TOXIC SHOCK SYNDROME AFTER A MINOR SURGICAL PROCEDURE

1330 of the rectal mucosa with a lignocaine gel for patients with ulcerative proctitis and colitis resulted in good symptomatic relief and restored mucosal integrity, indicatingaa pathogenetic role for hyperactive enteric nerves. Hyperplasia of the mucosal innervation with adrenergic, cholinergic, and peptidergic nerves was demonstrated but was not influenced by the treatment. Lymphocyte infiltration was clearly reduced.

Topical

Letters to the Editor LIGNOCAINE AND ULCERATIVE PROCTITIS

SIR,-The initial abnormality of ulcerative colitis is congestion and dilatation of the capillary blood supply, which leads to mucosal haemorrhage and necrosis of epithelial cells. Goblet cells are reduced in their mucus content.’ An imbalance in the autonomic nervous system may cause a changed vasomotor tone, serving as a possible pathogenic factor. Hyperplasia of the mucosal adrenergic innervation in ulcerative colitis has been demonstrated histochemically by formaldehyde-induced fluorescence of biogenic amines.2 Secondary to the mucosal damage, lymphocytes and plasma cells accumulate in the lamina propria, together with foci of polymorphonuclear cells from which crypt abscesses may form. Subsets of lymphocyte populations in the inflamed mucosa have been studied immunocytochemically, showing a predominance of suppressor-cytotoxic phenotype (OKT 8-) within the epithelium and of helper type (OKT 4) within the lamina propria.3 Experimental studies on acute inflammatory states in the small intestine have established the involvement of enteric nerves in secretory reflexes. Secretion was reduced or abolished by drugs interfering with such reflexes (eg, topical lignocaine). Thus, our hypothesis was that blockade of enteric nerves by lignocaine might reduce the inflammatory response in patients with ulcerative

proctitis. In patients with ulcerative proctitis or limited, left-sided colitis lymphocyte infiltration, goblet cells, and innervation of the mucosa were studied in biopsy samples taken before, during, and after topical treatment of the rectal mucosa with a lignocaine gel for up to 2 months. The clinical response (symptoms and proctoscopic) findings was evaluated every 2-3 weeks. Ten patients, selected at random, with histopathologically diagnosed ulcerative proctitis (seven) or colitis (three) were studied. The duration of disease was less than one year. All patients had 3-6 bowel movements daily with discharge of blood and mucus. Proctoscopy confirmed moderate-to-severe inflammation. Three patients had been treated with a combination of prednisolone enemas and salazopyrine. No treatment was given for one month before the study. The patients applied a 2% lignocaine gel (Astra) intrarectally three times daily (10, 10, and 20 ml, total dose 800 mg). The first five patients were treated for 3 weeks, the other five for 4-8 weeks. No side-effects were noted. Rectal irritability and bowel movements were decreased within the first few days. After 3 weeks all patients had a normal frequency, no discharge of blood and mucus, and a macroscopically intact mucosa. Rectal biopsy samples (at 10 and 25 cm) from four patients, treated for 6-8 weeks, were studied immunocytochemically with antisera directed against OKT4- or OKT8-. Before treatment these lymphocyte subsets massively invaded the lamina propria and epithelium. Accumulation of OKT8 lymphocytes were also seen in crypts, forming abscesses. At the end of treatment very few lymphocytes of these subsets were found, suggesting a diminished immune response. Staining with alcian-blue for goblet cells revealed that within 3 weeks of treatment the mucus content was restored to levels comparable with those found in age-matched healthy controls. Rectal biopsy samples from all ten patients before treatment were studied immunocytochemically with antisera directed against tyrosine hydroxylase, neuropeptide Y, substance P, and the Schwann cell protein (S-100) and were post-stained for acetylcholinesterase (AChE). Compared with control data the number of nerve terminals with tyrosine hydroxylase-like immunoreactivity was much increased, and individual nerve terminals appeared more prominent. Substance P apart, all patients with ulcerative proctitis displayed a pattern of hyperplastic innervation in the diseased segment but had normal innervation in the upper biopsy specimen. Patients with ulcerative colitis had these findings at both biopsy sites. This abnormal mucosal innervation pattern persisted in all patients after treatment.

