Professional Documents
Culture Documents
DOI 10.1007/s11096-014-9966-1
REVIEW ARTICLE
Received: 22 October 2013 / Accepted: 27 May 2014 / Published online: 2 July 2014
Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014
M. Al Hussaini (&)
Department of Pharmaceutical Sciences,
College of Health Sciences, Public Authority for Applied
Education and Training (PAAET), Kuwait, Kuwait
e-mail: ma.alhussaini@hotmail.com
E. I. Hammouda
Pharmacy Department, Tawam Hospital in Affiliation with John
Hopkins Medicine, Al Ain, United Arab Emirates
A. E. Hammouda
Faculty of Pharmacy, German University of Cairo, Cairo, Egypt
123
685
Impact on Practice
Sun exposure
Introduction
Systemic lupus erythematosus (SLE) or lupus is a chronic,
progressive, autoimmune disorder that affects multiple
organ systems, with a broad range of clinical and laboratory manifestations [13]. The term lupus means wolf in
Latin and is named as such due to facial lesions found in
the disease process that are reminiscent of a wolfs bite [4].
Methods
Data source
A PubMed search of English language using a combination
of words: elderly, systemic lupus erythematosus, late onset
systemic lupus erythematosus, etiology, screening, diagnosis, or treatment to identify original studies, guidelines,
and reviews on systemic lupus erythematosus, SLE, late
onset systemic lupus erythematosus published between
2000 and present.
Genetic influence
Smoking
Female hormones
Virus exposure
(e.g. EpsteinBarr virus)
Immunizations
Stress
Diet
Source: Refs. [1, 2, 58]
Data synthesis
The literature included guidelines and considerations for
the etiology, diagnosis, screening, and management of
systemic lupus erythematosus, late onset systemic lupus
erythematosus.
Results
Etiology
While the etiology is unknown, there are several factors
associated with the development of SLE (Table 1) [1, 2, 5
8]. Unexplainably, SLE patients do not clear apoptotic cells
appropriately [2, 9]. These cells release auto-antigens that
may help drive the defective immune process [9]. The
complex interaction between environment and immunologic factors in genetically susceptible individuals leads to
continued deregulation of the innate and adaptive immune
pathways [1, 7, 1012]. Autoantibodies often form long
before clinical manifestations result in chronic, widespread
tissue and organ damage [2, 6, 13, 14]. Patients with SLE
experience acute exacerbations and remissions resulting in
protean clinical and serologic manifestations [15, 16].
Systemic lupus erythematosus may develop as a result of
exposure to medications. It is estimated that 10 % of
patients diagnosed with SLE may have drug induced lupus,
and over 38 drugs (Table 2) have been implicated in the
disease development [7, 15, 1720]. However, most cases
have been associated with these three:
Procainamide
Hydralazine
Quinidine.
Epidemiology
123
686
Very low
Low to moderate
High risk
Antiarrhythmics
Disopyramide, propafenone
Quinidine
Procainamide
Antimicrobials/antibiotics
Nitrofurantoin
Isoniazid, minocycline
Anticonvulsants
Carbamazepine
Antihypertensives
Captopril, methyldopa,
acebutolol
Anti-inflammatories
Phenylbutazone
Sulfasalazine, D-penicillamine
Antipsychotics
Chlorpromazine
Antithyroids
Miscellaneous
Hydralazine
Propylthiouracil
Lovastatin, levodopa, aminoglutethimide, alpha-interferon,
timolol eye drops
123
687
Table 4 American College of Rheumatology criteria for diagnosis of
SLE
1. Malar rash: butterfly shaped rash over the nose and cheeks; can
be flat or raised
Physical findings
Malar rash
Pulmonary manifestations
Photosensitivity
Serositis
Arthritis
Pericarditis
Alopecia
Pleurisy
Sjogrens syndrome
Purpura/cutaneous vasculitis
Raynauds phenomenon
Neuropsychiatric
manifestations
Nephritis/Nephrotic syndrome
Hematologic derangements
Serological findings
Increased frequency of antiRNP antibodies and antismantibodies
Low CH50
Anti-RNP antibodies anti-ribonucleoprotein, Anti-Sm antibodies antiSmith antibodies, CH50 50 % hemolytic complement, RF rheumatoid
