1288

encapsulated, solid, or cystic lesions with an incidence of 1 in 35 000 a female preponderance of 4/1.1 Exceptionally these tumours are observed in adults (incidence 1 in 87 000 and female/male ratio 10/1).2 In the newborn baby 35% are malignant; however malignant disease is rare after the second decade.3 The differential diagnosis of masses in this region includes chordoma, meningocoele, neurofibroma, fibrosarcoma, giant cell tumour of the sacrum, pilonidal cyst, osteomyelitis of the sacrum, and tuberculosis; all these are uncommon. Adults usually present with features of perirectal inflammatory disease that suggest perirectal abscess or fistula, with pain and discharge. Rarely, obstructed defaecation occurs. Neonatal presentation of postsacral tumours is usually with a visible gluteal or midline mass. Malignant presacral tumours usually occur in the infant with a characteristic triad of constipation, urinary frequency, and leg weakness.3 and

Cases of sacrococcygeal teratoma are very rare, especially in adult men.’ Our case seems unique in that onset of symptoms was very rapid and presentation was similar to that of malignant presacral teratoma in the infant. The mass in our case was considered benign, but the condition is so rare that an accurate prognosis could not be indicated. The treatment of choice for benign and malignant tumours is surgical excision.5 The major complications of surgery are excessive haemorrhage, neurogenic bladder problems due to sacral plexus damage, and recurrence. The coccyx should be removed routinely, not only for exposure, but to remove the nidus which may contain totipotent remnants. Recurrence is common if the coccyx is incompletely excised.2

J. M. WILKINSON

University Department of Surgery, Royal Hallamshire Hospital,

K. B. HOSIE C. J. STODDARD

Sheffield S10 2JF, UK

1. Altman RP, Randolph JG, Lilly JR. Sacrococcygeal teratoma: American Academy of Pediatrics Surgical Section Survey, 1973. J Pediatr Surg 1974; 9: 389-98. 2. Miles RM, Stewart GS. Sacrococcygeal teratomas in adults. Ann Surgery 1974; 179: 676-83. 3. Pantoja E, Rodriguez-Ibanez I. Sacrococcygeal dermoids and teratomas: historical review. Am J Surg 1976; 132: 377-83. 4. Ahmed HA, Pollock DJ. Malignant sacrococcygeal teratoma in the adult. Histopathology 1985; 9: 359-63. 5. Gross RE, Clatworthy HW, Meeker IA. Sacrococcygeal teratomas in infants and children: a report of 40 cases. Surg Gynecol Obstet 1951; 92: 341-54.

Micrometastatic tumour cells in bone marrow in colorectal cancer

investigated patients with proven metastatic disease of colorectal carcinoma (T 1-4, N 0-1, M 1; n = 12) and those with radically resected colorectal cancer without evidence of metastases (T 1-4, N

0-4, M 0; n=7). In the 12 patients with metastatic disease only 2 had tumour cells in bone marrow (1with 1 cell and 1 with 5 cells per 106 mononuclear bone marrow cells). Obviously findings in bone marrow do not indicate the total tumour load in this phase of disease, possibly tumour

cells have all adhered

to

the organs that

are

the

preferential sites for metastatic disease of colorectal cancer. In the 7 patients with radical resection, we performed bonemarrow aspiration 2-6 weeks after tumour resection, and not preoperatively as Lindemann’s group did. Before resection the number of tumour cells found in the bone marrow might reflect the disseminating activity of the primary tumour. On the other hand the of tumour cells still present in the bone marrow after so-called radical resection cannot be explained by continuing spread of the primary tumour. We found tumour cells in the bone marrow in 5 of 7 patients (1,3,4,48, and 60 per 106 cells, respectively). The observation time in these 7 patients was 11-32 months (median 27). It is noteworthy that disease in the 2 patients with a very high number of tumour cells had an unfavourable course. 1 died of overt metastases 11 months after tumour resection, and the other had a amount

disease had been noted so far, which gives the impression that a high number of tumour cells residing in the bone marrow after radical resection of the primary tumour is very dangerous. If our observations were confirmed by more comprehensive studies, they might raise the possibility that adjuvant therapy is

required.