treatment

3-8 weeks in

Department of Surgery, Lundby Hospital, S-417 17 Goteborg, Sweden

S. BJORCK

Institute of Neurobiology, University of Goteborg

H. AHLMAN A. DAHLSTROM

Pathology of ulcerative colitis. In: Kirsner JB, Shorter RG, eds Inflammatory bowel diseases Philadelphia: Lee & Febiger, 1975: 167-91. Kyosola K, Penttila O, Salaspuro M Rectal mucosal adrenergic innervation and

1. Morson BC. 2.

J Gastroenterol 1977; 12: 363-67. 3 Selby WS, Janossy G, Bofill M, Jewell DP Intestinal lymphocyte subpopulations in inflammatory bowel disease: an analysis by immunohistological and cell isolation techniques Gut 1984; 25: 32-40. enterochromaffin cells in ulcerative colitis and irritable colon. Scand

4. Brunsson I. Acute inflammatory diarrhea in the small intestine. an experimental study of secretory mechanisms in rats and cats. Academic dissertation, department of physiology, University of Goteborg, 1987 (ISBN 91-7900-312-5).

TOXIC SHOCK SYNDROME AFTER A MINOR SURGICAL PROCEDURE

SiR,—The toxic-shock syndrome (TSS), first reported as a childhood disease,’ has become better known as a tamponassociated disease in menstruatmg women. It has also become recognised as a complication of elective surgeryZ.3 and bums in children.’ The syndrome is caused by a strain of Staphylococcau aureus producing TSS toxin-l (TSST-1). This toxin is responsible for the multisystem abnormalities (diarrhoea, vomiting,

tachycardia, hypotension, fever, central-nervous-system disorders, liver and renal failure, and so on) and for the typical rash and the late desquamation. In burned children there is a prodromal phase over the first few days after injury, with irritability and fever (often over 40°C); and this is followed by gastrointestinal disturbances. The shock phase then develops, usually 3-5 days after the bum, and it can be fatal unless treated appropriately. The rash appears on about the 3rd day and the skin in survivors typically desquamates in the clefts between the fingers and toes in the second week. At this unit children admitted with bums

are

monitored very

carefully and if TSS is suspected clinically we administer immunoglobulin, as fresh whole blood or fresh frozen plasma. Blood from donors older than 30 years of age has a 95% chance of containing antibodies to TSST-1,’’ and transfusion of blood products containing immunoglobulins should combat the syndrome in the young burns victim, who may have no antibody. In our experience neither prophylaxis nor treatment with antibiotics is appropriate in burned children. Because of the general lack of awareness of TSS and its treatment in the surgical patient we report here the case of a 17-year-old boy who had a routine bat-ear correction as a day case on March 24, 1988. Over the first 3 postoperative days he became generally unwell with irritability, vomiting, diarrhoea, headaches, photophobia, generalised myalgia, neck pains, and fever (39°C). A macular rash developed from the second day and both his hands swelled up. The provisional diagnosis was meningitis and he was transferred to an infectious diseases unit. He was drowsy, dehydrated, tachycardic and had a blood pressure of 100/20 mm Hg. He had severe conjunctivitis and pharyngitis with oral ulceration and tender cervical lymphadenopathy. He had neck stiffness but a negative Kernig’s sign and the ear wounds did not look grossly infected. A lumbar puncture did not confirm meningitis but his blood urea was 25 mmol/1 (normal 6-7), creatinine 278 J.1tl1ol/l (44-120), albumin 24 g/I (35-50), and corrected serum calcium 2-29 mmol/1 (230-270); his platelet count fell to 88 x 109/1 (150-500); heterophile antibodies were negative. Faced with a sick patient but no clear diagnosis the clinicians prescribed rehydration with intravenous crystalloid and benzylpenicillin, gentamicin, flucloxacillin, and hydrocortisone. The next day he was still unwell and the benzylpenicillin was

