J Clin Pathol: first published as 10.1136/jcp.21.4.437 on 1 July 1968. Downloaded from

J. clin. Path. (1968), 21, 437-439

Septicaemia caused by flavescens

PAUL T. WERTLAKE1 AND TEMPLE W. WILLIAMS Jr2 From the U.S. Department of Health, Education and Welfare, Public Health Service, National Institutes of Health, Clinical Pathology Department, Clinical Center and Laboratory of Clinical Investigations, National Institute of Allergy and Infectious Disease, Bethesda, Maryland, U.S.A.

SYNOPSIS Septicaemia caused byN.flavescens is reported for the first time. The septicaemia developed following dental surgery, and the clinical picture was indistinguishable from that of chronic meningo- coccaemia. The skin lesions resembled the cutaneous manifestations of gonococcaemia. The patient responded to treatment with sulphonamides and with no relapse over 18 months of follow-up.

Neisseria flavescens is a member of the chromo- shortly after admission developed chills and fever (40°C). genic, usually non-pathogenic group of neisseria. She specifically denied recent insect bites, drug ingestion, As such, it is ordinarily a saprophyte of the mouth, or consumption of contaminated foods. She denied nasopharynx, and upper respiratory tree. Whereas sexual contacts, exposure to sick children or adults, and there was no history of surgical or gynaecological mani- other members of the chromogenic neisseria have pulations other than the dental procedure one week been reported as the causative agents of endo- before the onset of the illness. carditis, and N. flavescens has been implicated as Physical examination showed a white woman appearing the causative agent in , it has not been acutely ill rather than chronically ill. Temperature was previously reported as a cause of bacteraemia. 40°C, and the pulse rate was 110/min. There were numer- http://jcp.bmj.com/ The following report presents a case of N. flavescens ous erythematous maculo-papular, papulo-nodular and septicaemia resembling meningococcaemia. pustular skin lesions over the extensor surfaces of the distal surfaces of the limbs, and a smaller number over the trunk, back, and buccal mucosa. Several lesions on CASE REPORT the extremities had necrotic centres. The right third metacarpophalangeal joint was red, The patient (CC No. 05-15-81), a 20-year-old white hot, swollen and tender. Large joints, including knees woman, was well until seven days after dental surgery and elbows, were normal. There were no lesions visible on September 24, 2021 by guest. Protected copyright. (endodontics) when she developed chills, fever, headache, in the ocular fundi. The teeth and gums were in good nausea, and vomiting. The febrile illness lasted only six repair although there was heavy tartar on the clinical to 12 hours, and she was treated with antiemetics but crown. There was no sign of infection at the site of the no antibiotics. During the following 14 days, however, recent surgery. Heart sounds were normal with no she had three similar bouts of transient fever with chills, murmurs. Liver and spleen were not palpable. Pelvic headache, myalgia, arthralgias, nausea, and occasional examination was within normal limits. The neurological vomiting. The third such episode was accompanied by a examination was unremarkable. rash over the extremities, and local heat and erythema Laboratory data at the time of admission demon- with pain and tenderness in two metacarpophalangeal strated 12,700 leucocytes per cu mm with a shift to the joints of the right hand. The fever was transient, lasting left. Haemoglobin, platelet count, urine analysis, blood only six to eight hours, but the rash persisted. urea nitrogen, blood glucose, serum sodium, potassium, On the fourteenth day following the onset of symptoms and chloride concentrations and carbon dioxide content the patient was admitted to the Clinical Center, and were normal. Alkaline phosphatase, serum glutamic oxalacetic and pyruvic transaminase, thymol turbidity, 'Present Address: The Clinical Laboratory Medical Group,679 S. total serum protein, and serum protein electrophoresis Westlake Ave, Los Angeles, Calif. 90057 values were normal. Serological studies employing specific agglutinins did 'Present Address: Baylor University Medical School, Houston, 77025 not demonstrate any significant increase of agglutinins Texas for Salmonella group A. B, C, D, typhoid H, Proteus Received for publication 25 October 1967. OX19, and Brucella abortus. The heterophile antibody 437 J Clin Pathol: first published as 10.1136/jcp.21.4.437 on 1 July 1968. Downloaded from

