Immunoadsorption therapy for a meningococcemia patient with myocarditis, adrenal hemorrhage, and purpura fulminans: a case report

Abstract Neisseria meningitidis, also known as meningococcus, is a relatively uncommon cause of invasive infection, but when it occurs, it is frequently severe and potentially life-threatening. A ten-year-old female patient developed a purpuric rash with fever. Upon arrival to the pediatric intensive care department, she was unconscious and in a poor general condition. We combined treatment with antibiotics, volume resuscitation, hydrocortisone, and CytoSorb® therapy resulted in a stabilization of hemodynamics, as well as control of hyperinflammation. We observed a significant decrease in vasopressor dosage in this patient.

Renal histological findings in a patient with acute renal injury associated with purpura fulminans: a case report / Achados histológicos renais em paciente com injúria renal aguda associada à purpura fulminans: relato de caso

ABSTRACT Introduction: Purpura fulminans (PF) is a rapid progressive thrombotic disease in which hemorrhagic infarction of the skin and disseminated intravascular coagulation (DIC) occurs. It can potentially cause acute kidney injury (AKI). However, there is no description in the medical literature of renal histological findings of PF. Case report: A 20-year-old female patient, previously healthy, was admitted to the emergency department (ED) with odynophagia, fever, generalized myalgia and anuria, which evolved with the appearance of purpuric plaques on the face and limbs. She required dialysis on admission. Laboratorial tests showed anemia, leukocytosis, thrombocytopenia, and elevation of lactic dehydrogenase (LDH). The purpuric lesions became bullous with ruptures and then necrotic and erosive, reaching the dermis, subcutaneous tissue and musculature, until bone exposure. There was no improvement with initial antibiotic therapy aimed at the treatment of meningococcemia. Thrombotic microangiopathy (TMA) and PF were then suspected. The patient remained in daily dialysis, requiring plasmapheresis. After sustained improvement of the thrombocytopenia, she underwent renal biopsy, which was not compatible with TMA, characterizing possible PF. A complete recovery of the renal function was achieved and cutaneous sequels were treated with grafts. Conclusion: When thrombotic and hemorrhagic phenomena overlap, obtaining a renal biopsy can be difficult. However, in the presented case, the biopsy allowed the exclusion of AKI caused by TMA, presenting for the first time, histological findings compatible with PF.

RESUMO Introdução: Purpura Fulminans (PF) é uma doença trombótica de rápida progressão, com infarto hemorrágico da pele e coagulação intravascular disseminada (CIVD). É potencialmente causadora de injúria renal aguda (IRA). Porém, não há descrição na literatura médica dos achados histológicos renais causados por PF. Relato de caso: Mulher, 20 anos, previamente hígida, hospitalizada por odinofagia, febre, mialgia generalizada e anúria, evoluiu com aparecimento de placas purpúricas em face e membros. Necessitou de hemodiálise (HD) já na admissão. Exames laboratoriais mostravam anemia, leucocitose, plaquetopenia e elevação de desidrogenase lática. As lesões purpúricas tornaram-se bolhosas com rompimento e progressão para necrose, se aprofundaram, atingindo derme, subcutâneo e musculatura, até a exposição óssea. Não houve melhora com antibioticoterapia inicial voltada para tratamento de meningococemia. Suspeitou-se, então, de microangiopatia trombótica (MAT) e PF. A paciente permaneceu em HD diária e necessitou também de plasmaférese, após melhora sustentada da plaquetopenia, foi submetida à biópsia renal, que não foi compatível com MAT, possivelmente caracterizando PF. Houve recuperação completa da função renal e as sequelas cutâneas foram tratadas com enxerto. Conclusão: Em casos nos quais os fenômenos trombóticos e hemorrágicos se sobrepõem, a obtenção da biópsia renal se torna difícil. Neste caso, a biópsia permitiu excluir IRA causada por MAT e mostrar, pela primeira vez, achados compatíveis com PF.