factor, ANA antinuclear antibodies, Anti-La/SSB anti-La/Sjogren
syndrome type B, Anti-Ro/SSB anti-Ro/Sjogren syndrome type B
Discussion
Treatment
Non-pharmacotherapy
Both the ACR and EULAR recommend non-pharmacologic treatment in the management of SLE. Patients should
123
688
Mild SLE
Antimalarials
Antimalarials
(hydroxychloroquine)
Glucocorticoids
Nonsteroidal anti-inflammatory
drugs (used judiciously)
Immunosuppressive agents
(azathioprine, mycophenolate, and
methotrexate)
Lupus nephritis
Adverse effects
Monitoring
NSAIDs
Gastrointestinal
bleeding, hepatic
toxicity, renal
toxicity,
hypertension
CBC, creatinine,
AST, ALT, blood
pressure, monitor
for bleeding
Glucocorticoids
Hypertension,
hyperglycemia,
hyperlipidemia,
hypokalemia,
osteoporosis,
cataracts, fluid
retention, glaucoma,
infections
Blood pressure,
cholesterol,
glucose,
potassium, bone
mineral density
Hydroxychloroquine
Fundoscopic and
visual fields, visual
changes
Azathioprine
GI side effects,
infections,
Myelosuppression,
hepatotoxicity,
lymphoproliferative
disorders
CBC, differential
and platelet count,
AST or ALT
Cyclophosphamide
Myelosuppression,
malignancy,
hemorrhagic cystitis,
immunosuppression,
severe infections,
nausea, vomiting,
reversible hair loss
CBC, differential
and platelet count,
urinalysis
Methotrexate
Myelosuppression,
hepatic toxicity,
pulmonary infiltrates
or fibrosis, stomatitis
CBC, hepatitis B
and C serology in
high risk patients,
AST, albumin,
bilirubin,
creatinine, chest
radiograph
Mycophenolate
Anemia, leukopenia,
thrombocytopenia,
infections, diarrhea,
pancreatitis
CBC, differential
and platelet count
Belimumab
Infections,
bradycardia,
hypotension,
depression,
leukopenia
CBC, differential
and platelet count
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve arthralgia, inflammation, serositis,
and fever in patients with SLE. They can be used with or
without low doses of steroids or antimalarial agents [40,
44, 45]. NSAIDs inhibit the production of cyclooxygenase1 (COX-1) and cyclooxygenase-2 (COX-2) [51]. The
inhibition of COX-1decreases the production of
123
689
123
690
NSAIDs
Glucocorticoids
Hydroxychloroquine
Azathioprine
Cyclophosphamide
Mycophenolate
Belimumab
123
Conclusion
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder, the exact etiology of which is unknown.
SLE predominately affects younger women; however, it is
reported to occur in up to 20 % of patients 50 years or
older. In patients with SLE, nearly every system in the
body is affected with varying degrees of severity ranging
from subclinical to fatal.
The hallmark feature of SLE is the production of autoantibodies directed primarily against nuclear antigens, but
also against cytoplasmic components of cells. The diagnosis of SLE is based on criteria set by the American
College of Rheumatology. Management is individualized
and depends on presenting symptoms and reducing the
likelihood of permanent damage to organs and tissues.
Conflicts of interest All authors stated that there is no conflict of
interest in this study.
References
1. Agmon-Levin N, Blank M, Paz Z, Shoenfeld Y. Molecular
mimicry
in
systemic
lupus
erythematosus.
Lupus.
2009;18:11815.
2. DCruz D, Khamashta M, Hughes G. Systemic lupus erythematosus. Lancet. 2007;369:58796.
3. Porth C, Matfin G. Pathophysiology: concepts of altered health
states. 8th ed. Philadelphia: Wolters Kluwer Health/Lippincott
Williams & Wilkins; 2009.
4. Boltzer JW. Systemic lupus erythematosus. I. Historical aspects.
MD State Med J. 1983;32:43941.
5. Schur PH, Gladman DD. Overview of the clinical manifestations
of systemic lupus erythematosus in adults. In: Basow DS, editor.
Uptodate. MA: Waltham; 2012.
6. Alarcon-Riquelme ME. The genetics of systemic lupus erythematosus. J Autoimmun. 2005;25:468.
7. Bernknopf A, Rowley K, Bailey T. A review of systemic lupus
erythematosus and current treatment options. Formulary.
2011;46:17894.
