Waterhouse-Friderichsen Syndrome Research Articles

Transient Waterhouse-Friderichsen Syndrome in a Child: A Case Report

Waterhouse-Friderichsen syndrome (WFS) is a rare but usually fatal disease characterized by adrenal insufficiency associated to bilateral adrenal hemorrhage. It can be associated both to non-infection and a variety of infectious diseases, among which sepsis from Neisseria meningitidis accounts for more than 80% of cases. We report the case of an otherwise healthy 2-year-old child who had a WFS as a consequence of Neisseria meningitidis infection and in which we witnessed a complete recovery of adrenal function a few months after the event. The case highlights not only the difficulty of diagnosing this syndrome but also, at the same time, the extreme importance of high suspicion, early treatment, a multidisciplinary approach and, most of all, the importance of verifying the restoration of adrenal function in order to achieve a better quality of life. Int J Clin Pediatr. 2021;10(1):28-33 doi: https://doi.org/10.14740/ijcp429

Waterhouse-Friderichsen syndrome: an endocrine emergency

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

MON-LB067 AAA Syndrome in a 30 Year Old Man Presenting for Primary Adrenal Insufficiency Management

AAA syndrome or Allgrove Syndrome is a rare autosomal recessive congenital disease characterized by the triad of adrenal insufficiency (Addison's disease), failure of the lower esophageal sphincter to relax (achalasia) and absence of tear secretion (alacrima). The syndrome is frequently seen in childhood. Here we describe a 30 year old man who presented to an adult endocrinology clinic for continued management of primary adrenal insufficiency, which had been diagnosed at age 2 and considered a sequela of a disseminated meningococcal infection (Waterhouse-Friderichsen syndrome). He had been treated chronically with cortisone acetate and fludrocortisone. Multiple subsequent hospitalizations for treatment of adrenal crises occurred in childhood. Dysphagia associated with poor weight gain was present since birth. There had been an absence of tear production. An ACTH level was elevated, and cosyntropin administration had failed to augment the serum cortisol level. He has had negative Schirmer test, distal esophageal narrowing on barium esophagram and multiple esophageal dilation therapy for treatment of achalasia. AAAS gene sequencing showed homozygous mutations of AAAS gene on chromosome 12q13 which encodes ALADIN. Based on clinical features and investigation noted upon presentation to our clinic, followed by genetic testing, the diagnosis of AAA syndrome (or Allgrove syndrome) was made. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

A four months infant survival case of waterhouse-friderichsen syndrome

A four months infant survival case of waterhouse-friderichsen syndrome

JOURNAL OF PEDIATRIC CRITICAL CARE

Staphylococcal toxic shock syndrome (TSS) is a rare and potentially fatal multi system dysfunction. The syndrome occurs primarily due to TSS Toxin-1 (TSS-1) liberated by Staphylococcus aureus (SA). Fever with rash followed by multi organ dysfunction in the form of acute kidney injury, raised liver transaminases and refractory hypotension indicates the possible diagnosis of a TSS, more commonly by Staphylococcus. Here, a 7 year old boy presented with all the features of toxic shock syndrome, developed hyponatremia, hyperkalemia, refractory hypoglycaemia and hypotension and succumbed within 12 hours of admission and ultimately was diagnosed to be a case of Staphylococcal toxic shock syndrome due to MSSA with Waterhouse Friderichsen Syndrome (WFS).

A Case of Waterhouse-Friderichsen Syndrome Resulting from an Invasive Pneumococcal Infection in a Patient with a Hypoplastic Spleen.

A 50-year-old male was brought to our emergency department by ambulance with complaints of pain and numbness in both legs. At arrival, purple spots were evident on his neck and face. Examination of the vital sign indicated septic shock. Laboratory data and blood gas analysis revealed disseminated intravascular coagulation, multiple organ failure, and metabolic acidosis. Peripheral blood smears revealed Howell-Jolly bodies, indicating decreased splenic function. A rapid urinary pneumococcal antigen test was also found to be positive. After admission to the intensive care unit, extensive treatment, including polymyxin-B direct hemoperfusion and administration of methylprednisolone and broad spectrum antibiotics was immediately initiated. Despite of our efforts to save his life, the patient died six hours after the arrival. The following day, blood cultures revealed the presence of Streptococcus pneumoniae. An autopsy revealed a hypoplastic spleen and a bilateral adrenal hemorrhage, indicating acute adrenal insufficiency caused by sepsis. Finally, the patient was diagnosed with Waterhouse-Friderichsen syndrome. Although severe infection may be seen in the splenectomized patients, it should be noted that patients with a hypoplastic spleen may have acute severe infections. We, therefore, report a case of Waterhouse-Friderichsen syndrome resulting from an invasive pneumococcal infection in a patient with a hypoplastic spleen.

