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.

Introduction

Despite the advent of new microbials, meningococcal infection remains a leading cause of morbidity and mortality.[1-4] Based on the sequence of pathophysiological events and the agent and host factors, a wide spectrum of presentations may be seen. Patients with invasive meningococcal disease can present with meningitis alone or meningitis with shock.[1-4]

The Waterhouse Friderichsen syndrome is a severe complication of meningococcal infection.[1-3] The patient presents with meningococcal disease along with shock due to adrenal hemorrhage.[1-4] Here we report a fatal case of Waterhouse-Friedrichsen syndrome in an adult male patient with meningococcal disease.

Case Report

A 29-year-old male patient was admitted with a history of high-grade fever with chills and vomiting of 7 days’ duration, along with skin rash over the abdomen and trunk for the last 2 days. After admission he developed a hemorrhagic rash. There was no significant finding noted in the family history or the past history. On examination, his general condition was unstable and cyanosis was present. He was febrile, with a pulse rate of 90/min and systolic BP of 70 mm Hg. The neurological examination showed that the Kerning and Brudzinski signs were positive. A rash was observed over the whole of the body, but it was predominantly over the abdomen and trunk [Figure 1]. The cerebrospinal fluid (CSF) tapped was collected under aseptic precautions and was processed according to standard bacteriological procedures. Routine microscopy of the CSF showed a cell count of 9400/mm3, with 86% polymorphs and 14% lymphocytes. The CSF protein was raised to 309 mg% and the sugar was reduced to 20 mg%. The Gram stained smear of the CSF showed pus cells along with gram-negative diplococci, some of which were intracellular and some extracellular [Figure 2]. The CSF was cultured on chocolate agar, blood agar, and MacConkey agar and the media were incubated at 37°C in humid conditions in a candle jar. After overnight incubation, tiny translucent colonies were observed on chocolate agar and blood agar, which was later identified by standard laboratory procedures to be that of Neisseria meningitidis. CT scan confirmed adrenal hemorrhage, which is supposed to be a diagnostic factor for Waterhouse-Friderichsen syndrome. Antibiotic sensitivity tests showed that the isolate was sensitive to all the antibiotics tested, i.e., ceftriaxone, chloramphenicol, penicillin, and trimethoprim + sulfamethoxazole. The patient meanwhile was started on ceftriaxone and steroids, but he went into shock and expired on the third day after admission.

Figure 1

Purpuric, hemorrhagic skin lesions associated with the Waterhouse-Friedrichsen syndrome

Figure 2

Gram stained smear showing pus cells along with gram-negative diplococci

This case is being reported as Waterhouse-Friderichsen syndrome is comparatively rare in this antibiotic era, especially in adults. If early diagnosis and antibacterial treatment, along with steroids, is not administered then there is high associated mortality.

Discussion

Asia has been the focus of meningococcal meningitis. Many outbreaks of meningococcal meningitis were documented during 1966 and 1985 in Delhi and adjoining areas.[5] in early 2005, a spurt in the number of cases of meningococcemia and meningitis due to N meningitidis was reported from India. Upto June 2005, 429 cases were reported. The majority of the cases, and all the deaths, occurred in young adults between 16–30 years of age.[25]

Skin hemorrhages are hallmark of invasive meningococcal disease. Microscopically, these lesions are characterized by endothelial damage, which leads to hemorrhages, and microthrombi in small vessels. This is consistent with a generalized Sanarelli-Shwartzman reaction. The lesions are the result of endotoxins- and cytokine-primed vasculitis that is mediated by the upregulation of adhesion molecules on endothelium and degranulation activated neutrophils. Massive adrenal hemorrhage (Waterhouse-Friderichsen syndrome)[1] is an uncommon, but usually fatal, consequence of overwhelming sepsis.[6] Although disseminated intravascular coagulation is a generalized phenomenon, it may affect any organ and when it causes adrenal hemorrhages the condition is called Waterhouse-Friderichsen syndrome. Gram's staining of the CSF is still considered an important method for rapid diagnosis, but culture from CSF or skin lesion biopsy is the gold standard.[1-6] In some cases, blood culture may yield the organism. In the present case only CSF was processed, which showed growth of N meningitidis. In India, there is a paucity of studies on antimicrobial susceptibility of N meningitidis. Most of the studies showed that the isolates were sensitive to penicillin, ampicillin, and ceftriaxone; in two-thirds of the cases the isolates were resistant to ciprofloxacin.[25] Our isolate was sensitive to all the drugs tested, but the patient expired despite adequate antibiotic therapy, probably due to the adrenal hemorrhage leading to shock.

Waterhouse-Friderichsen syndrome, first reported in 1911 by Rubert Waterhouse, is characterized by fever, rash, purpura, coagulopathy, and shock.[4] It has been suggested by many authors that this syndrome is more common than what literature reports indicate, many cases probably being missed due to lack of familiarity with the condition. The majority of the diseases caused by meningococci occur in children under 2 years of age, but it can occur at any age.[7] Though Waterhouse-Friderichsen syndrome is common with N meningitidis, other organisms are also associated with this syndrome, including Streptococcus pneumoniae, β-hemolytic streptococcus group A, Staphylococcus aureus, Neisseria gonorrhoeae, Escherichia coli, Hemophilus influenzae, Klebsiella sp, and Pasturella sp. Although the condition is predominantly associated with meningococcal infection and with sepsis due to other organisms, there are also noninfectious causes of the Waterhouse-Friderichsen syndrome, such as anticoagulant treatment, antiphospholipid syndrome, trauma, and postoperative adrenal hemorrhages.[78]

Though N meningitidis is susceptible to the commonly used antibiotics, the mortality in Waterhouse-Friderichsen syndrome is approximately 20%, rising to 50% if the patient is in shock as happened in the present case[9].

If there are any signs and symptoms suggestive of Waterhouse-Friderichsen syndrome then 100 mg of hydrocortisone should also be given to the patient. If possible it should be given intravenously, but if a vein is not accessible the intramuscular route will suffice. Studied have shown that even prophylactically administered steroid can be life saving. Starting steroids like dexamethasone prior to antibacterial therapy may be useful to diminish the meningococcal inflammation brought about by bacterial cell death.[6] Thus early diagnosis and proper treatment is necessary to prevent death from this otherwise fatal condition.