Fig 2-Cutaneous KS lesions examined by PCR and concomitant immunoreactivityfor HPV-16-specific E7 protein. Left strong nuclear immunoreactivity in dermal spindle-shaped cells from Right. absence of immunoreactivity in PCR-negative case, x 200

attention. Nonetheless, this letter and the article in this issue will, we hope, prompt colleagues to consider papillomaviruses as possible KS agents. Dr J. T.

Headington kindly reviewed slides and the text.

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA

Departments of Microbiology and Dermatology, New York University School of Medicine 1






Lowy DR, Ju WD. Pathophysiology ofcutaneous viral infections: papillomavirus. In: Soter NA, Baden HP, eds. Pathophysiology of dermatologic diseases. New York:

McGraw-Hill, 1991 441-52. RJ, Jenson AB, Sinclair CF, Lancaster WD. Detection of human papillomavirus by immunohistochemistry. In: DeLellis RA, ed. Advances in immunohistochemistry. New York. Masson, 1984: 201-21. 3 Nickoloff BJ. The human progenitor cell antigen (CD34) is localized on endothelial cells, dermal dendritic cells, and perifollicular cells in formalin-fixed normal skin, and on proliferating endothelial cells and stromal spindle-shaped cells m Kaposi’s sarcoma. Arch Dermatol 1991; 127: 523-29 4. Lacey M, Alpert S, Hanahan D Bovine papillomavirus genome elicits skin tumours in transgenic mice. Nature 1986; 332: 609-12. 5. Nickoloff BJ, Griffiths CEM The spindle-shaped cells m cutaneous Kaposi’s sarcoma: histologic stimulators include factor XIIIa dermal dendrocytes. Am J Pathol 1989; 135: 793-800. 6 Rutgers JF, Wieczorek R, Bonetti F, et al The expression of endothelial cell surface antigens by AIDS-associated Kaposi’s sarcoma: evidence for a vascular endothelial origin Am J Pathol 1986; 122: 493-99 7 Nickoloff BJ, Griffiths CEM. Factor XIIIa-appearing dermal dendrocytes in AIDS-associated cutaneous Kaposi’s sarcoma. Science 1989; 243: 1736-37. 8 Mahoney SE, Duvic M, Nickoloff BJ, et al. Human immunodeficiency virus (HIV) transcripts identified m HIV-related psoriasis and Kaposi’s sarcoma lesions. J Clin Invest 1991; 88: 174-85. 9 Beral V, Peterman TA, Berkelman RL, Jaffe HW. Kaposi’s sarcoma among persons with AIDS. a sexually transmitted infection? Lancet 1991; 335: 123-28. 10. Friedman-Kien AE, Saltzman BR, Cao Y, et al Kaposi’s sarcoma in HIV-negative 2 Kurman

homosexual men. Lancet 1991, 335: 168-69.

Thalidomide for systemic lupus

erythematosus SiR,—Treatment for systemic lupus erythematosus (SLE) is largely symptomatic, with antimalarials, glucocorticoids, and immunosuppressive drugs.’ Thalidomide has proved successful in the treatment of chronic discoid lupus erythematosus (CDLE),2 antimalarial-resistant CDLE,3 subacute cutaneous lupus

PCR-positive case (brown chronogen reaction product),



erythematosus,4 and lupus erythematosus profundus.5 However, thalidomide treatment of SLE has not yet been investigated in detail.’ We report 3 patients with SLE, confirmed according to the American Rheumatism Association 1982 criteria. Patient 1-A 30-year-old woman had progressive acute SLE for 6 years (onset 1985) with multivisceral features-cutaneous, articular, muscular, and neurological (severe polyneuropathy of the lower limbs)—and impure renal nephrotic syndrome with segmental and focal glomerulonephritis, pancytopenia, and Raynaud’s syndrome. Immunological screening showed positive antinuclear antibodies (ANA), anti-DNA-antibodies (titre 1/280), anti-smooth muscle (SM) antibodies, and hypocomplementaemia. Various treatments were instituted successively: corticosteroid (per os or bolus injection) with corticodependence (25 mg per day), cyclophosphamide, plasmapheresis, and cyclosporin. She had severe infectious episodes with renal deterioration with these treatments. 3! years after onset of SLE (July, 1988) thalidomide (100 mg daily) combined with glucocorticoids (40 mg daily) were instituted. Tolerance of this treatment was adequate with no side-effects. Clinical improvement, with appreciably reduced skin and articular features and without neuropathological deterioration, led to a progressive decrease in glucocorticoid dose. Thalidomide therapy was maintained for 2 years at daily doses of 25-100 mg. No changes in immunological indices (ANA, anti-DNA antibodies, and complement) were seen. The patient has since been kept on maintenance corticosteroid therapy. Patient 2-A 27-year-old woman had SLE for 5 years (onset 1986) with skin lesions and articular features (but no other visceral symptoms) and immunological disorders: ANA (1/640), anti-DNA antibodies, and anti-SM antibodies. Initial treatment with synthetic antimalarials failed, and thalidomide (200 mg daily) was begun in March, 1988. Cutaneous features almost completely disappeared after 3 months of treatment and articular symptoms decreased slightly. After 6 months on thalidomide she had serious drowsiness, despite a reduction in dose. Treatment was stopped in November, 1988, which led to recrudescence of skin and articular features. General corticosteroid therapy was then instituted with adequate