438 Paul T. Wertlake and Temple W. Williams Jr and antistreptolysin 0 titres were not significantly as an isolate from the cerebrospinal fluid of 14 cases raised. The C-reactive protein test was strongly positive. of meningitis occurring during a single epidemic in Two lupus erythematosus cell preparations and the bento- Chicago in 1928. Subsequently this organism has nite flocculation test were negative. Complement-fixation been reported as the aetiological agent in four other tests for fungi as well as skin tests for fungi and an intermediate strength PPD test were negative. The electro- cases of meningitis (Prentice, 1957; Noguchi, cardiogram and radiographs of the chest and abdomen Nachum, and Lawrence, 1963; Ruiz Sanchez, F., were normal. X-ray examination of the hands revealed Ruiz Sanchez, A., Negrete, and Rodriguez, 1963). a soft tissue swelling about the third metacarpophalangeal Except for the present case no other reports of joint on the right. septicaemia caused by this agent are known. Lumbar puncture showed clear cerebrospinal fluid The chromogenic neisseria include N. flavescens, under an opening pressure of 140 mm H20. The cere- N. subflava, N. flava, N. perflava, and N. caviae. brospinal fluid contained 2 lymphocytes/mm3, 75% The habitat of all but N. caviae is the mucous mem- glucose, and 26 mg% protein. Culture was negative. branes of the respiratory tract of man. The habitat A swab from the os of the cervix cultured gamma streptococci, Proteus sp. and Staphylococcus albus. A of N. caviae is the pharynx of animals. The chromo- throat swab yielded alpha streptococci, gamma strepto- genicity of these organisms is characteristic on cocci, haemolytic Staphylococcus aureus, deoxyribonu- Leoffler's serum medium. Greenish-yellow chromo- clease positive, and a Neisseria sp. which was discarded genesis is typical of the chromogenic neisseria without additional identification. Culture of urine was occurring in man. Differentiation of the various negative and two stools were negative for pathogenic chromogenic neisseria may be made by sugar . fermentation. N. flavescens produces no acid from Blood cultures, taken hourly for four hours after glucose, fructose, maltose, or sucrose. The other admission, all yielded a Gram-negative . chromogenic neisseria of man produce acid from A stained smear of material from a pustular skin lesion fructose and N. flava acid from sucrose. The organ- revealed Gram-negative cocci, although cultures were negative. ism recovered in the present case was distinguished The organism isolated from the blood cultures grew from N. meningitidis by its pigment production and at 22°C and 37°C on nutrient media in atmospheric failure to produce acid from glucose or maltose. conditions as well as in an environment of increased N. meningitidis colonies are non-pigmented and C0. Growth was obtained from all five blood cultures produce acid from both glucose and maltose fer- each of which consisted of approximately 12 ml of blood mentation.

inoculated into four bottles with the following nutrient The clinical picture in the present case resembled http://jcp.bmj.com/ media: trypticase soy broth, trypticase soy broth with chronic meningococcaemia (Benoit, 1963). Chills, 0 7 % mucin, brain-heart infusion with para-aminobenzoic skin acid, and thioglycollate (Hochstein, Kirkham, and fever, rash, arthralgias and arthritis, headache, Young, 1965). The colonies showed golden yellow and a history of dental work were present. Fever pigment formation on Leoffler's serum media. The was intermittent and the patient was essentially organism was oxidase positive and failed to produce acid well between the episodes of fever. The skin rash from sugars. Agglutination occurred with a polyvalent was polymorphous with maculo-papular, nodular neisseria antiserum and types A, B, C, D antisera; and pustular lesions, and the patient reported that however, the quelling reaction was negative indicating her rash resembled insect bites as is often the case on September 24, 2021 by guest. Protected copyright. a nonspecific reaction consistent with cross-reactivity of in chronic meningococcaemia. The rash appeared a chromogenic neisseria. The organism isolated from in the characteristic 'shower' on the extensor surface each of the four positive blood cultures gave a 1:160 titre of the the trunk and mucous membranes with N. flavescens antiserum, a positive titre with this extremities, antiserum being 1:20 or greater. These characteristics being relatively spared. The skin lesions were also identified the organism isolated from the blood cultures indistinguishable from those of gonococcaemia as Neisseria flavescens. (Abu-Nassar, Hill, Fred, and Yow, 1963). After a provisional diagnosis of meningococcaemia The severity of arthralgias and myalgias paralleled treatment was initiated using procaine penicillin, 1,200,000 the fever curve and arthritis did not develop until units intramuscularly every six hours, and sulphisoxazole the third bout of fever at the time of development 4-0 g initially and then 2-0 g orally every six hours. There of the skin rash. The clinical features of local pain, was rapid recovery withthis therapy. Penicillinwas stopped tenderness, swelling, redness, and heat are those after five days, and sulphisoxazole continued for a total of any infectious arthritis, but the transient nature of two weeks. The patient has remained well during 18 months of observation after treatment. with involvement of smaller joints has been reported (Pinals and Ropes, 1964) to be a frequent occur- rence in meningococcal arthritis. DISCUSSION The headache was generalized, throbbing in nature and most severe during the height of the N. flavescens was first described (Branham, 1930) fever. Although this organism, like the meningo- J Clin Pathol: first published as 10.1136/jcp.21.4.437 on 1 July 1968. Downloaded from

Septicaemia caused by Neisseria flavescens 439 coccus, tends to localize in the meninges, there was REFERENCES no evidence of infection of this site in this patient. Abu-Nassar, H., Hill, N., Fred, H. L., and Yow, E. M. (1963). The therapy was that of any neisserial infection Arch. intern. Med., 112, 731. with a sulphonamide as the primary agent, and Benoit, F. L. (1963). Amer. J. Med., 35, 103. Branham, S. E. (1930). Pub!. Hlth Rep. (Wash.), 45, 845. penicillin was added to cover the possibility of Hochstein, H. D., Kirkham, W. R., and Young, V. M. (1965). New sulphonamide resistance or a gonococcal aetiology. Engl. J. Med., 273, 468. Pinals, R. S., and Ropes, M. W. (1964). Arthr. and Rheum., 7, 241. The response was as prompt as that usually seen Noguchi, T. T., Nachum, R., and Lawrence, C. A. (1963). Med. with successful treatment of the meningococcal and Arts Sci., 17, 11. Prentice, A. W. (1957). Lancet, 1, 613. gonococcal infections, including chronic meningo- Ruiz Sanchez, F., Ruiz Sanchez, A., Negrete, D., and Rodriguez, L. coccaemia. (1963). Medicina (Mix.), 43, 25. http://jcp.bmj.com/ on September 24, 2021 by guest. Protected copyright.