Subcutaneous gammaglobulin for patients with secondary hypogammaglobulinaemia

decreased greatly once military action began. This reduction was attributed to the change in food supplies; fresh local produce was widely used during the early phase, but prepacked western supplies were used once the military action escalated.2 In our view, the use of single-dose ciprofloxacin for travellers’ diarrhoea is encouraging. However, careful evaluation is needed of the impact of this disease on operational effectiveness before widespread use can be recommended in a military setting.

could deprive the local population of one of a few remaining effective drugs. Perhaps it would have been better for the wider good had the soldiers foregone ciprofloxacin and run the risk of socalled Belize belly. *Dermot Maher, A D Harries College of Medicine, University of Malawi, Private Bag 360, Chichiri, Blantyre 3, Malawi

Murray BE, Alvarado T, Kim K-H. Increasing resistance to trimethoprim-sulfamethoxazole among isolates of Escherichia coli in developing countries. J Infect Dis 1985; 152: 1107-13.

1

*M P Connor, A D Green RAF Institute of Pathology and Tropical Medicine, Halton, Buckinghamshire HP22 5BW, UK

Aylesbury,

Elliot J, Connor MP, Green AD. Gastrointestinal disease amongst RAF personnel in Belize. Trans R Soc Trop Med Hyg 1994; 88: 373. Kilpatrick ME. Diarrhoeal disease: a military perspective. Trans R Soc Trop Med Hyg 1993; 87 (suppl 3): 47-48.

1 2

SIR-We are concerned about the consequences of Salam and colleagues’ conclusions. First, the study is confined to a very specific populationnamely, professional soldiers. These men will be very fit, perhaps used to travelling to different parts of the world, and are thus a very different population from the average traveller abroad. Second, the numbers are small and the results could have arisen by chance. More importantly, the small numbers considerably reduce the chances of seeing any complications of therapy. Pseudomembranous colitis, thrombocytopenia, and Stevens-Johnson syndrome, though rare, are well-recognised and dangerous complications of ciprofloxacin therapy.’ It is not sufficient to conclude that the small dose used will be cost-effective, free of side-effects, and unlikely to produce resistance, when one considers the potential numbers of patients who will probably use such a treatment if it is widely introduced. UK residents undertake more than 30 million overseas journeys each year, and 30-50% might develop diarrhoea.2 Such vast numbers of people seeing their general practitioner for tablets before going on holiday would swamp an already overburdened service. Third, the follow-up period does not allow for the detection of possible rebound diarrhoea. We feel that Salam’s study has drawn attention to an important issue, but larger randomised controlled trials are needed in a more representative population, and guidelines should be developed for the most appropriate usage.

Topical treatment for Dupuytren’s contracture SIR-Since Shelley and Shelley’s report’ of success with topical 0-05% clobetasol propionate cream (Dermovate) twice daily and 0-05% tretinoin cream (Retin-A) once daily in Dupuytren’s contracture, I have faithfully used this treatment. These workers did not indicate how many patients were thus treated but state that in one who had had a painful fibrous cord extending up the fourth finger for 9 months, after 3 months the pain resolved and by 9 months the contracture was no longer present and the skin was normal. At my age, wishing to avoid surgery under general anaesthesia for what must be regarded as a minor disability, I have now continued with this topical therapy for 17 months. Sad to say during this period my condition has regressed. I have increasing difficulty in typing and cutting my finger-nails and toe-nails and can no longer wear a glove on my right hand. Long-term assessment of any therapeutic regimen must be subjected to constant review. Because I personally have failed to respond to this therapy as advocated is not a criticism of such advice given. Nevertheless, can Shelley and Shelley verify that they are still having success as presented and what percentage of patients completely respond as described in their letter? I wonder if any of your readers who are fellow-sufferers have benefited from topical therapy and if any further clinical trials support its efficacy?

Anthony G

1

*Christine Hall, John Cornell

Freeman

Meadow Rise, 3 Lakeside, Swindon, Wiltshire SN3

1QE, UK

Shelley WB, Shelley ED. Response of Dupuytren’s potency topical steroid. Lancet 1993; 342: 366.

contracture to

high

Rotherham Health Authorities, Rotherham, South Yorkshire S65 2QU, UK

1

2

British National Formulary. London: British Medical Association Pharmaceutical Press, September, 1994. Health advice for travellers 1994. Department of Health. London: HM Stationery Office 5/94.

SIR-Although Salam and colleagues suggest that "shortterm therapy may also be less likely to promote emergence of drug resistance", they ignore the wider issues of drug resistance. Indiscriminate use of antibiotics for benign, self-limiting infections fuels the rapid evolution of resistance, which limits the duration of their effectiveness. In developing countries the availability of antibiotics to which enteric pathogens remain susceptible is an increasing problem.’ Individuals with severe enteric infections such as cholera, dysentery, or invasive salmonellosis may die because an effective antibiotic is not available. Visitors’ use of new antibiotics such as ciprofloxacin promotes resistance in enteric pathogens and 382

gammaglobulin for patients with secondary hypogammaglobulinaemia

Subcutaneous

SIR-Patients with secondary humoral immunodeficiencies as such hypogammaglobulinaemia resulting from haematological malignancies frequently get bacterial infections which are associated with substantial mortality. Prophylaxis with intravenous gammaglobulin was shown to be effective in preventing bacterial infections in a blinded multicentre study,’ and it is currently recommended that patients with low-grade B-cell tumours, such as chronic lymphocytic leukaemia (CLL) or lymphomawho have had a severe infection and display low concentrations of total IgG or of antibodies against pneumococcal capsular polysaccharides3 should be treated with intravenously administered gammaglobulin. However, because of the costs involved, this recommendation has not been widely accepted. Rapid subcutaneous infusion of gammaglobulin

