Case Report

Chronic meningococcaemia

Ben Teoh and Aled Williams

Emergency Department, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia

Emergency Medicine (2000) 12, 151–154

Dr Ben Teoh, The Cancer Foundation Cottage Hospice, Shenton Park, WA 6008, Australia. Email: enhardgainsteoh@hotmail.com

Ben Teoh, MB, BS, Registrar; Aled Williams, MBChB, MRCGP, FACEM, Staff Specialist, Emergency Medicine.

Case history

A 14-year-old Caucasian male presented with a 10-dayhistory of intermittent fever and chills, malaise, mildfrontal headache, sore throat and a non-productivecough. On day three he developed generalized myalgia,arthralgia of the metacarpophalangeal joints andknees and swelling of the right knee. On day seven hewoke to find a ‘red, spotty rash’ on his trunk and limbs.He denied nausea, vomiting or photophobia. There wasno past medical history of note. In particular, therewas no history of rheumatic fever, i.v. drug use, recenttravel, insect bites or sexual intercourse. Family historywas unremarkable. Paracetamol was the only currentmedication.

Physical examination revealed an alert, mildlyflushed but not unwell-looking male. Pulse rate was84/min, respiratory rate 16/min, blood pressure120/80 mmHg and temperature 38.7°C. There was no

jaundice, lymphadenopathy or splinter haemorrhagesand no signs of meningism. A few petechiae werepresent on the soft palate, but there was no pharyngitisor otitis noted. A small effusion of the right knee jointwas evident. The right knee and themetacarpophalangeal joints were mildly tender onpalpation.

A petechial rash was present on the extensorsurfaces of the limbs, anterior trunk, the palms, solesand hard palate. The pharynx was mildlyerythematous.

Investigations revealed a haemoglobin (Hb) of14.2 g/dL (normal range (NR), 11.3–15.5 g/dL),white cell count (WCC) of 15.6 3 109/L (NR,4.02–11.0 3 109/L) with a neutrophilia of 13.7 3 109/L(NR, 1.8–7.5 3 109/L) and a platelet count of126 3 109/L (NR, 150–400 3 109/L). Urea, creatinineand electrolytes were within normal limits andurinalysis was unremarkable.

Abstract

Meningococcal infection usually presents as a severe illness with septicaemia,cardiovascular collapse and a purpuric rash. Less commonly, it presents in a chronic formwith an intermittent course over a number of weeks. Chronic meningococcaemia maymimic other conditions, such as viral illness or autoimmune disease. Early diagnosis ofchronic meningococcaemia is essential because it may progress into the more familiaracute form. Emergency physicians need to be aware of the disease and its clinical featuresso that appropriate interventions can be made when a patient presents with a suggestiveclinical picture. In this article, we present a case of chronic meningococcaemia that wasseen three times in an emergency department before the correct diagnosis was made. Wewill also review the pathophysiology and the clinical features that may aid in the earlydiagnosis of this unusual condition.

Key words: chronic meningococcaemia, meningococcal infection.

septicemia in which there is a febrile period of at leastone week, without signs or symptoms of meningism,and whose clinical course changes abruptly ifmeningitis supervenes.’3

The true incidence of CM is unknown but it isthought to be rare and reports are becomingincreasingly uncommon. In 1963, Benoit reviewed 148cases of CM.4 Age incidence ranged from 3 months to62 years, with a mean age of 26.5 years. Sex incidencewas approximately equal (if one excludes the skeweddistribution caused by the large proportion ofservicemen in Benoit’s series). The majority of caseswere previously healthy.

Pathophysiology

The clinical course of a patient with CM is verydifferent to what is usually seen with meningococcalinfection. Differences in clinical manifestations of aninfectious agent are attributable to changes in theagent’s virulence, change in the response of the host ora combination of these factors. Benoit hypothesizedthat, in CM, a defective host response was the majorfactor.4 More recent work has suggested that theimmune system deficiency may lie in the terminalcomponents of the complement pathway.5 Otherdeficiencies implicated include hypoimmunoglobulin-aemia, properdin deficiency and impaired complement-mediated monocyte lysis of meningococci.6