Pigmented purpura and cutaneous vascular occlusion syndromes

Abstract: Purpura is defined as a visible hemorrhage in the skin or mucosa, which is not evanescent upon pressure. Proper classification allows a better patient approach due to its multiple diagnoses. Purpuras can be categorized by size, morphology, and other characteristics. The course varies according to the etiology, as do the diagnostic approach and treatment. This review discusses pigmented purpuras and some cutaneous vascular occlusion syndromes.

Purpura fulminans related to paroxysmal nocturnal haemoglobinuria: a case report and literatures review / 中华血液学杂志

Objective: To improve the understanding of the rare clinical presentation and management of purpura fulminans (PF) in patients with paroxysmal nocturnal haemoglobinuria (PNH). Methods: A case of PF occurring in PNH is reported, while the related literature review is conducted. Results: A 49-year-old male patient suffered from one-week history of fever, greenish-brown colour urine, multiple well demarcated and painful purpura of the head and neck. He had been reported to have two thromboembolic events during the 22-year course of PNH. Skin biopsy displayed classic PF features. Laboratory testing showed a high PNH clone, intravascular hemolysis and coagulation system changes. After sufficient anticoagulation and short course of glucocorticoid therapy, the clinical conditions were improved correspondingly. During a follow-up period of 6 month, there was no recurrence of thrombosis. Conclusion: PF should be considered in PNH patients with unexplained, quickly developed painful purpura. Extensive work-up should be performed to find out other potential thrombophilic risk factors after diagnosis of PF. Early diagnosis, adequate anticoagulation therapy and control hemolysis were essential to PF treatment occurring in PNH. The survival of patients and the qualities of life can be improved. The PNH clone detection is needed to evaluate the status of procoagulation and predict the risk of recurrent thrombosis.

Cerebral Palsy due to Intracranial Hemorrhage Caused by Consumptive Coagulopathy in Protein C Deficiency: A Case Report / 대한소아신경학회지

Protein C (PROC) is a potent anticoagulant inactivating coagulation factors Va and VIIIa. PROC deficiency is very rare condition inherited as an autosomal dominant or recessive trait, and associated with various thromboembolic and ischemic conditions. Moreover, severe form of PROC deficiency can cause fatal hemorrhagic complications due to consumptive coagulopathy. We reported two children with hemorrhagic stroke who were diagnosed as severe PROC deficiency caused by two different types of compound heterozygous PROC gene mutations. We described results of laboratory tests, genetic analysis, brain magnetic resonance images, and functional outcomes. Both children received prophylactic anticoagulation therapy and presented with purple-colored skin lesions during rehabilitation. Purpura fulminans caused by insufficient anticoagulation should be differentiated from hematoma caused by excessive anticoagulation therapy in these children.

Cerebral Palsy due to Intracranial Hemorrhage Caused by Consumptive Coagulopathy in Protein C Deficiency: A Case Report / 대한소아신경학회지

Protein C (PROC) is a potent anticoagulant inactivating coagulation factors Va and VIIIa. PROC deficiency is very rare condition inherited as an autosomal dominant or recessive trait, and associated with various thromboembolic and ischemic conditions. Moreover, severe form of PROC deficiency can cause fatal hemorrhagic complications due to consumptive coagulopathy. We reported two children with hemorrhagic stroke who were diagnosed as severe PROC deficiency caused by two different types of compound heterozygous PROC gene mutations. We described results of laboratory tests, genetic analysis, brain magnetic resonance images, and functional outcomes. Both children received prophylactic anticoagulation therapy and presented with purple-colored skin lesions during rehabilitation. Purpura fulminans caused by insufficient anticoagulation should be differentiated from hematoma caused by excessive anticoagulation therapy in these children.