Postmortem detection of Neisseria Meningitidis in a case of Waterhouse- Friderichsen syndrome from fulminant meningococcal disease in an adult patient

Waterhouse-Friderichsen syndrome (WFS) from meningococceal sepsis is a rare life-threatening condition which generally occur during infancy and childhood with a high mortality rate (from 10-30% up to 95%). It is very rare in the adult population, usually with pathological risk factors of invasive meningococcal infection. In such fatalities, the condition may rapidly progress into septic shock and disseminated intravascular coagulation with skin lesions (known as “purpura fulminans”) and early recognition and therapy is often difficult owing to the unspecific findings at onset. The purpose of this case report is to present an unusual case of WFS from fulminant meningococceal disease with no meningeal involvement in a previously healthy adult patient, unexpectedly associated with dysmegakaryocytopoiesis findings in bone marrow. The conclusive diagnosis was due to the detection of Neisseria Meningitidis in cerebrospinal fluid despite a postmortem interval of four days and the long cadaver refrigeration.

Waterhouse Friderichsen Syndrome Complicating Fulminant Enterobacter Cloacae Sepsis in a Preterm Infant: The Unresolved Issue of Corticosteroids

Bilateral adrenal hemorrhage can complicate severe sepsis in the neonate and is most commonly attributed to meningococcal disease; however, it can be caused by other etiologic agents as well. We report herein a fatal case of Enterobacter cloacae sepsis in a preterm infant, resulting in massive adrenal hemorrhages. This is the first documented case of adrenal hemorrhage following infection with this pathogen.

Adrenal apoplexy caused by fulminant sepsis in 20-year-old healthy male?: case report

Abstract Introduction. Bilateral massive adrenal hemorrhage (BMAH) is a rare catastrophic condition that manifests with acute adrenal insufficiency. Death can occur within a few hours or after many days. BMAH in association with fulminant septicemia and sepsis occurring in children and young adults is also known as the Waterhouse-Friderichsen syndrome. Fulminant sepsis associated with purpura is lethal in 40–70% of patients. Case report. The abrupt onset of fever with sore throat occurred in a 20-year old man. Next day in the early morning, he complained of severe symptoms: generalized weakness, shortness of breath and myalgia. Few hours later petechial rash occur. Within 30 hours from first symptoms he died in hospital. On autopsy, there were macroscopic bilateral areas of adrenal hemorrhage. Autopsy also revealed hemorrhage in almost all organs and tissues. Microbiological blood culture and toxicological finding was negative. Discussion. In our case, very high levels of procalcitonin and D-dimer, with all other clinically and autopsy findings, was directing medical examiners that a main cause of death was fulminant bacterial sepsis. Blood culture did not reveal any bacteria, so the cause of BMAH stays uncovered. The bacteria that most often cause fulminant sepsis connected with BMAH and death within 12–24 hours from first symptoms is N. meningitidis. It is very likely that N. meningitidis caused BMAH in our case, but it will stay in domain of speculation.

A fatal case of streptococcal and meningococcal meningitis in a 2-years-old child occurring as Waterhouse–Friderichsen Syndrome

We report a fatal case of streptococcal and meningococcal meningitis in a previously healthy 2-year-old child, a simultaneous co-infection of both pathogens that is poorly reported in the reviewed literature. The lack of a clinical diagnosis in addition to the medico-legal aspects arising from possible professional liability for the emergency service doctor who had failed to recognize the child's symptoms led to a forensic autopsy within 48 h after the death. After external and internal examination, Waterhouse–Friderichsen Syndrome (WFS) was suspected. Consequently, cerebrospinal fluid, whole blood, nasal and pharyngeal swab and pleural liquid samples were selected and collected for microbiological studies. All tested samples resulted Neisseria meningitidis DNA and Streptococcus pneumoniae DNA positive. The NM genotyping Real-Time PCR resulted positive for NM serotype C. Microscopic histological study confirmed these findings.We underline that when a patient presents fever and petechiae (50–60% of patients), WFS must be considered, even when the patient has a non-toxic appearance. Due to its rapid progression and often devastating consequences, therapy should be started as soon as WFS is suspected.Emphasis should also be placed on the importance of public education programs and on broadening protection against meningitis through new vaccines.In such cases, from a forensic point of view, there is a strong need for a robust, multidisciplinary approach in order to reach the correct post-mortem diagnosis.