therapeutic response. Patient 3-A 26-year-old woman had SLE for 5 years (onset 1986) with skin lesions and articular features and immunological disorders: ANA (1/1024), anti-SM antibodies, and hypocomplementaemia. General corticosteroid therapy after initial



with antimalarials failed. 6 months

later, she became

corticodependent and thalidomide (100 mg daily) was begun. She tolerated this drug well. There was striking improvement in skin and articular features after 1 month of treatment. The thalidomide dose was therefore lowered to 25-50 mg daily, and she was clinically stable for 2 years with no changes in immunological indices. Signs of peripheral sensitive neuropathy and drowsiness led to discontinuation of thalidomide, with a consequent relapse of skin and articular features. Complete remission of all neurological symptoms, confirmed by electrophysiological screening, was seen after 4 months. Thalidomide was reinstituted (100 mg daily) under close neurological observation, with impromvement of skin lesions and articular features. In all 3 patients a good clinical response of cutaneous and articular symptoms to thalidomide was seen within the first month of treatment, being greatest after 3-4 months. Moreover, in corticodependence, doses were lowered substantially by instituting thalidomide therapy combined with glucocorticoids. Despite the low doses, drowsiness was reported by 2 patients, leading to discontinuation of treatment in 1, and sensitive neuropathy was seen in 1 case, but this disappeared 4 months after stopping treatment. Nevertheless we believe that thalidomide treatment at moderate doses combined with glucocorticoids, under strict contraceptive measures, is helpful for SLE because it improves cutaneous and articular control, and steroid use can be reduced. Although thalidomide probably has an immunomodulator role, its mode of action has not yet been established? D. BESSIS B. GUILLOT S. MONPOINT Service of Dermatology-Phlebology, M. DANDURAND Hôpital Saint-Charles, 34059 Montpellier, France J. J. GUILHOU 1. Kahn MF. The treatment of lupus in the 1990s. Clin Exp Rheumatol 1990; 8 (suppl 5): 45-49. 2. Barba-Rubio J, Franco-Gonzales F. Lupus eritematoso fijo (su tratamiento con talidomida). Biomed Pharmacother 1990, 44: 199-204. 3. Knop J, Bonsmann G, Happle R, et al. Thalidomide in the treatment of sixty cases of chronic discoid lupus erythematosus. Br J Dermatol 1983; 108: 461-66. 4. Naafs B, Bakkers EJM, Flintermann J, Faber WR. Thalidomide treatment of subacute cutaneous lupus erythematosus. Br J Dermatol 1982; 107: 83-86. 5. Knop J, Happle R, Vakilzadech F, Macher E. Treatment of lupus erythematosus profundus with thalidomide. Arch Dermatol Res 1981; 270: 229. 6. Naafs B, Faber WR. Thalidomide therapy: an open trial. Int J Dermatol 1985; 24: 131-34. 7. Heney D, Bailey CC, Lewis IJ. Thalidomide in the treatment of graft-versus-host disease. Biomed Pharmacother 1990; 44: 199-204.


low-dose-aspirin-induced gastropathy

SiR,—The incidence of pregnancy-induced hypertension (PIH) has been shown to be decreased in women given low-dose aspirin who are deemed at risk for PIH.l,2 Large studies, such as the Collaborative Low-dose Aspirin Study in Pregnancy (CLASP), have been initiated. However, there are concerns about the safety of aspirin ingestion in pregnancy. 3,4 We report a possible complication of low-dose aspirin administration. A 30-year-old primiparous non-smoker attended antenatal clinic at 10 weeks’ gestation with blood pressure 115/75 mm Hg. She was taking no drugs, and had no family or personal history of hypertension or peptic ulceration. At 23 weeks’ her blood pressure was 160/110 mm Hg. She was symptom free with normal fundoscopy and no oedema, hyperreflexia, or proteinuria. Platelet count and serum assays of renal and liver function were normal. Low-dose aspirin (75 mg once daily) and methyldopa were started. At 29 weeks’ gestation she presented with epigastric pain and was treated with metoclopramide. Six hours later she vomited 400 ml fresh red blood and her blood pressure fell to 100/60 mm Hg. Melaena was noted. Haemoglobin concentration fell from 112 g/dl to 94 g/dl. Two units of blood were transfused and intravenous ranitidine was given. Persistent fetal heart rate decelerations occurred and a caesarean section was done. A live 680 g baby girl was delivered. At gastroscopy a small superficial gastric ulcer and mild gastritis were seen. She was prescribed cimetidine and alginic acid and recovered uneventfully.