1331

replaced by ceftazidime. The patient recovered slowly over the next 10 days but desquamation in the web spaces of his hands and feet

noted 10 days after the rash had started. Culture of the and his throat grew Staph aureus, one of a pair of blood culture from was isolated aureus and Staph bottles after a 4 day extended incubation period. Three other paired blood cultures showed no growth. The staphylococci isolated from the wounds and blood culture were later identified as TSST-1 producing. Despite appropriate antibiotics the staphylococcus was still present on swabs taken from the ear wound 6 days after was

post-auricular surgical wounds

admission. This case should serve as a reminder for all surgeons to be aware of the possibility of TSS even after a very minor procedure. This patient might have recovered more quickly if TSS had been diagnosed earlier and if a blood product containing gammaglobulin had been administered. High-dose antistaphylococcal antibiotics or tropical antistaphylococcal agents such as mupirocin have a limited value in established TSS because it is a toxin-mediated disease. North-East Thames Regional Bums and Plastic Surgery Unit, St Andrew’s Hospital, Billericay, Essex 1 Todd J, Fishaut M,

2

Kapral F, Welch

JAMES D. FRAME MICHAEL HACKETT T Toxic-shock

syndrome associated with

phage-group-1 staphylococci. Lancet 1978; ii: 1116-18. Tobin G, Shaw RC, Goodpasture HC. Toxic shock syndrome following breast and

nasal surgery. Plast Reconstr Surg 1987; 80: 1111-14 3. LoVerme WE, Drapkin MS, Courtiss EH, Wilson RM Toxic shock syndrome after chemical face peel. Plast Reconstr Surg 1987; 80: 1115-18. 4. Frame JD, Eve MD, Hackett MEJ, et al. The toxic shock syndome in burned children Burns 1985; 11: 234-41. 5 Davis JP, Vergeront JM, Chesney PJ. Possible host-defense mechanisms in toxic shock syndrome. Ann Intern Med 1982; 96: 986-91.

HIGH INCIDENCE OF ANAPHYLACTIC REACTIONS TO CEFACLOR

SIR,-Cefaclor is prescribed worldwide’ and is one of the most frequently prescribed oral antibiotics in Japan. Many serum sickness type reactions to cefaclor have been reported.2.3 Patients administered cefaclor had a higher frequency of serum sickness type reactions and urticaria than those prescribed amoxycillin.1 Although several anaphylactic reactions to cefaclor were reported in Japan,s such reactions have not been reported elsewhere. We have seen four cases of anaphylactic reactions to cefaclor prescribed in our

hospital.

In the first case, a 27-year-old woman was given one 250 mg capsule of cefaclor with other drugs for treatment of an upper respiratory tract infection. Within 30 min urticaria appeared. When she revisited the hospital 1 h after taking the drugs, she fainted; systolic blood pressure was 70 mm Hg. Hydrocortisone, chlorpheniramine, adrenaline, and lactate Ringer’s solution were administered immediately. Systolic blood pressure fell to 30 mm Hg but gradually increased to 94 mm Hg during the infusion of dopamine at 20 ug/kg/min for about 15 min. She was admitted and the dopamine infusion was tapered off over 6 h. She was discharged 2 days later. Intradermal skin-testing was done 10 months later. She reacted positively to 06 ug cefaclor. Cases 2 (a 51-year-old man) and 3 (a 33-year-old woman) had typical anaphylactic reactions. Both reacted positively to intradermal tests, the first to 0ng and the other to 0-6 ltg cefaclor. In the fourth case (a 73-year-old man) systolic blood pressure fell to 60 mm Hg about 40 min after he took a capsule of cefaclor and a tablet of bromhexine. Although skintesting could not be done cefaclor was probably responsible because anaphylactic reactions to bromhexine have not been reported. We have also seen 3 cases of haematological disorders (pancytopenia with liver damage, agranulocytosis, and agranulocytosis plus thrombocytopenia with shock) induced by cefaclor which was prescribed outside our hospital. All of these cases were confirmed to be cefaclor-induced by a lymphocyte stimulating test. Another case of severe anaphylactic reaction to cefaclor prescribed outside our hospital has been brought to our attention. A 57-year-old man had urticaria, dyspnoea, cyanosis, and stupor after taking one capsule of cefaclor, although he had, a fortnight before this, taken cefaclor safely for 5 days. He reacted positively to 06 gg intradermal cefaclor.

