Gammapatía biclonal transitoria posterior a infección por SARS-CoV-2. Reporte de un caso / Transient biclonal gammopathy after SARS-CoV-2 infection. A case report

Resumen Los pacientes infectados por SARS-CoV-2 presentan un curso clínico variable, desde asintomáticos o con síntomas respiratorios leves hasta una evolución grave con gran reacción inflamatoria e inmune. La aparición de un componente monoclonal como manifestación de este estado inflamatorio e inmune está poco descrito. Se presenta el caso de un paciente masculino de 74 años que inicia en 2020 con síndrome anémico, livedo reticularis y acrocianosis, gatillados por frío y aliviados por calor. El laboratorio evidencia anemia hemolítica por anticuerpos fríos y su estudio complementario es compatible con enfermedad por crioaglutininas. Se trata con rituximab sin respuesta, posteriormente recibe rituximab-bendamustina resolviendo síntomas, disminuyendo el título de crioaglutininas, mejorando la anemia y normalizando el perfil bioquímico. En febrero de 2022 presenta neumonía multifocal por SARS COV 2, requiriendo hospitalización por 19 días, con reactivación mínima de su enfermedad de base. En esta etapa se detecta en electroforesis e inmunofijación en suero dos componentes monoclonales IgG kappa e IgG lambda, sumados a su IgM kappa conocido por su enfermedad por crioaglutininas. El seguimiento muestra que dichos componentes persisten detectables por 4 meses, pero un control posterior evidencia la persistencia de sólo IgM kappa en inmunofijación, con desaparición de los nuevos componentes. La electroforesis es también negativa. Usualmente las infecciones virales generan hipergammaglobulinemias policlonales, en contraste mostramos como en este caso la infección por SARS-CoV-2 se asocia a gammapatía biclonal transitoria, la que planteamos como manifestación de la intensa reacción inmune generada por el virus.

Abstract Patients infected by SARS-CoV-2 present a variable clinical course, from asymptomatic or mild respiratory symptoms to a severe evolution with a major inflammatory and immune reaction. The appearance of a monoclonal component as a manifestation of this inflammatory and immune state is poorly described. We present the case of a 74-year-old male patient, who began in 2020 with anemic syndrome, livedo reticularis and acrocyanosis triggered by cold and relieved by heat. The laboratory showed hemolytic anemia due to cold antibodies and its complementary study was compatible with cold agglutinin disease. He was treated with rituximab without response, subsequently receiving rituximab-bendamustine, resolving symptoms, decreasing cold agglutinin titer, improving anemia and normalizing biochemical profile. In February 2022, he presented multifocal pneumonia due to SARS-CoV-2, requiring hospitalization for 19 days, with minimal reactivation of his underlying disease. At this stage, two monoclonal components IgG kappa and IgG lambda are detected in electrophoresis and immunofixation in serum, added to their IgM kappa known for cold agglutinin disease. The follow-up shows that these components remain detectable for 4 months, a subsequent control shows the persistence of only IgM kappa in immunofixation, with the disappearance of the new components. The electrophoresis is also negative. Usually viral infections generate polyclonal hypergammaglobulinemias, in contrast we show how in this case the SARS-CoV-2 infection is associated with transient biclonal gammopathy, which we propose as a manifestation of the intense immune reaction generated by the virus.

[Acute poisoning with methotrexate used as an abortifacient: description of 2 cases]. / Intoxicación aguda con metotrexato usado con fines abortivos: descripción de 2 casos.

Acute intoxication with methotrexate, used as an abortive, has not been described in Chile. We report two female patients, aged 15 and 24 years old, who presented with mucositis, erythrodermia, pancytopenia, and elevation of hepatic enzymes. Plasma methotrexate levels confirmed the clinical diagnosis and both patients were treated with high leucovorin doses and management of associated complications. In one patient, pregnancy continued, giving birth to a newborn with cranial, face and limb malformations. The second patient had a late rescue with leucovorin and was discharged with a persistent sensory motor neuropathy. Considering the severity of complications and that patients may deny its use, when there is reasonable clinical suspicion of methotrexate intoxication, leucovorin treatment should be started.

[Severe Henoch-Schonlein purpura in a patient with multiple myeloma]. / Púrpura de Schönlein-Henoch grave en un paciente con mieloma múltiple.

A Multiple Myeloma (MM), IgG-lambda stage III-A was diagnosed in a 41-year-old-man. After VAD cycles IgG decreased from 7.5 to 2.4 g/dL. were mobilized with cyclophosphamide and 10 micrograms/Kg G-CSF. Three days after the collection of peripheral stem cell, the patient had fever, nausea, vomiting, liquid stools, shoulder and knee arthralgia and dehydration. Upper GI endoscopy showed esophageal candidiasis and ulcerative necrotic lesions both in stomach and duodenum; the biopsy confirmed necrosis. Simultaneously, the appearance of purpura with maculopapular lesions of diverse sizes appeared in the feet progressing to the limbs and trunk. Hematuria and proteinuria were also observed. Skin biopsy showed leukocytoclastic vasculitis. Renal biopsy showed focal and segmental glomerulonephritis. Serum ANCA, cryoglobulins, anti-HCV and RF were negative, and serum monoclonal IgG was 1290 mg/dL. Daily treatment with i.v. methylprednisolone pulses for 3 days improved skin lesions and digestive involvement. Macroscopic hematuria and proteinuria improved after two months of steroid treatment.