Subcutaneous gammaglobulin prophylaxis may thus be a valuable alternative form of treatment and, since the route of administration would not be expected to influence the prophylactic properties of the gammaglobulin, may in fact represent the treatment of choice in different forms of secondary immunodeficiencies. *Lennart

Hammarström, Jan Samuelsson, Gunnar Grimfors

*Department of Clinical Immunology, Huddmge Hospital, S-14186 Huddmge, Sweden; Department of Internal Medicine, South Hospital, Stockholm; and Department of Internal Medicine, Karolinska Hospital, Stockholm

1

2

3 *Based on the time between occurrence of first institution of gammaglobulin prophylaxis.

major

infection until time of

4

Cooperative group for the study of immunoglobulin in chronic lymphocytic leukemia. Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. N Engl J Med 1988; 319: 902-07. Griffiths H, Brennan V, Lea J, Bunch C, Lee M, Chapel H. Crossover study of immunoglobulin replacement therapy in patients with low grade tumors. Blood 1989; 73: 366-68. Griffiths H, Lea J, Bunch C, Lee M, Chapel H. Predictors of infection in chronic lymphocytic leukaemia. Clin Exp Immunol 1992; 89: 374-77. Gardulf A, Hammarström L, Smith CIE. Home treatment of hypogammaglobulinaemia with subcutaneous gammaglobulin by rapid infusion. Lancet 1991; 338: 162-66. Thomas MJ, Brennan VM, Chapel HH. Rapid subcutaneous immunoglobulin infusions in children. Lancet 1993; 342: 1432-33.

tlncludes terminal hospital care and these 2 patients were therefore not included in statistical analysis of number of hospital admissions. Table: Prophylactic effect of subcutaneous gammaglobulin in patients with secondary hypogamma-globulinaemia on a yearly basis before and after institution of treatment

5

preparations intended

End of New Zealand asthma

for intramuscular administration was first described in 1991.4 With this method, serum concentrations of IgG can be adjusted to well within the normal range because the gammaglobulin is almost entirely resorbed from subcutaneous tissue. The method can be used in patients with a previous history of adverse reactions even in a home setting, it requires no presence of a trained partner, it results in a very low incidence of adverse reactions, and it is cheaper than home treatment with intravenous immunoglobulin; it thus represents a preferred form of prophylaxis in adults4 and children’ with primary

hypogammaglobulinaemia. We undertook a retrospective study in 17 patients with secondary hypogammaglobulinaemia due to CLL (n=14), Waldenstrom’s disease (n=2), or lymphoma (n= 1), treated with administered subcutaneously gammaglobulin (Pharmacia, Sweden), given at a dose of about 50 mg/kg weekly. This therapy raised the mean concentration of serum IgG from 3-1 g/L to 5-5 g/L at steady state (after 6 months of therapy) and was associated with a reduction in the number of admissions to hospital due to infection (p<005, Wilcoxon signed rank) and number of courses of antibiotic treatment (p<005, Wilcoxon signed rank) (table). 11 of the 17 patients benefited clinically from the treatment, and the number of days in hospital due to infections was reduced from 272 days (on a 12-month basis in the patient cohort; 2 patients with a terminal disease were excluded from the calculation) to 112 days. No positive effect was noted in the remaining 6 patients. However, infections in these gammaglobulin-treated patients were, in most cases (5 of 6 patients), associated with neutropenia after cytostatic treatment and would therefore most likely not be amenable to prophylaxis with gammaglobulin. The needed to dosage keep patients with hypogammaglobulinaemia free from infections has not been established; previous studies in patients with primary immunodeficiencies of intramuscular gammaglobulin substitution have used

intravenous 25-100 mg/kg bodyweight per week. In our study, patients were given 50 mg/kg bodyweight per week which, although at the lower end of the range, should be sufficient. However, since serum IgG did not reach normal levels, it is likely that even higher doses of gammaglobulin should be given. or

epidemic

and colleagues (Jan 7, p 41) from the Asthma Research group repeat previous that the fall in asthma mortality in New Zealand can be attributed to the changing use of fenoterol. In Crane and colleagues’ first Lancet publication2 they wrote: "... data relating drug sales to mortality trends are of limited value, particularly when management is changing in other ways". Boehringer Ingelheim and its epidemiological advisers believe that this statement is still valid, especially in connection with major advances in outpatient care such as patient education and adequate anti-inflammatory treatment and-by contrast with most other countries-the virtual elimination of in-hospital mortality from asthma. In addition to the well known basic methodological difficulties in ecological studies, the association between fenoterol and mortality is not stable. Pearce and colleagues use market share instead of consumption (number of puffs). Their approach tends to hide the changes in consumption of other &bgr;-agonists. If the sales of fenoterol and other (3-agonists are taken into account, the ascending part of the curve does not suggest a close association with fenoterol. Moreover, the decline in asthma mortality started in 1979, at a time when fenoterol sales were still increasing, which is 10 years before these workers published their first study and 11 years before restrictions for reimbursement came into effect. The adequate use of anti-inflammatory drugs, in particular inhaled corticosteroids, has proved to have profound clinical effects and has led to a ten-fold reduction in asthma mortality.3 The plotting of the sales of inhaled steroids in 100 µg equivalents hides the fact that the decline followed the introduction of adequate doses of inhaled corticosteroids for at-risk patients.’ Higher dose formulations of beclomethasone were marketed for the first time in 1979, just before the start of the first decline. In 1988 and 1989, just before the second steep decline, new high-dose steroid powder formulations were introduced and rapidly assumed a major role in treatment, especially of patients with severe asthma. Pearce and colleagues not only fail to consider all important evidence from New Zealand, but they also fail to SiR-Pearce

Wellington suggestions’

383