Waterhouse-Friderichsen Syndrome Research Articles

Waterhouse-Friderichsen syndrome complicating primary biliary sepsis due to Pasteurella multocida in a patient with cirrhosis.

Pasteurella multocida is an opportunistic pathogen causing bacteraemia in patients with liver dysfunction. A fulminant case of acute cholecystitis and septicaemia caused by P multocida, complicated by Waterhouse-Friderichsen syndrome without skin haemorrhage, is reported in a previously healthy 64 year old Chinese woman. The patient presented with a six hour history of sudden onset epigastric pain, vomiting, chills, and rigors. A presumptive diagnosis of cholangitis with septicaemic shock was made. Disease progression was rapid and the patient died within eight hours of symptom onset. This case is further proof that skin and mucosal haemorrhages are not an essential feature of Waterhouse-Friderichsen syndrome and this condition should be suspected in all patients presenting with sudden illness and fulminant septicaemia.

Melasma and acquired immunodeficiency syndrome (AIDS)

Background Hyperpigmentation of skin, mucous membranes and nails has been described in patients with acquired immune deficiency syndrome (AIDS).Patients and methods 7 AIDS patients affected with melasma-like facial hyperpigmentation were studied. The patients had human immunodeficiency virus infection associated with recurrent mucocutaneous and systemic opportunistic infections. All had a low T4-CD4 helper cell count and four of them died of severe infections, caused by cytomegalovirus (CMV), mycobacteria (Mycobacterium tuberculosis or Avium) and Pneumocystis carinii pneumonia. In these patients the autopsy showed intense infiltration of the adrenal glands. One of them died of Waterhouse-Friderichsen syndrome; her autopsy showed a massive presence of cytomegalovirus in the adrenal glands.Results In 4 patients dosages of testosterone, cortisol, T3, T4, TSH gave normal results. The level of DHEA-S was below normal revealing an adrenal insufficiency. The α-MSH test in 12 patients (4 patients with AIDS and facial hyperpigmentation and 8 volunteers with AIDS, but without pigmented facial lesions) revealed blood levels of α-MSH above the norm (60.33 pg/ml standard deviation 13.21). The α-MSH test in 20 healthy subjects revealed a mean value of 44.40 pg/ml (standard deviation 10.47). The biopsy of melasma revealed that melanocytes were present in normal numbers and size with a localized increase of melanin pigment in the basal cell layer.Conclusion An increased production of ACTH and its derivatives such as α-MSH pituitary may be the cause of hyperpigmentation in AIDS patients.

Bilateral massive adrenal hemorrhage

A systematic review of the etiopathogenesis of adrenal hemorrhage reveals that the factors that determine the occurrence of this complication in a patient can be identified prospectively. Such prospective diagnostic suspicion allows the significance of the otherwise nonspecific clinical features heralding this catastrophe to be appreciated in the precrisis interval. Confirmation of the diagnosis is achieved by visual demonstration of bilaterally enlarged and hyperdense adrenal glands on a CT scan and by demonstration of adrenocortical failure on hormonal evaluation. Preemptive steroid therapy and diagnostic evaluation during the precrisis period prevent the occurrence of a potentially disastrous adrenal crisis in a patient who is seriously ill from other problems and who cannot afford a setback of this severity. Because steroid therapy delayed until the stage of crisis may be unsuccessful in salvaging such a patient, prospective recognition must be based on identifying the patient at risk for BMAH and recognizing the significance of the nonspecific clinical features that accompany it in the appropriate clinical context.

Ｗａｔｅｒｈｏｕｓｅ‐Ｆｒｉｄｅｒｉｃｈｓｅｎ症候群を合併したひ摘後重症感染症の１症例

A case of “overwhelming postsplenectomy infection” is reported. The patient was a 34-year-old laborer who was splenectomized for trauma 5 years prior to the present illness. He went to work with a chill in the morning and came home with a high fever, vomiting and diarrhea at noon. Upon visiting an emergency center at 9p.m. that night, he was found to be in shock. In the ambulance on the way to our hospital, he became pulseless and unconscious. After a short period of stable blood pressure following CPR, he became hypotensive, and died the next morning. The initial examination showed that WBC, RBC and platelet counts were 8, 800, 520×104 and 1.7×104/mm3, respectively. Sepsis and DIG were suspected. Autopsy and blood culture revealed that the patient had developed pneumococcal sepsis and Waterhouse-Friderichsen syndrome. Immunochemical analysis showed that the amount of antibody to pneumococcal capsular polysaccharides had been reduced to a subnormal level. Splenectomized patients should be recognized as immunocompromized hosts and the high morbidity and mortality risk from sepsis in these patients should also be kept in mind.

