RESUMEN
BACKGROUND: Hereditary angioedema with normal C1-inhibitor (HAE-nC1-INH) is a rare genetic disease with similar phenotype to HAE-C1-INH but different genetic background. Currently, 6 subtypes are recognized, based on the underlying mutations. Several aspects need further clarification. OBJECTIVE: To assess clinical features of patients with genetically characterized HAE-nC1-INH from the North of Portugal. METHODS: Retrospective assessment of clinical data from all patients with HAE-nC1-INH followed at a HAE Reference Center. RESULTS: A total of 41 patients were identified, 4 with no family history. The FXII mutation Thr328Lys (38 carriers) was the most prevalent. There were 3 new potentially disease-causing variants linked to HAE-nC1-INH identified (c.529+4A>G:FXII; Cys248*:Kininogen-1; and Arg261His:Plasminogen). The HAE-FXII cohort included 82% females and 71.8% symptomatic patients. Penetrance rate was significantly higher in females (81.3% vs 28.6%; P = .012). A hormonal influence was observed in 96.2% of the symptomatic females, although 62.5% remained symptomatic after oral estrogen withdrawal. Trauma and dental procedures were frequent triggers (82.6% and 45.5%, respectively). Main locations were facial (described by 96%), lips (82.1%), and eyelids (64.3%). One patient reported erythema marginatum as prodrome. Plasma-derived C1-INH was effective as short-term prophylaxis in all treated patients, but only in 80% as on-demand treatment. Icatibant was effectively used on demand in 9 patients, but with relapses in 5 (57%). CONCLUSION: We described a large Portuguese series of patients with HAE-nC1-INH genetically characterized. Differences with others may contribute to improve current unmet needs and raise awareness of this rare disease. We highlighted the identification of 3 new variants (additional molecular studies are ongoing) and the report of erythema marginatum in HAE-nC1-INH.
Asunto(s)
Angioedemas Hereditarios , Proteína Inhibidora del Complemento C1 , Humanos , Femenino , Masculino , Portugal/epidemiología , Adulto , Proteína Inhibidora del Complemento C1/genética , Proteína Inhibidora del Complemento C1/uso terapéutico , Estudios Retrospectivos , Angioedemas Hereditarios/genética , Angioedemas Hereditarios/tratamiento farmacológico , Angioedemas Hereditarios/diagnóstico , Persona de Mediana Edad , Adolescente , Adulto Joven , Niño , Mutación , Anciano , Factor XII/genética , FenotipoAsunto(s)
Pustulosis Exantematosa Generalizada Aguda , Dermatitis Alérgica por Contacto , Síndrome de Hipersensibilidad a Medicamentos , Humanos , Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/etiología , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/complicaciones , Dermatitis Alérgica por Contacto/complicacionesRESUMEN
Recurrent outbreaks of oral infection and isolated cases characterize the new epidemiological scenario of Chagas disease (CD) in the Brazilian Amazon. Acute Chagas disease (ACD) is common in Pará and Amazonas, Northeastern and Northwestern Brazilian Amazonia. In the present study, we describe the first molecularly characterized autochthonous case of ACD in Rondônia, Southwestern Amazonia. The patient, a 39-year-old male resident in the small city of Cujubim, presented typical ACD symptoms: fever, asthenia, myalgia, progressive dyspnea, swelling of the legs, and tiredness at minimal efforts, all compatible with ACD and indicative of cardiac involvement. A thick blood drop test revealed trypomastigote forms of Trypanosoma cruzi genotyped as TcIV. An epidemiological investigation ruled out oral infection, and support for vectorial transmission included the finding of Panstrongylus geniculatus positive for T. cruzi (TcIII and TcIV) inside the tent used by the patient when harvesting forest timber, and a circular cutaneous lesion resembling a chagoma of inoculation. Treatment with benznidazole led to blood parasite clearance as confirmed by molecular tests. Altogether, our findings fitted well into the ecological scenario where deforestation and colonization of forested areas represent an important risk factor to the adaptation of P. geniculatus to human habitats, favoring vectorial transmission of CD in the Amazonian region.
Asunto(s)
Enfermedad de Chagas , Panstrongylus , Trypanosoma cruzi , Animales , Brasil/epidemiología , Enfermedad de Chagas/veterinaria , Genotipo , Humanos , Masculino , Panstrongylus/parasitología , Trypanosoma cruzi/genéticaRESUMEN
Acquired Hemophilia A (AHA) is a rare autoimmune disorder, caused by the development of circulating autoantibodies against coagulation factor VIII (FVIII). AHA is associated with bullous pemphigoid in 2% of patients. We report a case of a 74-year-old man admitted with anemia and a tense subcutaneous and muscular hematoma in the right thigh. Blood analysis confirmed AHA. The patient had a recent diagnosis of bullous pemphigoid. Response to bypass agents and corticosteroids was good with bleeding control and normalization of FVIII and negative autoantibodies, respectively. In a 3-month follow-up period after tapering and stopping prednisolone, a relapse occurred, and immunosuppression was reinitiated. An early diagnosis and effective treatment in AHA are essential to reduce morbimortality. A careful tapering of immunosuppression is important to minimize FVIII inhibitor recurrence, as observed in this case.