Upon recovery, we found abnormally high baseline serum tryptase level as well as 10% bone marrow (BM) infiltration by multifocal, dense clusters of CD117+/mast cell tryptase+/CD25+ mast cells (MCs), consolidating the diagnosis of ISM. Prophylactic treatment with a histamine receptor antagonist was initiated, resulting in milder episodes thereafter. Diagnosis of ISM requires a high level of suspicion; its prompt recognition and treatment are important in preventing potentially life-threatening anaphylactic episodes.

Treatment with 3-day methylprednisolone pulses in severe cases of COVID-19 compared with the standard regimen protocol of dexamethasone.

Since the outbreak of COVID-19, research has been focused on establishing effective treatments, especially for patients with severe pneumonia and hyperinflammation. The role and dose of corticosteroids remain obscure. We evaluated 58 patients with severe COVID-19 during two periods. 24 patients who received methylprednisolone pulses (250 mg/day intravenously for 3 days) were compared with 34 patients treated according to the standard dexamethasone protocol of 6 mg/day. Among non-intubated patients, the duration of hospitalization was shorter for those who received methylprednisolone pulses (9.5 vs 13.5, p<0.001). In a subgroup analysis of patients who required intubation, those treated with the dexamethasone protocol demonstrated a relative risk=1.89 (p=0.09) for dying, in contrast to the other group which showed a tendency towards extubation and discharge from the hospital. A 'delayed' need for intubation was also observed (6 vs 2 days, p=0.06). Treatment with methylprednisolone pulses significantly reduced hospitalization time. Although there was no statistically significant influence on the necessity for intubation, methylprednisolone pulses revealed a tendency to delay intubation and hospital discharges. This treatment could benefit patients in the hyperinflammatory phase of the disease.

Syphilis infection in an HIV patient presenting with leukemoid reaction: Case report and review of the literature.

Leukemoid reaction (LR) is an uncommon though dreadful sign for the treating physician, as it is related to increased mortality. In the few series that have addressed its incidence and clinical significance, infectious causes count for about half of the cases of LR, the rest accounting for cancer, drugs or rarer causes. In the HIV setting, it represents an even rarer event, owing probably to the impaired granulocytic response of AIDS patients to bacterial agents. However no report exists as to the incidence of LR to the immune-restored HIV patients adequately treated with antiretroviral therapy (ART). Syphilis is a well known cause of mild lymphocytosis, though only one report of LR exists in the congenital setting. We hereby report a case of an HIV patient adequately treated with ART, who presented with LR with a lymphomonocytic preponderance after infection with treponema pallidum.

Successful Treatment of immune Reconstitution Inflammatory syndrome-related Hemophagocytic Syndrome in an HIV Patient with Primary Effusion Lymphoma.

Although the connection of [secondary hemophagocytic syndrome (sHS)] with HIV has been well documented, optimal treatment regimen is not well established. This is due not only to the rarity of the syndrome, but also to the heterogeneity of the involved population. Most cases are related to opportunistic infections or malignancies in advanced stage, but many cases are also related to seroconversion, in the primary infection setting. Moreover, in the [antiretroviral treatment (ART)] era, rare cases of ART-related sHS have been reported. In these, often fatal cases, an [immune reconstitution inflammatory syndrome (IRIS)] process is involved, posing a serious challenge to the treating physician. We hereby report a case of successful treatment of an HIV patient with primary effusion lymphoma who experienced sHS shortly after ART onset. Our patient, treated with high dose dexamethasone and gamma globulin, achieved complete remission. This case might hint possible therapeutic insights in the treatment of IRIS-related sHS.

In vitro anti-inflammatory and anti-coagulant effects of antibiotics towards Platelet Activating Factor and thrombin.