The vascular collapse characteristic of acutemeningococcaemia is thought to be due to complementactivation. Late complement component deficiency mayresult in a reduced inflammatory response, producingless tissue damage and no vascular collapse. Normaldevelopment of protective antibody facilitatesadequate opsonization and phagocytosis. Thisproduces containment, but not elimination of themeningococcus, possibly explaining the more chronic,indolent course.7

The balance between infectious agent and hostimmune system can change at any stage in the courseof the illness. Jennens et al. report a case in whichprednisolone, administered to treat a presumeddiagnosis of autoimmune vasculitis, precipitatedfulminant progression of meningococcaemia.8

Similarly, it is thought that antibiotics administered fora presumed diagnosis of viral illness may tip thebalance in favour of the host. Increased use ofantibiotics for viral-type symptoms may explain theapparent decrease in incidence of CM.6

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A provisional diagnosis was made of a viral illnesswith a vasculitic rash. The patient was dischargedhome but asked to return the next day for a repeat fullblood count (FBC) in view of the mildthrombocytopenia. On review the next day, thepatient’s signs and symptoms were unchanged. HisWCC was 12.7 3 109/L (neutrophilia 9.91 3 109/L) andhis platelet count was 128 3 109/L. His urea, creatinine,electrolytes and urinalysis remained unremarkable. Hewas discharged for general practitioner (GP) follow up.

Two days later the patient returned because ofconcern that he was not improving. The patient’ssymptoms and signs remained unchanged. Investi-gations revealed a WCC of 13.8 3 109/L (neutrophilia11.4 3 109/L), Hb of 12.9 g/dL and platelets of88 3 109/L. Urea, creatinine, electrolytes, total protein,albumin, calcium, bilirubin, alkaline phosphatase andalanine transferase were all within normal range.Erythrocyte sedimentation rate (ESR) and C-reativeprotein (CRP) were elevated at 68 and 254, respectively.A mid-stream urine sample showed no abnormality.His chest X-ray was normal.

The patient was admitted to a ward where his feverpeaked at 39.4°C and arthralgias persisted. Aspirate ofhis right knee revealed a reactive inflammation with100 000 white cells/uL. No organisms were present onmicroscopy or culture. Urine polymerase chain reactionfor Neisseria gonorrhoeae and Chlamydia trachomatiswas negative. On the second day of admission, bloodcultures grew Neisseria meningitidis type B, sensitiveto ceftriaxone, penicillin, ciprofloxacin and rifampicin.Ceftriaxone 2 g i.v. daily was commenced and on thesecond day of treatment the patient symptomaticallyimproved, became afebrile and the rash began to fade.After 5 days of treatment the patient was discharged,afebrile and asymptomatic. A further 2 days of i.v.ceftriaxone was to be administered by his GP. Thepatient’s only close contact, his mother, was given acourse of rifampicin. Elimination of nasopharyngealcarriage in the patient was achieved by his ceftriaxonetherapy.1

The patient was reviewed by his GP and remainedwell.

Discussion

The clinical features of chronic meningococcaemia(CM) were first described in 1902 by Saloman.2 In 1924,Dock defined CM as ‘…those cases of meningococcal

thrombocytopenia were rare. Death occurred in 10%,the majority attributed to carditis.4

Diagnosis

The diagnosis of CM should be considered in patientswho present with a suggestive clinical picture.Definitive diagnosis is made on blood culture growth ofN. meningitidis. Multiple blood cultures may berequired to isolate the organism.

Most patients have white cell counts < 20 3 109/L.Both ESR and CRP are usually raised. Blood glucose,urea and electrolytes and coagulation profiles arewithin normal limits. Occasionally, there may be a mildthrombocytopenia.4

Electrocardiogram and chest X-ray are usuallynormal. Cultures or Gram stain identification from skinlesions are rarely positive.4 A lumbar puncture toexclude meningeal involvement is indicated if anyclinical suspicion exists.

Differential diagnosis The clinical presentation of fever, rash and jointsymptoms has an extensive differential diagnosis. Thisis summarized (Table 2).

Treatment

Once the diagnosis of CM is made, the treatment ofchoice is ceftriaxone 2 g daily i.v. for 7 days. Withprompt treatment the symptoms soon resolve.

Close contacts should be given prophylaxis withrifampicin or ciprofloxacin.12

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Chronic meningococcaemia

Clinical course

Chronic meningococcaemia typically presents withintermittent or continuous fever followed by a rash,arthralgia, myalgia and symptoms of upperrespiratory tract infection. Systemic debility is usuallyslight. Afebrile periods may range from 1 to 10 days.Patients are often well between febrile episodes. Theclinical features of CM are summarized (Table 1).

