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CLINICAL REVIEW: David P D'Cruz Systemic lupus erythematosus BMJ 2006; 332: 890-894 [Full text]

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Fundoscopy in systemic lupus erythematosus

Roger H Armour   (17 April 2006)

Systemic lupus erythematosis – an ophthalmologist's viewpoint

Mohammad T Masoud, Ajmal Rehman   (18 April 2006)

SLE incidence has increased with use of contraceptive and menopausal progesterones and oestrogens

Maurizio Cutolo, Ellen C G Grant   (22 April 2006)

Treatment of cutaneous lupus erythematosus

Susan J Jessop, David Whitelaw   (8 May 2006)

Treatment of systemic lupus erythematosus

David A Whitelaw, Sue Jessop   (8 May 2006)

Systemic lupus erythematosus -an example of unetiological medicine

Nikola Ilankovic   (23 May 2006)

Re: Treatment of systemic lupus erythematosus

Ellen C G Grant   (24 May 2006)

Fundoscopy in systemic lupus erythematosus 17 April 2006
Roger H Armour, Hon. Consultant Surgeon (retired consultant surgeon) Lister Hospital, Stevenage SG1 4AB Send response to journal: Re: Fundoscopy in systemic lupus erythematosus	David D'Cruz says that the key to early diagnosis of systemic lupus erythematosus (SLE) includes a "a complete systems review and examination...". But he should have highlighted the importance of fundoscopy. The ocular fundus is the common meeting place of all systems, and it is here that the living pathology of SLE: cotton wool spots, haemorrhages, and sometimes disc changes, may be seen with an ophthalmoscope. Fundoscopy clinched the diagnosis of SLE in a 14-year-old girl with paraplegia I saw some years ago. It is the single most important part of the examination if severe SLE (or the Hughes antiphospholipid syndrome) is suspected. Competing interests: I am a director and shareholder of Ophthalmos Ltd, a company that is making a lensfree ophthalmoscope
Systemic lupus erythematosis – an ophthalmologist's viewpoint 18 April 2006
Mohammad T Masoud, Senior House Officer, Ophthalmology Stirling Royal Infirmary, Stirling. UK. FK8 2AU, Ajmal Rehman Send response to journal: Re: Systemic lupus erythematosis – an ophthalmologist's viewpoint	Dr D’Cruz’s review article on systemic lupus erythematosis (SLE) is very informative (1). As ophthalmologists, we often come across patients with ophthalmic manifestations of SLE. Keratoconjunctivitis sicca (KCS) or dry eyes is one of the commonest presentations of SLE (2). Grennan found clinical features of KCS in 25 percent and Al-Mayouf in 13 percent of their patients with SLE (3)(4). KCS can be treated by tear substitutes, mucolytic agents and occlusion of the lacrimal puncta. SLE is also known to cause cicatrising conjunctivitis, peripheral ulcerative keratitis and scleritis (5). It is important to note that scleritis associated with SLE is usually a benign and self-limiting condition. This is in contrast to scleritis associated with some of the other systemic vasculitic diseases like Wegner’s granulamotosis which can lead to permenant blindness (6). Retinal vascular lesions are reported to occur in 3 to 29% of SLE cases (7). These include cotton-wool spots, occlusion of central vein or its branches, occlusion of central retinal artery or its branches and extensive peripheral capillary nonperfusion and neovascularization (7)(8). Retinal vascular occlusions in SLE patients have also been found to be associated with the antiphospholipid syndrome. Retinal vascular disease along with optic neuropathy is the major cause of blindness in patients with SLE (9). It is important for physicians to keep in mind the ocular manifestations of SLE when dealing with such patients. Ophthalmic history and examination, especially dilated fundoscopy, can therefore prove very helpful. Ophthalmologists can also play an important role in the diagnosis of patients with SLE, since ocular inflammatory lesions may precede potentially serious extraocular disease. Many hospitals, including ours, run joint ‘Ophthalmology-Medicine Immunology clinics’, where such patients can be treated more efficiently. References: 1 David P D'Cruz. Systemic lupus erythematosus. BMJ 2006;332: 890- 894 (15 April). 