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significantly correlated with both serum phosphate and oral

phosphate intake (/- - 0-70 and 0-73, respectively; p < 0-05). Only 1patient excreted urine that was slightly supersaturated with calciumoxalate, brushite, and apatite. Another child showed

supersaturation with apatite only. There was no correlationbetween phosphate intake and either oxaluria or free energy ofcrystallisation for calcium oxalate, brushite, or apatite.The main difference between our study and that of Reusz et al is

the dose of phosphate, which exceeded 3 g/173 m2 daily in 4 ofReusz and colleagues’ patients. This explanation accounts for thehigher concentrations of urinary oxalate and phosphate that theyfound. These concentrations of urinary oxalate are associated withcalcium oxalate supersaturation and precipitation. As we haveshown, mild hyperoxaluria is not necessarily accompanied byurinary supersaturation with calcium oxalate, especially if calciumexcretion rates are kept within normal limits. However, highurinary phosphate concentrations, which can be expected whenphosphate supplements exceed 2-3 g daily, can lead to urinarysupersaturation with calcium phosphate salts.

Although nephrocalcinosis is a common complication of therapyin X-linked hypophosphataemia,1,3 nephrolithiasis is not. Urinarysaturation has been adopted as a measure of the risk of lithogenesis. 4We suggest that it might be a valuable aid when assessing the risk ofrenal calcification in children with hereditary rickets.

Study Group on Lithiasis,Catamarca 2031,(2000) Rosario SF, Argentina

ARIEL SANCHEZ

ADRIANA GONZ&Aacute;LEZJOS&Eacute; LUIS FERRETTI

Department of Endocrinology,San Lorenzo 876,(2000) Rosario SF, Argentina

AM&Iacute;LCAR MENICHINIHUGO CARRETTO

1. Reusz GS, Latta K, Hoyer PF, et al. Evidence supporting hyperoxaluna as a cause ofnephrocalcinosis in phosphate-treated hypophosphataemic rickets. Lancet 1990;335: 1240-43.

2. Mattos E, Taborda M, Gonz&aacute;lez A, et al. Equil AT: computer program for thecalculation of free energy for crystallization (DGcryst). XXI Congress of theInternational Urological Society, Buenos Aires, 1988: 778.

3. Goodyear PR, Kronick JB, Jequier S, et al Nephrocalcinosis and its relationship totreatment of hereditary rickets. J Pediatr 1987; 111: 700-04.

4. Wilson DM. Clinical and laboratory approaches for evaluation of nephrolithiasis.J Urol 1989; 141: 770-74.

Possible association between toxicepidermal necrolysis and ciprofloxacin

SIR,- Toxic epidermal necrolysis is a rare skin diseasecharacterised by an extensive detachment of the epidermis withsubepidermal blister formation and severe constitutional

symptoms.1.2 It is usually associated with multisystem involvement3and a high mortality between 20% and 66% in the acute phase.2-4Drug reactions are the most frequent cause.2A 72-year-old woman was admitted for a right total hip

replacement because of Paget’s disease affecting her pelvis. She hadbeen a non-insulin dependent diabetic for 10 years on gliclazide.She had been taking naproxen for arthritis for 10 years, and ferrousfumarate and temazepan for many years. She had a history ofallergies to penicillin, co-trimoxazole, and tetracycline. She wasbegun on co-codamol and her other drugs were continued, apartfrom ferrous fumarate. Two days after admission urinary tractinfection was noted and she was given ciprofloxacin 500 mg twicedaily for nine days. Two days after starting ciprofloxacin she had heroperation and at that time received temazepam, morphine,thiopentone, atracurium, isoflurane, nitrous oxide, glycopyrroniumbromide, and, as prophylaxis, erythromycin (which she hadreceived in the past with no problems). She was recommenced onferrous fumarate and discharged home with no complications on thesame drugs as before admission.

She remained well until five days later (seven days after

completing the course of ciprofloxacin) when an itchy, generalisederythematous confluent rash developed on her right leg, chest, andback, with pyrexia, sweating, nausea, and vomiting. She wasgenerally unwell and was readmitted. Haemoglobin was 10.4 g/dl,white cell count 1-5 x 109/1, and platelets 62 x 109/1; she had earlydisseminated intravascular coagulation, and urea was 10-4 mmol/1,bilirubin 49 mmol/1, alkaline phosphatase 198 mmol/1, and