Waterhouse-Friderichsen syndrome in an adult patient with meningococcal meningitis

Waterhouse-Friderichsen syndrome in an adult patient with meningococcal meningitis

CT画像所見からWaterhouse-Friderichsen症候群が疑われた乳児症例

発症後急速に悪化し，画像所見よりWaterhouse-Friderichisen症候群（Waterhouse-Friderichsen syndrome, WFS）が疑われた乳児症例を経験したので報告する。症例は6ヶ月，男児。意識障害にて救急搬送された。当初，経過と頭部CT所見から低酸素脳症と診断した。入室時より高カリウム血症，低血糖，代謝性アシドーシスを認め，ショックが遷延していたが，血行動態を安定させることができたため脳保護目的で低体温療法を開始した。入室8時間後より血行動態などが急激に悪化し，播種性血管内凝固症候群（disseminated intravascular coagulation, DIC）の所見を認めた。そこで感染症を強く疑い，低体温療法を中止し抗菌薬投与を開始した。感染源精査のため全身のCTを撮像したところ腹部CTにて両側の副腎出血を認め，WFSを疑いステロイド大量投与などの治療を行ったが，治療に反応することなく入室29時間後に死亡した。乳児の感染症へのアプローチ，低体温療法の適応などを考えさせられる症例であった。

A Case of Functional Asplenia and Pneumococcal Sepsis

Asplenia may refer to the spleen's surgical removal, functional impairment, or congenital absence. It is a risk factor for the development of severe bacterial infection. Functional asplenia is likely the most common presentation of this entity and has many etiologies. Those that are previously undiagnosed may present completely well until an episode of overt sepsis develops. The true incidence of mortality secondary to functional asplenia remains elusive. As lifetime mortality remains exceedingly high in the asplenic population regardless of etiology, markers of hyposplenism are important to detect. The present report describes an infant with trisomy 21 and previously undiagnosed functional asplenia who ultimately experienced overwhelming pneumococcal sepsis with features of Waterhouse-Friderichsen syndrome and died within 12 hours of initial presentation. It is a poignant reminder of what features to be cognizant of on peripheral blood smear in a previously well child, who may be at risk for a devastating consequence.

Waterhouse-friderichsen syndrome in an adult patient with meningococcal meningitis.

Waterhouse-Friderichsen syndrome is one of the fatal complications of meningococcal infection. Here we report a fatal case of this syndrome due to Neisseria meningitidis in a 29-year-old male patient who was admitted with high-grade fever and chills and vomiting since 7 days, a skin rash over the abdomen and trunk, and altered sensorium since 2 days. On examination, the signs of meningitis were present along with the hemorrhagic rash. The diagnosis of adrenal hemorrhage was confirmed by computerized tomographic scan findings. The patient was started on intravenous ceftriaxone, and the cerebrospinal fluid was processed for bacterial culture, which yielded growth of N meningitidis. The patient's condition deteriorated; he developed purpura along with a fall in platelet count, and died due to shock. This case is being reported as such a complication is comparatively rare in this antibiotic era, especially in adults, and starting steroids like dexamethasone prior to antibacterial therapy may be useful to diminish the inflammation brought about by bacterial cell death and thus help in reducing the otherwise high mortality in these cases.

Tributo ao centenário da Síndrome de Waterhouse-Friderichsen: relato de caso

The Waterhouse-Friderichsen Syndrome was first reported by Rupert Waterhouse exactly 100 years ago on March 4th, 1911. It is an acute infectious disease that generally progress to a lethal outcome despite the adoption of all available resources of an intensive therapy unit. We describe an illustrative case of meningococcal meningitis C. This report details the clinical, pathological and therapeutic features of a patient of 3 years and 4 months who had a fulminating evolution, despite adherence to updated recommendations for the treatment of pediatric septic shock. We stress the little change in clinical and pathological aspects of Waterhouse-Friderichsen Syndrome during the last 100 years, despite tremendous advances in therapy and technology of the pediatric intensive care.