Unilateral Spontaneous Adrenal Hemorrhage During ACTH Treatment of Multiple Sclerosis

Unilateral Spontaneous Adrenal Hemorrhage During ACTH Treatment of Multiple Sclerosis

Ｗａｔｅｒｈｏｕｓｅ‐Ｆｒｉｄｅｒｉｃｈｓｅｎ症候群例

A 52-year-old housewife with a chief complaint of vertigo and right tinnitus, suddenly fell into a coma 12 days after admission and died in 24 hours. Autopsy revealed massive hemorrhagic necrosis of both adrenal cortices, disseminated intravascular coagulation in various organs, and otic meningitis.These findings suggested the possibility that otic meningitis caused WaterhouseFriderichsen syndrome.The purpose of this case report is to describe Waterhouse-Friderichsen syndrome due to otic meningitis and to call attention to the early signs of impending neurotologic complications.

Deaths from meningococcal infection in Lanarkshire, 1984–1986

During the years 1984–1986, 81 cases of meningococcal infection occurred in Lanarkshire and 7 (8.6%) of them died. Almost all of those who died exhibited the Waterhouse-Friderichsen syndrome, Public anxiety is understandable. There is a need to emphasise the role of the specialist in community medicine when local outbreaks of meningitis occur so that the fears of the public may be allayed.

Intravasales Monitoring durch Arteria axillaris-Kanülierung im Säuglingsalter

In patients with respiratory failure and shock serial arterial blood analyses are important to calculate adequate respiratory therapy. During circulatory insufficiency punction of a radial artery can be difficult or impossible, especially in very young patients. The case report of a 9-month old female infant with septic shock and Waterhouse-Friderichsen's syndrome illustrates these problems and is helpful to describe an alternative technique. Percutaneous axillary arterial catheterization with a disposable venous cannula proved to be a simple and quick method to obtain the possibility of arterial monitoring in very young patients with severe hypotension.

Apparent Meningococcemia: Clinical Features of Disease Due to Haemophilus influenzae and Neisseria meningitidis

To determine the etiology of apparent meningococcemia, all cases of sepsis with coagulopathy, purpura, and/or adrenal hemorrhage (Waterhouse-Friderichsen syndrome) with and without shock occurring over a 12-year period were reviewed. A total of 42 cases were identified; 30 cases were caused by Neisseria meningitidis and 12 cases were caused by Haemophilus influenzae. Compared with patients with disease caused by H influenzae, patients with meningococcal disease were older, more often male, more often contracted the disease in winter-spring, and had a longer duration of antecedent symptoms; however, none of these differences was statistically significant. All patients were febrile (greater than 38 degrees C) and appeared toxic. Similar proportions in each group had shock and disseminated intravascular coagulopathy at the time of admission. Ten of 12 patients with H influenzae infection compared with 15/30 (P less than .05) with meningococcal infection were lethargic or comatose at the time of admission. Nine of 12 patients with H influenzae infection died compared with 5/30 with meningococcal disease (P less than .005); the mean time from onset of symptoms to death with H influenzae infection (20.7 +/- 11.4 [SE] hours) was significantly shorter (P less than .05) than with meningococcal infection (120 +/- 74.4 hours). Children with clinical signs of sepsis and with purpura, petechiae, or coagulopathy may have N meningitidis or H influenzae as etiologic agents. Initial antibiotic therapy should be directed against these pathogens.

Adrenal, cutaneous and myocardial lesions in fulminating endotoxinemia: (Waterhouse-Friderichsen Syndrome)

Summary Waterhouse-Friderichsen syndrome (WFS) was diagnosed in ten autopsy cases (6 to 16 years of age) according to the following criteria: 1. fulminating meningococcic septicemia, 2. massive cutaneous hemorrhages, and 3. bilateral hemorrhagic necrosis of the adrenals. Only one case showed disseminated intravascular coagulation (DIC) and hemorrhagic diathesis. Skin histology revealed small numbers of microthrombi to be present in all cases. The vital organs, however, did not all disclose such microthrombi: only 3 adrenal, 4 kidney, and 2 lung specimens presented microthrombi. The hearts showed no evidence of DIC, but did reveal histological signs of myocarditis accompanied by endothelial damage, interstitial edema, fibrinous transudation, granulocytic infiltration, hemorrhages, and foci of necrotic heart muscle fibers. These findings suggest a toxic (endotoxinogenic) damage of the endothelial cells, vascular walls and adjacent interstitial and parenchymal tissues. The hemorrhagic necroses observed in the adrenal and the hemorrhagic skin lesions, likewise, appear to be the result of direct endotoxinic damage, rather than microcirculatory ischemia resulting from microthrombi. Thus, we believe that overwhelming toxemia plays the immediate and dicisive role in the fatal outcome of WFS. Adrenal failure and systemic shock with DIC merely present additional complications which may or may not be present. In all ten cases investigated, interstitial myocarditis was found; this and other supportive clinical and morphological findings point heavily to cardiac arrest as the immediate cause of death in fatal WFS.