Trombosis en el recién nacido / Thrombosis in newborn infants

La probabilidad de padecer trombosis es mucho mayor en el período neonatal que en cualquier otra etapa pediátrica. La labilidad del particular sistema hemostático del neonato, sumada a los múltiples factores de riesgo a que está expuesto y la presencia casi constante de catéteres, son responsables de este hecho. Las trombosis venosas son más frecuentes que las arteriales y ocurren principalmente en los miembros, la aurícula derecha y las venas renales. El accidente cerebrovascular puede ser causado por la oclusión del flujo arterial que llega al cerebro o del sistema de drenaje venoso de este. La púrpura fulminans es una patología de altísima gravedad, que debe ser considerada una emergencia médica y se debe a la deficiencia grave de proteína C o, menos frecuentemente, de proteína S o antitrombina. La mayoría de los episodios trombóticos tienen indicación de tratamiento anticoagulante, que se puede realizar con heparina no fraccionada y/o con heparina de bajo peso molecular. La púrpura fulminans requiere terapia de sustitución con proteína C y/o plasma fresco. El tratamiento trombolítico se realiza con activador tisular del plasminógeno y debe quedar reservado solo para aquellas trombosis cuya localización implique compromiso de vida o pérdida de un órgano o de un miembro.

The incidence of thrombosis is higher among newborn infants than in any other stage of pediatric development. This fact is the consequence of labile characteristics of the neonatal hemostatic system, in addition to exposure to multiple risk factors and the wide use of vascular catheters. Venous thromboses, which mainly affect the limbs, the right atrium and renal veins, are more frequently seen than arterial thromboses. A stroke may be caused by the occlusion of the arterial flow entering the brain or by occlusion of its venous drainage system. Purpura fulminans is a very severe condition that should be treated as a medical emergency, and is secondary to severe protein C deficiency or, less frequently, protein S or antithrombin deficiency. Most thrombotic events should be managed with antithrombotic therapy, which is done with unfractionated and/or low molecular weight heparins. Purpura fulminans requires protein C replacement and/or fresh frozen plasma infusion. Thrombolytic therapy is done using tissue plasminogen activator and should only be used for life-, or limb-, or organ-threatening thrombosis.

Deficiencia congénita de proteína C en un recién nacido con trombosis y necrosis de tejidos extensa / Congenital C protein deficiency in a newborn with extensive thrombosis and necrosis of tissues

Uno de los trastornos hematológicos más graves del período neonatal es la deficiencia congénita de proteína C, de presentación muy rara, y causa de enfermedad tromboembólica severa y púrpura fulminante en recién nacidos. Se puede sintetizar como una entidad clínico-patológica, de aparición aguda, con trombosis de la vasculatura de la dermis, lo cual conduce a necrosis hemorrágica y progresiva de la piel, asociada a coagulación intravascular diseminada y hemorragia perivascular, que ocurre en el período neonatal. El paciente presentado exhibe los elementos clínico-patológicos que caracterizan la púrpura fulminante, cuyo origen se debe a una deficiencia hereditaria de proteína C, lo cual condujo a la aparición de complicaciones trombóticas severas(AU)

One of the most serious hematological disorders of the neonatal period is congenital C protein deficiency of very rare occurrence and the main cause of severe thromboembolic disease and purpura fulminans in newborns. It may be summarized as a clinical and pathological entity of acute occurrence, with dermis vasculature thrombosis that leads to progressive hemorrhagic necrosis of the skin, associated to disseminate intravascular coagulation and perivascular hemorrhage in the neonatal period. The patient of this report showed the clinical and pathological elements characterizing purpura fulminans the origin of which is due to hereditary C protein deficiency that led to onset of severe thrombotic complications in this patient(AU)

Lifetime cost of meningococcal disease in France: Scenarios of severe meningitis and septicemia with purpura fulminans