Neisseria meningitidis induces platelet inhibition and increases vascular endothelial permeability via nitric oxide regulated pathways

Despite antibiotic therapy, infections with Neisseria meningitidis still demonstrate a high rate of morbidity and mortality even in developed countries. The fulminant septicaemic course, named Waterhouse-Friderichsen syndrome, with massive haemorrhage into the adrenal glands and widespread petechial bleeding suggest pathophysiological inhibition of platelet function. Our data show that N. meningitidis produces the important physiological platelet inhibitor and cardiovascular signalling molecule nitric oxide (NO), also known as endothelium-derived relaxing factor (EDRF). N. meningitidis -derived NO inhibited ADP-induced platelet aggregation through the activation of soluble guanylyl cyclase (sGC) followed by an increase in platelet cyclic nucleotide levels and subsequent activation of platelet cGMP- and cAMP- dependent protein kinases (PKG and PKA). Furthermore, direct measurement of horseradish peroxidase (HRP) passage through a vascular endothelial cell monolayer revealed that N. meningitidis significantly increased endothelial monolayer permeability. Immunfluorescence analysis demonstrated NO dependent disturbances in the structure of endothelial adherens junctions after co-incubation with N. meningitidis . In contrast to platelet inhibition, the NO effects on HBMEC were not mediated by cyclic nucleotides. Our study provides evidence that NO plays an essential role in the pathophysiology of septicaemic meningococcal infection.

Fatal Dog Bite in the Absence of Significant Trauma

Sudden and unexpected nontraumatic death in individuals with asplenia or hyposplenia is usually due to fulminant bacterial sepsis, most often involving Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae. We report a case of a previously well 40-year-old man who died 5 hours after hospital admission. At autopsy Waterhouse-Friderichsen syndrome was identified and Capnocytophaga canimorsus was subsequently isolated on antemortem blood cultures. Infection of humans with this organism is most often due to dog bite or contact. Upon specific inquiry it was ascertained that 2 days before admission the deceased had suffered a superficial bite to his hand by his pet Staffordshire Bullterrier dog. His relevant history included a previous splenectomy following blunt abdominal trauma. Asplenia and hyposplenia at autopsy should prompt microbiological testing with consideration of unusual organisms such as C. canimorsus. Although histories of animal contact or injury are often not available at the time of autopsy, this should also be considered in cases of apparent fulminant sepsis. In individuals with asplenia or hyposplenia, dog bites do not have to involve excessive tissue trauma, vascular compromise, or blood loss to be lethal.

Systemic Inflammatory Response Syndrome in Nonhuman Primates Culminating in Multiple Organ Failure, Acute Lung Injury, and Disseminated Intravascular Coagulation

The systemic inflammatory response syndrome (SIRS) is a clinicopathological manifestation of overexuberant acute-phase inflammation caused by infectious or noninfectious etiologies. The systemic release of pro-inflammatory cytokines, chemokines, and lipid and vasoactive mediators induces endothelial damage and microvascular thrombosis, potentially culminating in disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), and multiple organ dysfunction (MOD) or failure (MOF). We present five cases in the pig-tailed macaque and olive baboon where SIRS resulted in MOF, ARDS, DIC, and the Waterhouse-Friderichsen syndrome; each with gross and histological elements manifested as edema, deposition of fibrin, hemorrhage, and thrombosis. In the described cases, SIRS was the end-common pathway for multiple risk factors that parallel those documented in humans: major surgery, obstetric complications, and infection. The diagnosis of SIRS should be considered when evaluating nonhuman primate (NHP) cases of MOF manifesting with histological evidence of vascular leakage. Experimental manipulation of NHP models may be complicated by SIRS and accompanying rapid clinical decompensation. Such adverse events may compromise toxicological studies and should be avoided when possible.

Fatal pneumococcal Waterhouse-Friderichsen syndrome in a vaccinated adult with congenital asplenia

Fatal pneumococcal Waterhouse-Friderichsen syndrome in a vaccinated adult with congenital asplenia

Choque séptico puerperal por Streptococcus β-hemolítico e síndrome de Waterhouse-Friderichsen

An exceptional case of a 15-year-old puerpera with septic shock caused by Group A beta-hemolytic Streptococcus and Waterhouse-Friderichsen syndrome is reported. The findings were observed at the necropsy. The characteristics of the diagnosis, pathogenesis and evolution of this puerperal infection (sepsis), associated with adrenal hemorrhage and insufficiency are reviewed in this paper.