BACKGROUND: Sepsis is characterized as a systemic inflammatory response that results from the inability of the immune system to limit bacterial spread during an ongoing infection. In this condition the significant mediator of inflammation Platelet Activating Factor (PAF) and the coagulant factor thrombin are implicated. In animal models, treatment with PAF-antagonists or co-administration of antibiotics with recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited promising results. In order to examine the putative anti-inflammatory and/or antithrombotic interactions between antibiotic treatment used in sepsis with PAF and/or thrombin, we studied the in vitro effects of these compounds towards PAF or/and thrombin related activities and towards PAF basic metabolic enzymes. METHODS: We assessed the inhibitory effect of these drugs against PAF or thrombin induced aggregation on washed rabbit platelets (WRPs) or rabbit Platelet Reach Plasma (rPRP) by evaluating their IC50 values. We also studied their effect on Cholinephosphotransferase of PAF (PAF-CPT)/Lyso-PAF-Acetyltransferase (Lyso-PAF-AT) of rabbit leukocytes (RLs), as well as on rabbit plasma-PAF-AH, the key enzymes of both de novo/remodelling PAF biosynthesis and PAF degradation, respectively. RESULTS: Several antibiotics inhibited PAF-induced platelet aggregation of both WRPs and rPRP in a concentration-depended manner, with clarithromycin, azithromycin and amikacin exhibiting the higher inhibitory effect, while when combined they synergistically inhibited PAF. Higher concentrations of all antibiotics tested were needed in order to inhibit PAF induced aggregation of rPRP, but also to inhibit thrombin induced aggregation of WRPs. Concentrations of these drugs similar to their IC50 values against PAF activity in WRPs, inhibited also in vitro PAF-CPT and Lyso-PAF-AT activities of rabbit leukocytes, while only clarithromycin and azithromycin increased rabbit plasma-PAF-AH activity. CONCLUSIONS: These newly found properties of antibiotics used in sepsis suggest that apart from their general actions, these drugs may present additional beneficial anti-inflammatory and anti-coagulant effects against the onset and establishment of sepsis by inhibiting the PAF/PAF-receptor and/or the thrombin/protease-activated-receptor-1 systems, and/or by reducing PAF-levels through both PAF-biosynthesis inhibition and PAF-catabolism induction. These promising in vitro results need to be further studied and confirmed by in vivo tests, in order to optimize the efficacy of antibiotic treatment in sepsis.

Calcific myonecrosis of the leg: report of three patients presenting with infection.

BACKGROUND: Calcific myonecrosis is a rare late complication of trauma, affecting almost exclusively the lower limb. Its radiologic appearance is characteristic. Superimposed infection usually is a sequela of biopsy. CASE REPORT: We present three patients, one with bilateral involvement, who presented with calcific myonecrosis and spontaneous infection. Three infections were attributable to a single microorganism: Enterobacter cloacae, Staphylococcus hominis, and S. haemolyticus were recovered. Multiple microorganisms were responsible in the other case. Treatment consisted of radical surgical debridement and antibiotics. The incision was closed over a suction drain, where possible, or left open to close by secondary intention. CONCLUSIONS: Calcific myonecrosis may present as infection without any obvious precipitating factor, and it should be included in the differential diagnosis in cases of soft tissue infection of the leg.

Anti-platelet-activating factor effects of highly active antiretroviral therapy (HAART): a new insight in the drug therapy of HIV infection?

Platelet-activating factor (PAF) is a potent inflammatory mediator, which seems to play a role in the pathogenesis of several AIDS manifestations such as AIDS dementia complex, Kaposi's sarcoma, and HIV-related nephropathy. PAF antagonists have been studied in these conditions with promising results. In order to examine the possible interactions between PAF and antiretroviral therapy, we studied the effect of nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and protease inhibitors against PAF biological activities and its basic biosynthetic enzymes dithiothreitol-insensitive PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (Lyso-PAF-AT), as well as its main degradative enzyme PAF-acetylhydrolase, of human mesangial cell line (HMC). We also studied the effect of several backbones and highly active antiretroviral therapy (HAART) regimens against PAF activity. Among the drugs tested, several inhibited PAF-induced platelet aggregation in a concentration-depended manner, with tenofovir, efavirenz, and ritonavir exhibiting the higher inhibitory effect. In addition, when these drugs were combined in backbones and HAART regimens based on American antiretroviral therapy proposals, they also synergistically exhibited an inhibitory effect against PAF-induced platelet aggregation. Several of these drugs have also inhibited in vitro microsomal PAF-CPT activity, and concentrations of lopinavir-r or tenofovir-DF (similar to their IC(50) against PAF-induced platelet aggregation) exhibited the same effect against PAF-CPT and Lyso-PAF-AT when added in the cell medium of cultured HMC. In addition, in naïve patients treated with one of the most potent anti-PAF HAART regimens (efavirenz/emtricitabine/tenofovir-DF) for a period of 1 month, a significant reduction of the specific activity of PAF-CPT of washed human leukocytes of these patients was also observed, compared with its levels before the HAART treatment. These promising results need to be further studied and confirmed by additional in vivo tests in order to optimize HAART efficacy.