Invasive meningococcal disease [IMD] is life-threatening and can result in severe sequelae. In France, no data have been published on the costs of severe IMD cases. Two realistic scenarios were developed with national experts [clinicians and social workers]: a 6-year-old child with purpura fulminans with amputation of both legs below the knee [case A] and a 3-year-old with meningitis and severe neurological sequelae [case B]. Additional scenarios included other typical sequelae of IMD such as chronic kidney disease [CKD] profound deafness and epilepsy. Data on healthcare, disability, educational and other resource use were obtained from experts and families of patients with similar sequelae. Unit costs [2013] were mainly obtained from the literature and the National Health Insurance [NHI]. Time horizon was based on life expectancies of patients [77 and 55 years, respectively]. A 4% discount rate decreasing to 2% after 30 years was applied. Costs are presented from the perspective of the NHI, publicly funded organizations and patients' families or their private health insurances, purpura fulminans with amputations is associated with a lifelong discounted cost of €768,875. Adding CKD doubles the amount [€ 1,480,545]. Meningitis with severe neuro-cognitive sequelae results in a lifelong discounted cost of €1,924,475. Adding profound deafness and epilepsy slightly increases the total cost [€2,267,251]. The first year is the most expensive in both scenarios [€166,890 and €160,647 respectively]. The main cost drivers for each scenario are prostheses and child/adult stays in healthcare facilities, respectively. Overall, patients' families or his private insurance had to pay around 13% of total cost [101,833€ and 258,817€, respectively]. This study fills a gap in the body of knowledge on IMD sequelae care and lifetime costs in France. The potentially high economic burden of IMD, in addition to its physical, psychological and social burden, reinforces the need for prevention

Diagnosis of Severe Protein C Deficiency Confirmed by Presence of Rare PROC Gene Mutation

Protein C (PROC) deficiency is caused by mutations in the PROC gene on chromosome 2q14.3. Patients with PROC deficiency typically present distinguished purpura, intracerebral and intravascular coagulopathy, and ophthalmologic complications. Here, we report a rare severe form of PROC deficiency resulting from a compound heterozygosity in PROC. The patient was a 5-day-old female neonate born at 39 weeks of gestation with a birth weight of 2,960 g. She was transferred to our hospital with running a fever at 38.5℃ and with dark red patches on her feet. At admission, a complete blood count showed no specific findings, but levels of PROC and protein S were abnormally low (1% and 68%, respectively). Magnetic resonance imaging revealed intracerebral hemorrhaging and parenchymal damage with dysplasia of the brain. Ophthalmologic examination revealed vitreous hemorrhaging with retinal detachment. Genetic testing revealed a missense mutation (Arg211Trp) and a frameshift mutation (Gly239Serfs*8) in PROC, inherited from the father and mother, respectively. The patient recovered from purpura after undergoing ventriculoperitoneal shunting and treatment with fresh frozen plasma, warfarin sodium, and PROC concentrate. This is the first report of severe neonatal PROC deficiency with purpura fulminans, vitreous hemorrhage, and intracerebral hemorrhage confirmed via PROC genetic testing, which identified a rare compound heterozygosity of PROC.

Uso de doble colgajo diep para reconstrucción de extremidad inferior / Double diep flap for lower extremities reconstruction

Introduction: A soft tissue defect considering the extent, location, depth and involved structures can be a complex task, leading to search for unusual reconstructive alternatives. Case report: Puerperal woman, 21 years, previously healthy, admitted for septic shock and skin necrosis of both extremities secondary to purpura fulminans. Escharectomy was performed and the final defect was 27 percent of total body surface, corresponding to necrotic areas of both superior and lower extremities. Is remarkable the presence of musculocutaneous perforating vessels thrombosis and segmental muscular necrosis in legs and interosseous muscles necrosis in hands. In upper extremity coverage was performed with dermoepidermal grafts. To cover peroneal malleolus and feet dorsum, whereas there were no regional or local alternatives, we realize a double DIEP flap. Flap elevation of bilateral DIEP flap was performed simultaneously for two surgical teams. The patient had no complications and was discharged with complete soft tissue coverage.