2 Arevalo JF, Lowder CY, Muci-Mendoza R. Ocular manifestations of systemic lupus erythematosus. Curr Opin Ophthalmol.2002 Dec;13(6):404-10. 3 Grennan DM, Ferguson M, Williamson J, Mavrikakis M, Dick WC, Buchanan WW. Sjogren's syndrome in SLE: Part I. The frequency of the clinical and subclinical features of Sjogren's syndrome in patients with SLE. N Z Med J. 1977 Oct 26;86(598):374-6. 4 Al-Mayouf SM, Al-Hemidan AI. Ocular manifestations of systemic lupus erythematosus in children. Saudi Med J. 2003 Sep;24(9):964-6. 5 Heiligenhaus A, Dutt JE, Foster CS. Histology and immunopathology of systemic lupus erythematosus affecting the conjunctiva. Eye. 1996;10 ( Pt 4):425-32. 6 Sainz de la Maza M, Foster CS, Jabbur NS. Scleritis associated with systemic vasculitic diseases. Ophthalmology. 1995 Apr;102(4):687-92. 7 Song YH, Kim CG, Kim SD, Kim YY, Choe JY. Systemic lupus erythematosus presenting earlier as retinal vaso-occlusion. Korean J Intern Med. 2001 Sep;16(3):210-3. 8 Ermakova NA, Alekberova ZS, Kosheleva NM, Reshetniak TN. [Characteristics of retinal vascular involvement in systemic lupus erythematosus]. Vestn Oftalmol. 2001 Mar-Apr;117(2):21-4. 9 Giorgi D, Balacco Gabrieli C. Optic neuropathy in systemic lupus erythematosus and antiphospholipid syndrome (APS): clinical features, pathogenesis, review of the literature and proposed ophthalmological criteria for APS diagnosis. Clin Rheumatol. 1999;18(2):124-31. Competing interests: None declared
SLE incidence has increased with use of contraceptive and menopausal progesterones and oestrogens 22 April 2006
Maurizio Cutolo, Professor of Rheumatology and Internal Medicine Research laboratory and Division of Rheumatology, University of Genoa, Italy, Ellen C G Grant Send response to journal: Re: SLE incidence has increased with use of contraceptive and menopausal progesterones and oestrogens	Dr David P D'Cruz writes that the role of exogenous hormones such as the contraceptive pill and hormone replacement therapy (HRT) in exacerbating or precipitating lupus has been controversial.1 In the study from Sanchez-Guerro et al, which claimed to find no increases in disease activity with oral contraceptives, progestin users and progestin/estrogen users had 7 and 3 times more severe disease flares in than users of non- hormonal IUDs.2 The majority of progestin-only patients (30 out of 54) stopped use before 12 months, including for “personal reasons”. However, progestin-dominant oral contraceptives increase monoamine oxidase (MAO) activity in endometrial glands and platelets which relates to depressive mood changes and loss of libido in many women taking low-dose oestrogen contraceptives.3 These adverse effects are often listed misleadingly as “personal reasons” for early discontinuation. The incidence of SLE has increased 9-fold in recent decades and now affects mostly young women in a sex ratio of 9 women to one man.4 In both men and women with SLE tissue aromatase activity increases with large increases in the ratio of mitogenic 16-hydroxyestrogens to 2- hydroxyestrogens metabolites.5 Sex hormones are key regulators of immunity and it seems unwise to recommend further use of progesterones in women with SLE. 1 D’Cruz DP. Systemic erythematosus. BMJ 2006;332:890-894 (15 April), doi:10.1136/bmj.332.7546.890 2 Sanchez-Guerrero J, Uribe AG, Jimenez-Santana L, et al. A trial of contraceptive methods in women with systemic lupus erythematosus. N Engl J Med 2005: 353: 2539-2549. 3 Grant ECG, Pryce Davies J. Effect of oral contraceptives on depressive mood changes and on endometrial monoamine oxidase and phosphatases. BMJ 1968;3:777-80. 4 Grant ECG. Systemic lupus erythematosus. Lancet 2001; 358:586. 5 Cutolo M, Lahita RG. Estrogens and arthritis. Rheumatic Disease Clinics of North America 2005:31:19-27. Competing interests: None declared
Treatment of cutaneous lupus erythematosus 8 May 2006