A 28-year-old non-pregnant nulliparous woman in a study of cyclooxygenase-dependent platelet reactivity took low-dose aspirin (60 mg once daily) for ten days. She was taking no other drug and had no history of peptic ulceration. The first course was uncomplicated. However, when this was repeated 12 months later, she presented with melaena 2 weeks after aspirin ingestion. At gastroscopy a healing duodenal ulcer was noted. She was given a

of cimetidine and had no further melaena. Gastrointestinal tract mucosal damage is a side-effect of all non-steroidal, anti-inflammatory drugs (NSAIDs), and may determine whether administration of low-dose aspirin is appropriate. Endoscopy in patients taking aspirin reveals lesions ranging from simple erythema to ulceration.sIndices for recognising NSAID gastropathy and classic peptic ulcer disease differ. NSAID gastropathy has a mainly antral or prepyloric localisation, is found in female NSAID users, and is presumed to be due to NSAID-induced depletion of cytoprotective prostaglandins.5 However, as in our patients, it is often difficult to ascertain whether aspirin intake exacerbates a pre-existing ulcer or causes one to develop de novo. Methods of reducing possible side-effects of low-dose aspirin should be considered. Entericcoated formulations, suppositories, and pro-drugs offer little advantage, since parenteral and rectal administration of NSAIDs do not spare the stomach.6 Low-dose aspirin therapy should possibly be contraindicated in those at high risk of peptic ulceration, such as smokers or those with a family or previous history of peptic ulceration. Alternatively, low-dose aspirin administration could be restricted to women deemed, on the basis of effective screening, to be at high risk of PIH. No suitable screening test exists, but techniques such as platelet angiotensin-11 binding estimation have considerable potential.7 course

Rosie Maternity Hospital, Cambridge CB2 2NQ, UK


Plymouth General Hospital, Plymouth


M, Uzan S, Donsimoni R, Colau JC. Prevention of pre-eclampsia by early antiplatelet therapy. Lancet 1985; i: 840-42. 2. Wallenburg HCS, Dekker GA, Makovitz JW, Rotmans P. Low-dose aspirin prevents pregnancy-induced hypertension and pre-eclampsia in angiotensin sensitive primigravidae. Lancet 1986; i: 1-3. 3. McNeil J. The possible teratogenic effect of salicylate on the developing fetus: bnef summaries of eight suggested cases. Clin Paediatr 1973; 12: 347-50. 4. Slone D, Siskind V, Heineman OP, Manson RR, Kaufman DW, Shapiro S. Aspirin and congenital malformations. Lancet 1976; i: 1373-75. 5. Collins E, Turner G. Maternal effects of regular salicylate ingestion in pregnancy. 1. Beaufils

Lancet 1975; ii: 335-38. 6. Hansen T, Matzen P, Madsen P. Endoscopic evaluation of the effects of indomethacin capsules and suppositories on the gastric mucosa in rheumatoid patients.

J Rheumatol 1984; 11: 484-87. 7. Baker PN, Broughton Pipkin FB, Symonds EM. Platelet angiotensin II binding sites in normotensive and hypertensive pregnancy. Br J Obstet Gynaecol 1991, 98: 436-40.

pH in critically ill patients

Gastric intramucosal

SiR,—Attention to regional oxygen transport is now recognised important in the resuscitation of critically ill patients, and the measurement of splanchnic hypoperfusion by tonometry (gastric intramucosal pH, pHi) seems to be a useful prognostic index.l.2 Dr Gutierrez and colleagues (Jan 25, p 195) make a valiant effort to address the very important issue of whether manipulation of pHi can alter outcome. There are, however, some important points that as very

should be raised. The overall intensive-care unit (ICU) mortality of all their patients (APACHE II score 15-25 points) was 50%, and for the controls was 58% against a predicted mortality of 40%. The mortality of an equivalent population in our unit is 20%. These differences may in part be related to different levels of intervention. In the update of Cullen’s therapeutic intervention scoring system (TISS),3 patients with a mean daily score of 40 points or more were described as highly dependent, needing one nurse per patient. Patients with a TISS of less than 20 points were thought to need nursing on a 1 nurse to 4 patients basis, and in Gutierrez and colleagues’ study most patients were in this latter category, suggesting a low level of intervention for their APACHE II score.

Thalidomide for systemic lupus erythematosus.

549 Fig 2-Cutaneous KS lesions examined by PCR and concomitant immunoreactivityfor HPV-16-specific E7 protein. Left strong nuclear immunoreactivity i...
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