Introducción: Un defecto de cobertura extenso de extremidades inferiores (EEII), considerando ubicación, profundidad y estructuras involucradas es de una alta complejidad y puede llevar a buscar alternativas reconstructivas poco habituales. Caso Clínico: Paciente de 21 años, puérpera, ingresa por shock séptico y necrosis cutánea extensa de extremidades secundario a un purpura fulminans. Se realiza escarectomía y el defecto resultante es de 27 por ciento de superficie corporal, correspondiendo a zonas necróticas en ambas extremidades, superiores e inferiores. Destaca la presencia de trombosis de vasos perforantes musculocutáneos, necrosis muscular segmentaria en piernas y de musculatura interósea en manos. En extremidades superiores se realizó cobertura con injertos dermoepidérmicos. Para la exposición de ambos maléolos peroneos y dorso de pies, considerando que no existen alternativas locales ni regionales, se decide realizar un colgajo DIEP bilateral; se eleva en un tiempo, con dos equipos quirúrgicos simultáneos. La anastomosis microquirúrgica se realizó a los vasos tibiales de cada extremidad. La evolución postoperatoria fue favorable. La paciente es dada de alta en buenas condiciones generales, extubada, con cobertura cutánea completa.

Staphylococcal Bacteremia and Purpura Fulminans.

Purpura fulminans (PF) is a life threatening disorder of acute onset characterized by cutaneous hemorrhage and necrosis caused by DIC and dermal vascular thrombosis. It is commonly associated with meningococcemia or invasive streptococcal disease. In this article we report a case of purpura fulminans in the setting of staphylococcus aureus infection.

Asplenia congénita y purpura fulminans neumocóccico en paciente pediátrico: reporte de caso con necropsia y revisión del tema / Congenital asplenia and pneumococcal purpura fulminans in a pediatric patient: case report with pathological findings and review

Absent or defective splenic function is associated with a high risk of fulminant bacterial infections, especially due to encapsulated bacteria. Not knowing this condition may delay medical treatment. Streptococcus pneumoniae is the leading cause of sepsis in these patients. Asplenic patients are at high risk for septic shock and eventually purpura fulminans, a life-threatening condition. We report the case of a 3 years oíd girl, with mitral stenosis and recurrent pneumonía that was admitted due to fever but in the next few hours presented hypotension, purpura and livedo reticularis. Laboratory test showed leucopenia (3.400/mm³), bandemia (43 percent of immature forms), thrombocytopenia, hypoprothombinemia and severe lactic acidosis (ph: 7.0 and lactic acid 11 mmol/1). The patient developed septic shock and multiorganic failure. Mechanical ventilation, volume resuscitation, vasoactive drugs and antibiotic therapy was initiated. Ultrasound was performed on the second day, demostrating asplenia. Peripheral blood smear showed Howell-Jolly bodies. Patient had a positive blood culture for penicillin-resistant Streptococcus pneumoniae (serotype 19F). Patient died of intracerebral hemorrhage after 8 days of admission. Necropsy confirmed asplenia and bilateral suprarenal haemorrhage. Absence of spleen can lead to life threatening infections, it is important to recognize it because vaccination and antibiotic prophylaxis can provide life-saving protection. This case provides a reminder to pursue asplenia as a potential underlying mechanism for invasive bacterial infection in children.

La condición de asplenia predispone a infecciones invasoras por bacterias capsuladas. Desconocer previamente ese antecedente dificulta y retarda el tratamiento médico. Streptococcus pneumoniae es el agente habitualmente causal de sepsis en estos pacientes. Los individuos asplénicos son particularmente proclives a evolucionar con shock séptico y eventual-mente al desarrollo de purpura fulminans, entidad altamente letal. Comunicamos el caso de una paciente con 3 años de edad y antecedente de cardiopatía y neumonías a repetición. Ingresó con compromiso sensorial, febril, hipotensa, con púrpura y livedo reticularis. En los exámenes de laboratorio destacaba la presencia de leucopenia (3.400/ mm³) trombopenia e hipoprotrombinemia (39 por ciento). Se inició ventilación mecánica, reanimación con volumen, fármacos vasoactivos y antibioterapia con vancomicina, clindamicina y ceftriaxona. Evolucionó con shock séptico refractario y síndrome de disfunción orgánica múltiple. Al segundo día de evolución una ecograña de abdomen comprobó la ausencia de bazo. En el frotis sanguíneo se evidenciaron corpúsculos de Howell-Jolly. Hemocul-tivo (+) S. pneumoniae resistente a penicilina (serotipo 19F). Un infarto hemorrágico cerebral ocasionó su deceso al octavo día. El estudio necrópsico corroboró la asplenia y evidenció necrohemorragia suprarrenal bilateral. La sepsis en un paciente asplénico puede ser de alguna forma prevenible mediante profilaxis antimicrobiana y vacunación neumocóccica. Dado los antecedentes de la paciente la búsqueda de asplenia era fundamental.