The rash of CM is commonly maculopapular, incontrast to the petechial or purpuric rash seen in acutemeningococcaemia. The rash may also appear nodular,petechial or polymorphous. The distribution is usuallyconfined to the extensor surfaces of limbs and anteriortrunk with facial sparing. Microscopically, the rash ischaracterized by a perivascular mononuclear cellinfiltrate resembling an allergic leucocytoclasticvasculitis.8 The necrosis and thrombosis seen in acutemeningococcaemia are not features. Skin biopsy rarelyreveals diplococci.9,10 Similarly, in joint effusion fluid,the meningococcus is rarely seen or cultured. Thelikely pathogenesis of the skin and joint manifestationsis immune complex deposition and subsequentinflammatory pathway activation.11

Without treatment, symptoms of CM may persistfor months. The most feared complication isprogression to acute meningitis, which occurred in15% of Benoit’s cases.4 In Benoit’s series, othercomplications which were defined as ‘localization ofinfection’ included: carditis (12.8%), anaemia (10.8%)and nephritis (6.8%). Epididymitis, retinitis, iritis and

Table 1. Clinical features of chronic meningococcaemia

Feature No. patients (%)

FeverIntermittent 70Continuous 30

Rash 93Joint complaints 70Headache 61URTI 37Splenomegaly 13.5Weight loss 9

URTI, Upper respiratory tract infection.

Table 2. Differential diagnosis of chronic meningococcaemia

1. Bacterial1.1 Rheumatic fever1.2 Scalded skin syndrome1.3 Subacute bacterial endocarditis1.4 Neisseria gonococcaemia1.5 Typhoid fever

2. Collagen vascular disease3. Henoch–Schönlein purpura4. Immunological

4.1 Erythema multiforme4.2 Erythema nodosum

5. Viral5.1 Enterovirus

6. Still’s disease

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2. Saloman H. Uber Meningokokkenseptikamie. Klin. Wochenschr.1902, 39: 1045–8.

3. Dock W. Intermittent fever of several months duration due tomeningococcemia. JAMA 1924, 83: 81.

4. Benoit FL. Chronic meningococcemia: Case report and review ofthe literature Am. J. Med. 1963, 35: 103–12.

5. Clough J, Clough M, Weinstein A et al. Familial late complementcomponent deficiency with chronic meningococcemia. Arch.Intern. Med. 1980; 140: 929–33.

6. Nielsen EH. Complement and immunoglobulin studies in 15cases of chronic meningococcemia: Properdin deficiency andhypoimmunoglobulinemia. Scand. J. Infect. Dis. 1990: 22: 31–6.

7. Rosen MS. Chronic Meningococcal meningitis: An associationwith C5 deficiency. Arch. Intern. Med. 1998; 148: 1441–2.

8. Jennens ID, O’Reilly M, Yung A. Chronic meningococcemia Med.J. Aust. 1990; 153: 556–9.

9. Tuso PJ, Ahern MJ. Chronic meningococcemia. Conn. Med. 1987,51: 698–702.

10. Angoff G. A case of chronic meningococcemia with unusualfeatures. Am. J. Med. Sci. 1975, 269: 243–6.

11. Schaad UB. Arthritis in disease due to N. meningitidis. Rev.Infect. Dis. 1980; 2: 880–8.

12. Harvey K, Beavis M, Christiansen K. Therapeutic Guidelines:Antibiotics, 10th edn. Melbourne: Therapeutic Guidelines, 1999;37–42.

Summary

Chronic meningococcaemia is a rare form of infectioncaused by N. meningitidis. The clinical picture of fever,rash and arthralgia over the course of several weeksmay result in a misdiagnosis of autoimmune disease orviral illness. The consequences of this can bedisastrous because deterioration into acute meningitismay occur at any stage. Emergency physicians shouldbe aware of the diagnosis and should consider it inpatients presenting with a suggestive clinical picture.Admission of the patient for further investigation andtreatment may be required.

Accepted 17 January 2000

References

1. Judson FN. Single dose ceftriaxone to eradicate pharyngeal N.meningitidis. Lancet 1984; 2: 1462–3.