Clinicopathologic characteristics of septicemia in sickle cell disease.

Bacterial septicemia occurred in 22 of 210 pediatric patients with sickle cell disease over a nine-year period, an attack rate of 10.5%. Children less than 2 1/2 years old with hemoglobin SS were at greatest risk; Streptococcus pneumoniae was the most common pathogen. Although sudden febrile illness developed in nine patients, in 13 a gradual prodrome was associated with symptoms for more than 24 hours before evaluation. Both initial body temperature and WBC count were highly variable. In all six fatal cases, autopsy disclosed adrenal hemorrhagic necrosis, which in three was diffuse and typical of that seen in the Waterhouse-Friderichsen syndrome. Recommendations in patients with sickle cell disease and fever, even if only of moderate degree, include the rapid initiation of antibiotic therapy and the use of corticosteroids at the first sign of circulatory insufficiency.

Fulminant Meningococcemia After Splenectomy

FULMINANT bacterial infections complicated by shock and disseminated intravascular coagulation have been reported after splenectomy for trauma.^1-3The majority of these infections are caused by bacteria with polysaccharide capsules; pneumococci are demonstrated in half of the cases.⁴We report two cases of atypical Waterhouse-Friderichsen syndrome from meningococcemia in asplenic young women who did not manifest skin lesions. <h3>Report of Cases</h3><h3>Case 1.—</h3> A 17-year-old girl came to a small hospital emergency room with a one-day history of fever. Malaise and transient blurred vision were noted. About eight hours previously her roommate noted her to be confused. Medical history included a splenectomy after abdominal trauma at age 13 years. She was cyanotic and unresponsive in the emergency room. No skin lesions were present. Shortly after arrival she had a cardiac arrest, and resuscitation measures were unsuccessful. Autopsy showed purulent meningitis, splenosis, and scleral, pulmonary, and bilateral adrenal hemorrhage. Typing

The Shwartzman reaction: a review including clinical manifestations and proposal for a univisceral or single organ third type.

The Shwartzman reaction was first described more than 50 years ago and two types, the generalized and the localized, were established in the early 1930s. Studies were mostly related to experimental pathology or immunology, and its significance in clinical medicine was initially obscure though thought to be obstetrically relevant. It is thought that the generalized type has a relation to human disease and that disseminated intravascular coagulation in man is really the counterpart of the generalized Shwartzman reaction in animals. The localized type on the other hand does not have obvious practical clinical pathological significance and tumor necrosis may be the only real example which is commonly seen. Further studies on the Shwartzman reaction relevant to human pathology have, however, suggested that it could be applied to several diseases, the pathogenesis of which was still obscure. The significance seems, however, different from either the generalized or localized type of reaction and so a proposal of the incidence of a third type--'univisceral' or 'single organ' Shwartzman reaction is made. Acute liver necrosis, Waterhouse-Friderichsen's syndrome, haemolytic uraemic anemia, idiopathic pulmonary haemorrhage, acute pancreatitis, acute pituitary necrosis and pseudomembranous colitis all seem to have features suggesting that they could be clinical manifestations of this type of Shwartzman reaction with focal intravascular coagulation.

Waterhouse-Friderichsen syndrome caused by Haemophilus influenzae type b.

Waterhouse-Friderichsen syndrome caused by Haemophilus influenzae type b.

Adrenal lesions in calves dying from endotoxin shock, with special reference to the Waterhouse-Friderichsen syndrome

The adrenals of 46 calves with bacterial shock (septicaemia and diarrhoea with Gram-negative bacteria) were examined histologically. In 2 animals, total necrosis of the whole adrenals or the adrenal cortices, combined with thrombi and haemorrhages, was found bilaterally. These cases are exact counterparts of the Waterhouse-Friderichsen syndrome in man. In 35 further animals small areas of focal necrosis and microthrombi could be demonstrated histologically. No changes were observed in the adrenal glands of the remaining 9 calves.