Spectrum of purpura fulminans.

Purpura Fulminans is a severe disorder of acute onset with high morbidity and mortality. It is characterized by DIC with thrombocytopenia, hyofibrinogenemia, hypothrombinemia and anemia. It most often occurs in young with sudden appearance of symmetrical, tender, ecchymotic skin lesions usually involving the lower extremities. An infectious and noninfectious etiology has been proposed. Early recognition and early therapy with appropriate antibiotics and heparin is known to limit both morbidity and mortality. This article reports 5 cases of Purpura Fulminans treated at our centre with review of etiology, pathogenesis, clinical features and treatment.

Rare presentation of a common disease of tropics.

A 19 years male presented with fever, oliguria and purpuric lesions involving both hands. The patient was diagnosed as a case of purpura fulminans with disseminated intravascular coagulation due to complicated falciparum malaria. The case is presented to sensitize the physicians to keep malaria as a differential in cases of fever with purpura fulminans.

A Case of Meningococcal Infection necessitating Amputation of Both Legs in a Child / 감염과화학요법

Meningococcal sepsis-associated purpura fulminans is a rapidly progressing condition with high morbidity and mortality. There are several reports of amputation of extremities due to gangrenous change in this condition. However, in Korean literature, we found only one case report associated with amputation of one leg due to meningococcal infection. We report a case of meningococcal infection necessitating the amputation of both legs in a previously healthy seven-year-old girl with a review of literatures.

A Case of Meningococcal Infection necessitating Amputation of Both Legs in a Child / 감염과화학요법

Meningococcal sepsis-associated purpura fulminans is a rapidly progressing condition with high morbidity and mortality. There are several reports of amputation of extremities due to gangrenous change in this condition. However, in Korean literature, we found only one case report associated with amputation of one leg due to meningococcal infection. We report a case of meningococcal infection necessitating the amputation of both legs in a previously healthy seven-year-old girl with a review of literatures.

Surgical Treatment Guideline of Meningococal Induced Purpura Fulminans

PURPOSE: Purpura fulminans is a rare but rapidly progressive, serious, often life-threatening disorder in childhood, which is complicated with septic shock or disseminated intravascular coagulopathy during acute infection. It occurs first as acute-onset petechial rash, and spreads rapidly into full thickness skin and soft tissue necrosis. In the past, it had high mortality rate, up to 80%, but recently, survival rate has increased due to early diagnosis, and rapid advancement of critical care and antibiotics. From our experiences of PF management, we would like to review the pathophysiology and suggest the surgical treatment guideline about meningococcal induced purpura fulminans. METHODS: Two cases of purpura fulminans over the last 3 years were reviewed retrospectively about reconstructive management. After they were treated resuscitative management initially by the critical intensive care, reconstructive surgery was performed by plastic surgeon as soon as the patients were vitally and mentally stable. RESULTS: There were 6 procedures in case 1, and 3 procedures in case 2. The mean delayed period from admission with sepsis to the first surgical debridement was 24 days and 42 days, respectively. Total hospitalization period was 103 days and 69 days, respectively. All of them were treated with debridement and split thickness skin graft, but delayed debridement was superior to early one in the point of preserving much more tissues. CONCLUSION: From our experience, we suggest that conservative therapy to the wounds appears to be the best tool in the initial vitally unstable period in order to preserve as much tissues and functions as possible if no active inflammation and compartment syndrome are detective.