Department of Medicine, Karl Franzens University, A-8036 Graz, Austria

HEINZ SILLY HELLMUT SAMONIGG HERBERT STOGER HANS PETER BREZINSCHEK MARTIE WILDERS-TRUSCHNIG

Death from tetanus in sickle-cell disease SIR,-Dr Akpede’s instructive report (Oct 17, p 981) about the

rapid death from tetanus of a child with sickle-cell anaemia confirm danger such patients are in when lung ventilation is compromised. This can happen iatrogenically during general anaesthesia in incompetent hands,’ with the use of large doses of morphine to treat sickle crisis, or in conditions such as bronchial asthma which worsen the prognosis of sickle-cell disease,’ and with tetanus. Akpede says that haemoglobinopathies are not usually what grave

associated with a poorer outcome in tetanus, but I have described death from tetanus in an 18-year-old woman with sickle-cell anaemia.’ Ventilatory problems appearing in sickle-cell disease should always be regarded as a medical emergency so that continuous oxygen is started early. Opioids should be avoided in crisis2°3 and instead of continuous morphine’5 (which often produces "the chest syndrome"), diclofenac suppositories alone or with ketorolac6 should be used. General anaesthesia in competent hands is remarkably safeIn the tropics one should also ensure that tetanus vaccines have not expired, and that they have not been sitting at some airport for months before clearance. Cromwell Hospital, London SW5 0TU, UK 1. 2 3.

F. I. D. KONOTEY-AHULU

Konotey-Ahulu FID. The sickle cell disease patient. London: Macmillan, 1991. Serjeant GR. Sickle cell disease. Oxford: Oxford University Press, 1985: 204 Konotey-Ahulu FID Morphine for painful crisis in sickle cell disease. BMJ 1991,

302: 604. 4. Brozović M. Sickle cell disease. Prescribers’ J 1992; 32: 45-55. 5. Harrison JFM, Liesner R, Davies SC. Pethidine in sickle cell crisis. BMJ 1992; 305: 182. 6. Goodman E. Use of ketorolac in sickle cell disease and vaso-occlusive crisis. Lancet

1991; 338: 641-42.

SIR,-Dr Lindemann and colleagues (Sept 19, p 685) report that preoperatively detected tumour (cytokeratin positive) cells in the bone marrow of patients with colorectal carcinoma represent an independent and strong determinant of relapse after radical resection. We learned this technique from these workers and have

because

local relapse after 21 months. In the other 5 patients no evidence of

7. Oduro KA, Searle JF. Anaesthesia in sickle states: a plea for simplicity. BMJ 596-98.

1972; iv:

Liver dysfunction, anaemia, and granulocytopenia after exanthema subitum SIR,-Since Yamanishi et all found that human herpesvirus-6 (HHV-6) caused exanthema subitum, severe cases of HHV-6 infection have been reported. 2,3 We report a case of progressive liver dysfunction, anaemia, and granulocytopenia associated with HHV-6 infection. The patient was a 6-month-old girl. On Jan 19, 1992, she had fever due to otitis media. 7 days later, she again had fever and exanthema, and was referred to our hospital because of poor suckling and irritability. She was mildly dehydrated and had hepatosplenomegaly. Serum alanine aminotransferase (ALT) and aspartate’ aminotransferase (AST) were 572 and 274 lUll, respectively. On admission, laboratory analysis revealed anaemia

(haemoglobin [Hb] 10.7 g/dl), granulocytopenia (segementation 1 %, band 1 %), and positive C-reactive protein (2-6 mg/ml). We diagnosed exanthema subitum and suspected that the liver dysfunction, anaemia, and granulocytopenia were caused by a virus that induced exanthema subitum. She was not given therapy except for transfusion. However, exanthema, high temperature, and liver dysfunction recurred and C-reactive protein values were the same. On March 31, she had a liver biopsy. Intralobular spotty necrosis of liver cells was observed on light microscopy, without significant pathological changes in portal triads. We examined the HHV-6

1289

Serum aminotransferases and HHV-6 antibody titre.

antibody titres of her

serum, because serum antibody titres for viruses that induce liver dysfunction generally were negative. HHV-6 antibody rose from under 10 at admission to over 1280 after 4 days, and high titres were maintained for 3 months (> 1280) (figure). We suspected that her symptoms were caused by chronic HHV-6 infection and began daily intravenous injection of stronger neominophagen C (SNMC) containing glycyrrhizon and subcutaneous injections of recombinant G-CSF 25 ug (GRAN, Sankyo). SNMC therapy was ineffective. Her liver dysfunction worsened and granulocytopenia (segmentation 0%, band 0%) and anaemia (Hb 7-8 g/dl) continued. In May, she had mild jaundice (total bilirubin 1 4 mg/dl) and in June her aminotransferase values were increased (ALT 1949 and AST 1155 IU/1). To reduce virus activity, we administered interferon-ot (IFN-(x, Sumitomo) by daily subcutaneous injection, similar to the protocol for chronic hepatitis caused by hepatitis B or C viruses. We started at 20 000 U/kg per day and increased to 80 000 U/kg per day. Liver dysfunction improved (ALT 517 and AST 393 IU/1) 1 month later, and granulocytopenia and anaemia