gamma-glutamyl transferase 162 mmol/1. Her rash progressed, with

formation of bulla. She was initially treated with intravenous (iv)ciprofloxacin 200 mg twice daily with later addition of erythromycinfor presumed septicaemia, although subsequent cultures of herblood, urine, right hip aspirate, and bullae fluid showed no growthapart from a late blood culture which grew Candida albicans. She alsoreceived co-codamol, cyclizine, chlorpheniramine, and ranitidine.Her condition deteriorated as her rash became more widespread

with bullous lesions all over which sloughed easily on contact,resulting in skin loss. In addition she had purpura, ecchymoses,conjunctival involvement, throat ulcers, haematemesis, progressiverenal and liver failure, and pancytopenia, and her level ofconsciousness deteriorated. Toxic epidermal necrolysis was

diagnosed. Ciprofloxacin, erythromycin, naproxen, and gliclazidewere discontiuned. She was given iv cefotaxime 1 g thrice daily, ivnetilmicin 80 mg thrice daily, and iv methylprednisolone 250 mgfour times daily. Supportive treatment consisted of barrier nursingon an air fluidised ’Clinitron’ bed, framycetin sulphate cream,platelet infusion, fresh frozen plasma, albumin infusion, fluidreplacement, and ’Cyclimorph’ (Cahnic) for pain.

She did not improve and died eight days after the onset of herillness. Necropsy showed severe epidermal necrosis with

subepidermal separation consistent with drug-induced toxic

epidermal necrolysis, possibly due to ciprofloxacin and associatedwith hepatic necrosis, acute tubular necrosis, aplastic anaemia, andcandidiasis of oropharynx and oesophagus.

Ciprofloxacin is a 4-quinolone antibiotic active against gram-negative and gram-positive bacteria. Serious adverse reactions

reported with ciprofloxacin are rare, with an incidence of 0.6%.5There has been one previous report of toxic epidermal necrolysis tothe Committee of Safety of Medicines and two other cases have beenreported to the drug company (Bayer UK, personal communication).There have been one case of granulocytopenia, four of pancytopenia,and fifteen of leucopenia worldwide (ref 5 and Bayer, personalcommunication). Serious rashes, raised liver function tests, andinterstitial nephritis may arise rarely.s With the use of ciprofloxacinextending to the community, an association between the drug andtoxic epidermal necrolysis should be borne in mind.

Departments of Therapeutics and Pharmacology,Dermatology, and Pathology,

Belfast City Hospital,Belfast BT9 7BL, UK

TONY C. K. THAMGRACE ALLENDOROTHY HAYESBRENDAN MCGRADY

JAMES G. RIDDELL

1. Lyell A. Toxic epidermal necrolysis: an eruption resembling scalding of the skin. Br JDermatol 1956; 68: 355-61.

2. Pye RJ. Toxic epidermal necrolysis. In. Rook E, Wilkinson DS, Eblilng FJG,Champion RH, Burton JL, eds. Textbook of dermatology, vol 2, 4th ed. Oxford:Blackwell Scientific, 1986: 1658-59.

3. Revuz J, Penso D, Roujeau J-C, et al. Toxic epidermal necrolysis: clinical findings andprognosis factors in 87 patients. Arch Dermatol 1987; 123: 1160-65.

4. Fritsch PO, Elias PM Toxic epidermal necrolysis. In: Fitzpatrick TB, Eisen AZ,Wolff K, Freedberg IM, Austen KF, eds. Dermatology in general medicine. NewYork: McGraw Hill, 1987: 559-63.

5 Schacht P, Arcieri G, Hullmann R. Safety of oral ciprofloxacin. Am J Med 1989; 87(suppl 5A):98-102.

Mucosal humidification

SIR,&mdash;I often see reference to the benefits of mucosalhumidification in treatment of upper-respiratory-tract problems,an example being a paper in your July 13 issue (p 96). I am alsoreminded of my own non-compliance when my doctor tells me tokeep my head over a pot of hot water for 20 minutes several times aday. In rebellion against such a regimen I developed an alternative.Take a strip (60 x 5 cm) of porous material-I cut up a worn-outtee-shirt, which strikes a good balance between water retention andbreathability-and tie it round your head to cover the nose and keepit wet. I now get a good 10 minutes of mucosal humidification everyday in the shower, and if my chronic sinus acts up I can sit with a cupof hot water, simply moistening the strip regularly. That way I canread, work, or carry out any other reasonable activity, and notsimply stare at the bottom of a pot of hot water. I have been able toget, without annoyance, mucous-loosening treatment timesmeasured in hours, not minutes.

P 0 Box 42493,Nairobi, Kenya GORDON W. BROWN