The number of patients to whom cefaclor has been prescribed at least once at our hospital between the introduction of cefaclor

(March, 1982) and March, 1987, was 7972. Cephalexin, ampicillin, amoxycillin were prescribed to 24 421, 20 987, and 13 152 patients, respectively, between April, 1979, and March, 1987. The total number of patients to whom injectable penicillins and cephems were prescribed at least once in this period was 10 936. The number of anaphylactic reactions reported in our hospital between April, 1979, and March, 1987, was: 4 to cefaclor, 1 to cephalexin, and 1 to ampicillin.6 The incidence per 10 000 patients of anaphylactic reactions was 5 02 for cefaclor, 041 for cephalexin, 0-48 for ampicillin, and zero for amoxycillin and for injectable penicillins or cephems. The incidence of anaphylactic reactions to cefaclor was more than ten times higher than that to other antibiotics, including injectables (p < 0-05, Fisher’s exact test). In Japan, pharmaceutical companies are required to do postmarketing surveys for new drugs. There were no reports of anaphylactic reactions among 70 146 cephalexin takers and 57 970 amoxycillin takers, while 5 cases were reported among 35 146 patients on cefaclor. The incidence rate was significantly higher in patients on cefaclor than on cephalexin or amoxycillin (p < 001 ). The rate is lower than that of injectable cephems (.0-024%) but higher than that of injectable cephems (0 - 0-013%). A fatal case of shock, probably induced by cefaclor, has been reported.5 Such a high incidence of anaphylactic reactions to cefaclor (about 1 /200) might require intradermal skin pretesting, as with injectable penicillins and cephems. Cefaclor, however, is an oral antibiotic. We believe that cefaclor should not be recommended as a first-line drug. Department of Internal Medicine and Pharmacy, Hannan Chuo Hospital, Matsubara City, Osaka 580, Japan

ROKURO HAMA KUMIKO MORI

1 Col NF, O’Connor RW Estimating worldwide current antibiotic usage Report of task force 1. Rev Infect Dis 1987; 9 (suppl): S232-43 2 Murray DL, Singer DA, Singer AB. Cefaclor. a cluster of adverse reactions. N Engl J Med 1980; 303: 1003. 3. Swedish Adverse Drug Reactions Advisory Committee. Hypersensitivity reactions to cefaclor. Bull SADRAC 1986; no 47: 2-3. 4. Levine LR. Quantitative comparison of adverse reactions to cefaclor vs amoxycillin in a surveillance study. Pediatr Infect Dis 1985; 4: 358-61. 5. Ministry of Health and Welfare. Cefaclor-induced shock. Information Adverse Drug React 1987; No 84: 1-2 (in Japanese). 6. Hama R, Hashimoto N, Okamoto Y, Mon K, Kuroda M, Mochizuki I: Adverse drug reaction monitoring system using the ambulatory disease registration system. In: Lindberg DAB, Kaihara S, eds. Proc Third World Conf Med Infomatics (MEDINFO 80). Amsterdam. North-Holland Publishing Company, 1980: 905-09.

NEW LIFE FOR THE EEG

SiR,—Clinical neurophysiologists will find much to agree with in your April 30 editorial. The new methods of quantitative EEG and brain mapping have potential, both clinically and in research, but they need to be properly evaluated quickly, before enthusiasm outruns discretion and money is spent in the wrong places. Where we would take issue is with your assessment of the current situation. To suggest that "Interest in the EEG has declined to a point where it is usually requested only in misguided attempts to ’exclude’ seizures" is to deny the value of this investigation in many unexplained psychiatric illnesses. These include reversible metabolic disorders such as hyponatraemia, temporal lobe status, and atypical encephalitides presenting as acute psychosis or confusion-indeed, the EEG is underused in acute confusional states, perhaps the commonest neuropsychiatric disorder presenting in a general hospital. They also include epilepsy, or the more rare cerebral degenerative conditions, presenting as behaviour disorders in children. The need to exclude significant cerebrovascular disease or Alzheimer type dementia in patients who present with depression and anxiety in middle or old age is becoming more important, and the EEG is a useful tool in this

respect.’1 It is wrong to state that interest in the EEG is now restricted seizure disorders. In most hospitals EEG referrals are as likely

to to