Susan J Jessop, Consultant dermatologist Groote Schuur Hospital Observatory 7925 South Africa, David Whitelaw Send response to journal: Re: Treatment of cutaneous lupus erythematosus	Dr D'Cruz has given a brief outline of the treatment of cutaneous lupus erythematosus.1 His recommendations are not supported by evidence- based literature. A randomised controlled trial (RCT) has demonstrated the superiority of potent topical steroids over low potency, (weak), topical steroids in discoid lupus erythematosus, (DLE), 2 a finding in alignment with the clinical experience of many dermatologists treating people with DLE. In addition, while there is no RCT-based evidence, existing evidence for the use of methotrexate and thalidomide is better than for topical tacrolimus or pimecrolimus. We have discussed the limited available evidence for the treatment of DLE in a Cochrane systematic review.3 1. D'Cruz David P. Systemic lupus erythematosus. BMJ 2006;332: 890- 894 (15 April). 2. Roenigk HH, Martin JS, Eichorn P, Gilliam JN. Discoid Lupus Erythematosus. Diagnostic features and evaluation of topical corticosteroid therapy. Cutis 1980;25:281-5. 3. Jessop S, Whitelaw D, Jordaan F. Best treatments for discoid lupus erythematosus. Systematic review. Cochrane Library January 2001. Competing interests: None declared
Treatment of systemic lupus erythematosus 8 May 2006
David A Whitelaw, Consultant rheumatologist Tygerberg Hospital Parow Cape Town South Africa, Sue Jessop Send response to journal: Re: Treatment of systemic lupus erythematosus	Dr D.Cruz attempts to cover a wide field and inevitably there are several contentious statements. i) He does not distinguish between arthralgia and arthritis. Paracetamol is generally accepted as most appropriate treatment for arthralgia. However, a significant percentage of patients have active synovitis and require more specific therapy. He unfortunately fails to address this question. ii) The description of treatment of lupus nephritis ignores the subtypes and he chooses to concentrate on Type IV nephritis. The study by Ginzler is difficult to interpret due to their failure to use 'intention to treat' in their analysis. This resulted in a far lower percentage of patients on cyclophosphamide appearing to respond compared to other studies.1,2,3 Some ethnic groups develop more aggressive disease and need to be treated more aggressively.4 The review by Lenz gives a balanced view of the current problems of treating proliferative nephritis in lupus.5 iii) CNS involvement is a difficult area of diagnosis. Any approach to this area should bear the findings of Hanly6 and Spangenberg7 in mind, namely that many symptoms may be due to co-morbidities. A minor point is that several series have failed to find an association between the ACA (Hughes Syndrome) and migraine, and this relationship is currently unresolved.8 iv) The statement that valve disease sometimes progresses rapidly to replacement, applies to only a small percentage of patients. A review from the Mayo Clinic puts this issue in perspective.9 References: 1: Ginzler EM, Dooley MA, Aranow C et al; Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 2005;353: 2219- 28 2: Austin HA, Klippel JH, Balow JE et al : Therapy for lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986; 314: 614-9. 3: Chan TM, Tse KC, Tang CSO Lai KN, Li FK : Long term outcome of patients with diffuse proliferative pulus nephritis treated with prednisolone and oral cyclophosphamide followed by azathioprine. Lupus 2005; 14: 265-272. 4: Bakir AA, Levy PS, Dunea G. The Prognosis of Lupus Nephritis in African -Americans: A Retrospective Analysis. Am J Kidney Dis 1994; 24: 159-171. 5 Lenz O, Fornoni A, Contreras G. Defining the role of mycophenolate mofetil in the treatment of proliferative lupus nephritis. Drugs 2005; 65: 2429-36. 6 : Hanly JG, McCurdy G, Fougere L, Douglas JA, Thompson K. Neuropsychiatric Events in Systemic Lupus Erythematosus: Attribution and Clinical Significance. J Rheumatol 2004: 31; 2156-62. 7 : Spangenberg JJ, Moller AT, Hugo FJ, Halland AM, Whitelaw DA. The nature and prevalence of neuropsychological impairment in patients with systemic lupus erythematosus. Studia Psychologica. 2000: 42; 123-134. 8 : Whitelaw DA, Hugo FJ, Spangenberg JJ. Headaches in patients with Systemic Lupus Erythematosus. A comparative study. Lupus 2004: 7; 501-5. Competing interests: None declared