[A case of neutropenia and agranulocytosis induced by clozapine. The importance of a drug surveillance program for their early detection]. / Un caso de neutropenia y agranulocitosis inducidas por clozapina. Importancia de un programa de farmacovigilancia para su detección precoz.

Clozapine is an atypical antipsychotic drug with a very low incidence of extrapyramidal effects, used in the treatment of schizophrenic patients refractory or intolerant to classical neuroleptics. Its use is limited due to the potential risk of producing agranulocytosis in 1 to 2% of patients. Despite the severity of this complication, the Federal Drug Administration allowed its use as long as its prescription is associated to a drug surveillance program that controls regularly the white cell count of patients using the drug. Three hundred three patients (210 male) have been admitted to a clozapine drug surveillance program. Two patients had a transitory leukopenia with less than 2000 leukocytes/ml and less than 1000 neutrophyls/ml, that reverted after discontinuing the drug. One patient, whose case is described, had a severe agranulocytosis with less than 500 neutrophyls/ml that required hospital admission.

[Changes in coagulation in patients with sepsis]. / Alteraciones de la coagulación en pacientes con sepsis.

Aiming to know the coagulation disorders that occur in patients with sepsis, a retrospective study of 75 such patients hospitalized in an Intensive Care Unit was performed. The coagulation profile requested by the attending physician, that included platelet count, prothrombin time, partial thromboplastin time, thrombin time, protamine sulphate test, fibrinogen and euglobin lysis time, was analyzed. Fourteen patients that were receiving prophylactic subcutaneous heparin were excluded from further analysis. Of the 61 remaining patients, 23 had hemorrhagic manifestations and 94.4% of these had multiple alterations in coagulation parameters. Eighty one percent of patients had abnormal prothrombin time and 73% thrombocytopenia. Isolated alterations were infrequent and consisted in thrombocytopenia (3.7%) and fibrinogen elevation (1.9%). Fifty two percent of patients had shock and they had significantly lower platelet counts and higher prothrombin and thrombin times than patients without hemodynamic disturbances. Global mortality was 63.9%. No relation between coagulation disturbances and mortality was observed. Likewise, no differences in mortality between patients with or without shock was observed. It is concluded that coagulation is frequently disturbed in patients with sepsis, even without clinical hemorrhagic symptoms, that these abnormalities are more marked in patients in shock and that 53% of these are consistent with intravascular coagulation.

[Platelet labelling with In-111-oxine: platelet survival and the images]. / Marcación de plaquetas con In-111-oxina: sobrevida plaquetaria e imágenes.

We studied 10 male and 2 female normal non-smoker volunteers (mean age 25) by labeling of autologous platelets with 111-In oxine. Daily samples for platelet survival were obtained in all, gamma-camera images in 10 and blood pool digital subtraction with 99m-Tc labeled erythrocytes in 6. Mean platelet count was 594 +/- 235 10(3)/mm3; collagen platelet aggregation pre and post labeling was 74 +/- 4.8 and 70 +/- 10%, respectively. Mean labeling efficacy was 65 +/- 15.4%, mean labeling dose was 201 +/- 79.5 microCi. A linearized initial survival of 7.9 +/- 1 day was obtained. Scintigraphic images showed circulating activity, greater in the spleen, persisting after digital subtraction. The method described can be used for clinical evaluation of platelet disorders and thrombosis.

[Cytogenetic study of acute and chronic leukemias]. / Estudio citogenético en leucemias agudas y crónicas.

From 1983 to 1987 we studied 30 patients with leukemia searching for chromosomal alterations. Cytogenetic studies of bone marrow showed an abnormal karyotype in 19 (67%). Seven out of 14 cases of acute leukemia presented different chromosomic alterations. The Philadelphia chromosome was found in 11 patients with chronic myeloid leukemia and 3 patients with chronic lymphatic leukemia; a Pseudo-Philadelphia chromosome was present in one patient, this being the first such finding in Chile. Thus, the karyotype is a valuable complementary study not only in chronic myeloid leukemia but also in chronic lymphatic leukemia and the acute lymphoblastic and non-lymphoblastic varieties.

Ascitic fluid triggering disseminated intravascular coagulation.

Seis pacientes con cirrosis hepatica, demostrada por biopsia y ascitis refactaria al tratamiento con diureticos fueron sometidos a un procedimiento de ultrafiltracion y reinfusion de liquido ascitico por periodos continuos que fluctuaron de 5 a 49 horas. Cinco de ellos presentaban alteraciones previas de la coagulacion, sin coagulacion intravascular diseminada (CID) Tres desarrollaron CID durante el tratamiento, que desaparecio espontaneamente, cuando se suspendio la reinfusion del liquido ascitico. Se efectuaron estudios in vitro del liquido de ascitis de 20 pacientes con cirrosis hepatica, diecisiete casos mostraron acortamiento del tiempo de tromboplastina parcial activado. El promedio de los 20 casos fue de 45.90 +/- 3.40 segs. comparando con un control con solucion salina: 50.85 +/- 3.95 segs (p < 0.001). En cuatro de estos 17 casos se demostro la accion procoagulante que fue ejercida sobre uno o mas de los factores plasmaticos de la coagulacion. Es recomendable efectuar un estudio in vitro del liquido ascitico antes de realizar su reinfusion, ya por medio de un procedimiento de ultrafiltracion y reinfusion o de una derivacion peritoneovenosa