Relations between Activation and Inhibition of Fibrinolysis in the Walls of Human Arteries and Veins

From systematic studies of both the activation and the inhibition of fibrinolysis in human blood vessels, data which provided insight into the fibrinolysis antagonism along and across the human vessel wall were obtained. The capacity for fibrinolysis initiated by plasminogen activator in sections of human arteries and veins as demonstrated by the fibrin slide technique differed greatly along and across the vessel walls. Inhibition of plasmin fibrinolysis in these blood vessels as detected by the fibrin slide sandwich technique was present at sites of low fibrinolytic activity, while inhibition was absent in areas showing strong fibrinolysis. Fibrinolysis was related to endothelial cells, while inhibition of fibrinolysis was brought about by smooth muscle cells. The results indicate that differences in endothelial fibrinolysis may be the result of differences in inhibition of fibrinolysis caused by variations in the number of smooth muscle cells present locally. A systemic decrease in endothelial fibrinolysis observed in endotoxin shock, hyaline membrane disease and a Waterhouse-Friderichsen syndrome appeared to be associated with a systemic increase in inhibition of fibrinolysis not related to smooth muscle cells.

Localization and distribution of fibrinolysis inhibition in the walls of human arteries and veins

A systematic study on the location and intensity of fibrinolysis inhibition in human arteries and veins by the use of a standardized fibrin slide sandwich technique yielded data for an overall comparison of fibrinolysis inhibition along and across the human vessel wall. Arteries generally showed marked plasmin inhibition in the intimal and medial layers, but little inhibition in the adventitia. The external layer of loose connective tissue in the veins generally showed no plasmin inhibition. Plasmin inhibition was usually present in the combined intimal/medial/adventitial layer of the veins, but inhibition in these layers varied greatly according to the location of the vein in the body. Veins situated in the lower parts of the body exhibited more plasmin inhibition than veins at the upper levels. Inhibition of plasmin was found to be related to the presence of smooth muscle cells. However, in endotoxin shock, hyaline membrane disease and a case of Waterhouse-Friderichsen syndrome, additional plasmin inhibition was observed in vascular areas of loose connective tissue free from smooth muscle cells. Selective inhibition of urokinase-induced fibrinolysis was observed only in the connective tissue around the vessels of the human umbilical cord.

Distribution and variation of fibrinolytic activity in the walls of human arteries and veins.

A systematic study on the location and intensity of the fibrinolytic activity in more than 500 samples of human arteries and veins from 50 routine necropsies and 35 blood vessel biopsies was performed. Data were obtained for an overall comparison of the fibrinolytic activity along and across the walls of human blood vessels by the use of a standardized fibrin slide technique. Arteries generally showed little or no fibrinolytic activity in the intima and media but strong activity in the adventitia. Veins showed a comparable strong fibrinolytic activity in the external layer of loose connective tissue. Fibrinolytic activity in the venous intima, media and adventitia was generally weaker but varied greatly according to position in the body. Veins situated in the lower parts of the body had less fibrinolytic activity than the veins at the upper levels. Fibrinolytic activity was found to be related to the endothelium of the vasa vasorum and/or of the main lumen of the vascular wall. Increased fibrinolytic activity was observed in arteries and veins in cases of sudden death, vasogenic shock, cerebral hemorrhage and cirrhosis. Decreased fibrinolytic activity was encountered in blood vessels in cases of endotoxin shock, hyaline membrane disease and a case of Waterhouse-Friderichsen syndrome.

The Waterhouse-Friderichsen Syndrome and its Orthopaedic Consequences

AbstractTwo cases of fulminating meningococcal septicaemia with Waterhouse-Friderichsen syndrome are reported in young servicemen. Both were complicated by peripheral gangrene of unusual severity, which required the modification of standard surgical procedures to meet their individual requirements. The rationale of management is discussed in the light of the pathological processes involved, and views are advanced on the place of steroids and heparin in the acute stage.

Disseminated intravascular coagulation and the Waterhouse-Friderichsen syndrome.

In a clinico-pathological study of 13 children who died with Waterhouse-Friderichsen syndrome, there were deposits of fibrin in many organs, especially the adrenal glands and the kidneys. This finding supports the hypothesis that disseminated intravascular coagulation (DIC) occurs in this syndrome. The exact role that DIC plays has not been defined; though it probably contributes to the severe shock and the widespread haemorrhages; the adrenal haemorrhages appear not to be due directly to DIC. The presence of DIC in the Waterhouse-Friderichsen syndrome suggests that heparin should be a logical form of treatment.