Systemic lupus erythematosus -an example of unetiological medicine 23 May 2006
Nikola Ilankovic, Professor Belgrade Send response to journal: Re: Systemic lupus erythematosus -an example of unetiological medicine	Unfortunately, the syndromological approach and the symptomatic therapy of consequences (with general or universal drugs, "panacea") without etiological investigations, are the dominant trends in new unetiological, pharmacological medicine. "Systemic lupus erythematosus" and other so called "systemic", "autoimmune" diseases, are the best examples of unetiological medicine... The "explanation" of "autoimmunity" is similar to the "explanation" of "perpetum mobile", without any causes of disease and with application of universal (very dangerous) immunosuppresive therapy, independent from any well known etiological factors (1. Infections-focalosis! and systemic infections: Syphilis or Lues, now so called "Antiphopholipidal syndrome", TBC, Lyme, etc.; 2. Drugs and other chemical supstances, 3. Metabolic disturbances; 4. Physical damages and 5. All other etiological factors which can damage the tissue and provoke autoimmune reactions.) The basic principles in medicine must be furthermore: 1. PRIMUM NON NOCERE 2. THE THERAPY DEPENDS ON CAUSE/CAUSES OF ILLNESS If this basic approach in therapy is impossible, we are working with symptomatic therapy, but with further diagnostic and etiological investigations to try to find any of the causes of illnesses. Competing interests: None declared
Re: Treatment of systemic lupus erythematosus 24 May 2006
Ellen C G Grant, physican and medical gynaecologist Kingston-upon-Thames. KT2 7JU, UK Send response to journal: Re: Re: Treatment of systemic lupus erythematosus	David Whitelaw writes that several series have failed to find an association between the ACA (Hughes Syndrome) and migraine, and this relationship is currently unresolved. However, the study he and his colleagues published reported that 38% of systemic lupus erythematosus (SLE) patients developed migraine headaches with the onset of lupus compared with 6% of the control group of nurses developing migraine on commencing work.1 Exposures to contraceptive or menopausal progesterones and oestrogens are major precipitants of both SLE and migraine.2 As many as 60% of women developed migraine headaches during the first of taking some oral contraceptive pills which matched the number of women with numerous thickened arterioles in otherwise atrophic progestin-treated endometrial biopsy specimens.3 Both headaches and mood changes are important reason for early discontinuation of hormonal contraceptives and the combinations with the greatest angiogenic effect had the highest first year stoppage rate.4 High or low doses of progesterone and progestins can powerfully stimulate angiogenesis.5 However, SLE patients continue to have higher incidences of migraine, thrombosis and psychiatric symptoms even after stopping hormone use, possibly because of uncorrected essential nutrient deficiencies, allergies and impaired immunity. 1 Whitelaw DA, Hugo FJ, Spangenberg JJ. Headaches in patients with Systemic Lupus Erythematosus. A comparative study. Lupus 2004: 7; 501-5. 2 Grant ECG. Systemic lupus erythematosus. Lancet 2001; 358:586. 3 Grant ECG. Relation between headaches from oral contraceptives and development of endometrial arterioles. BMJ 1968; 3: 402-5. 4 Changing oral contraceptives. BMJ 1969; 4: 789-91. 5 Mirkin S, Wong BC, Archer DF. Effect of 17 beta-estradiol, progesterone, synthetic progestins, tibolone, and tibolone metabolites on vascular endothelial growth factor mRNA in breast cancer cells. Fertil Steril 2005; 84: 485-91. Competing interests: None declared