slight degenerations were revealed by staining with haematoxylin and eosin. Thus first infection with or reactivation of HHV-6 during pregnancy may predispose to spontaneous abortion. Department of Obstetrics and Gynaecology, Nara Medical University, Kishihara, Nara, 634, Japan

YOSHIYA ANDO KAZUHIRO KAKIMOTO YUTAKA EKUNI MOTOHIKO ICHIJO

1. Yamanishi K, Okuno T, Shiraki K, et al. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet 1988; ii: 1065-67. 2. Pietroboni GR, Harnett GB, Bucens MR, et al. Antibody to human herpesvirus 6 in saliva. Lancet 1988; i: 1059. 3. Asano Y, Yoshikawa T, Suga S, et al. Human herpesvirus-6 harbouring m kidney. Lancet 1989; ii: 1391. 4. Okukno T, Takahashi K, Balachandra K, et al. Seroepidemiology of human herpesvirus 6 infection in normal children and adults. J Clin Microbiol 1989; 27: 651-53. 5. Levy JA, Ferro F, Greenspan D, et al. Frequent isolation of HHV-6 from saliva and high seroprevalence of the virus in the population. Lancet 1990; 335: 1047-50. 6. Okuno T, Higashi K, Shiraki K, et al. Human herpesvirus 6 infection in renal transplantation. Transplantation 1990; 49: 519-22.

improved slowly. There have been

no

reports of

progressive liver dysfunction,

anaemia, and granulocytopenia associated with HHV-6 infection. All the symptoms in our case were suspected to have been caused by HHV-6 chronic active infection because of the clinical symptoms and the changes in HHV-6 antibody titre. We thank Dr K. Yamanishi for help with

measurement

of HHV-6

antibody titres. TAKAKO TAKIKAWA HIROSHI HAYASHIBARA YUICHIRO HARADA KAZUO SHIRAKI

Department of Pediatrics, Faculty of Medicine, Tottori University, Yonago 683, Japan

1 Yamanishi K, Okuno T, Shiraki K, et al. Identification of human herpesvirus-6 as a causal agent for exanthema subitum. Lancet 1988; i: 1065-67. 2. Tajiri H, Nose O, Baba K, Okada S. Fatal fulminant hepatitis in an infant with human herpesvirus-6 infection. Lancet 1990; 335: 863. 3. Prezioso PJ, Cangiarella J, Lee M, et al. Fatal disseminated infection with human

herpesvirus-6. J Pediatr 1992; 120: 921-23.

HHV-6 infection

during

pregnancy and

spontaneous abortion SIR,-Human herpesvirus-6 (HHV-6) is the causative agent of exanthema subitum.1 We have examined the effect of HHV-6

infection in early pregnancy. Serum HHV-6 IgG and IgM antibodies2-5

were assayed in 30 patients with spontaneous abortion in weeks 6-12 of pregnancy. Villous tissue was collected in these patients to look for HHV-6 antigen with OHV-1," an HHV-6 monoclonal antibody (obtained, with thanks, from Professor Yamanishi at the Institute for

Microbiological Research, Osaka University). Mean serum HHV-6 IgG and IgM antibody titre in the patients was 160, which contrasts with a mean titre in normal pregnant women of 40.3 patients (10%) were positive for HHV-6 IgM antibody. HHV-6 antigen was detected in abortive villous tissue of 2 of the 3 IgM-positive patients. Changes such as swollen symplasts and

Acute adrenal insufficiency after discontinuation of inhaled corticosteroid

therapy SIR,-In asthmatic adults, inhaled steroids are recommended as safe and without serious side-effects.!,2 In children, growth velocity may be reduced by doses of inhaled steroids higher than 400 ug daily.3 A few cases of growth retardation and hypercortisolism in patients on long-term low-dose inhaled corticosteroid have been described.’ Suppression of the hypothalamic-pituitary-adrenal axis has been documented, but usually without clinical consequences.4-