8. Soldevilla H, Briones S, Navarra S. Systemic lupus erythematosus following HPV immunization or infection. Lupus.
2012;21:15861.
9. Bilj M, Reefman E, Horst G, Limburg PC, Kallenberg CG.
Reduced uptake of apoptotic cells by macrophages in systemic
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
691
32. Bourre-Tessier J, Huynh T, Clarke A, Bernatsky S, Joseph L,
Belisle P, et al. Features associated with cardiac abnormalities in
systemic lupus erythematosus. Lupus. 2011;20:151825.
33. El-Magadmi M, Bodill H, Ahmad Y, Durrington PN, Mackness
M, Walker M, et al. Systemic lupus erythematosus an independent risk factor for endothelial dysfunction in women. Circulation. 2004;110:399404.
34. Adhikari T, Piatti A, Luggen M. Cognitive dysfunction in SLE:
development of a screening tool. Lupus. 2011;20:11426.
35. Auerbach C, Beckerman N. What social workers in health care
should know about lupus: a structural equation model. Health Soc
Work. 2011;36:26978.
36. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield
NF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25:12717.
37. Smith E, Shmerling R. The American College of Rheumatology
criteria for the classification of systemic lupus erythematosus:
strengths, weaknesses, and opportunities for improvement.
Lupus. 1999;8:58695.
38. Egner W. The use of laboratory tests in the diagnosis of SLE.
J Clin Pathol. 2000;53:42432.
39. Hull C. Systemic lupus erythematosus: a clinical review. Clin
Rev. 2010;20:1823.
40. Kalunian K, Merrill JT. New directions in the treatment of systemic lupus erythematosus. Curr Med Res Opin. 2009;6:150114.
41. Common symptoms of lupus. Lupus Foundation of America 2012.
http://www.lupus.org/webmodules/webarticlesnet/templates/new_
learndiagnosing.aspx?articleid=2241&zoneid=524. Accessed 9
May 2012.
42. Ginzler E. Systemic lupus erythematosus (Lupus), American
College of Rheumatology Patient Fact Sheet, 2012. http://www.
rheumatology.org/practice/clinical/patients/diseases_and_conditions/
lupus.asp. Updated Feb 2013.
43. Gladman DD, Urowitz MB, Esdaile JM, Hahn H, Kippel J, Lahita
R, et al. Guidelines for referral and management of systemic
lupus erythematosus in adults. Arthritis Rheum. 1999;9:178596.
44. Bertsias G, Loannidis JP, Boletis J, Bombardieri S, Cervera R,
Dostal C, et al. EULAR recommendations for the management of
systemic lupus erythematosus. Report of a task force of the
EULAR standing committee for international clinical studies
including therapeutics. Ann Rheum Dis. 2008;67:195205.
45. Amissah-Arthur MB, Gordon C. Contemporary treatment of
systemic lupus erythematosus: an update for clinicians. Ther Adv
Chronic Dis. 2010;1:16375.
46. The Medical Letter Volume 10 (Issue15) March 2012.
47. The Medical Letter Volume 53 (Issue 1366) June 2011.
48. Mycophenolatemofetil capsules and tablets. Pennington, NJ:
Zydus Pharmaceuticals USA,Inc; 2011 April.
49. Ruiz-Irastorza G, Ramos-Casals M, Brito-Zeron P, Khamashta
MA. Clinical efficacy and side effects of antimalarials in systemic
lupus erythematosus: a systemic review. Ann Rheum Dis.
2010;69:208.
50. Mazzoni D, Cicognani E. Social support and health in patients
with systemic lupus erythematosus: a literature review. Lupus.
2011;20:111725.
51. Sostres C, Gargallo CJ, Arroyo MT. Adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs)
on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol.
2010;24:12132.
52. Lander SA, Wallace DJ, Weisman MH. Celecoxib for systemic
lupus erythematosus: case series and literature review of the use
of NSAIDs in SLE. Lupus. 2002;11:3407.
53. Horizon AA, Wallace DJ. Risk: benefit ratio of nonsteroidal antiinflammatory drugs in systemic lupus erythematosus. Expert
Opin Drug Saf. 2004;3:2738.
123
692
54. Scheiman JM, Hindley CES. Strategies to optimize treatment
with NSAIDs in patients at risk for gastrointestinal and cardiovascular adverse events. Clin Ther. 2010;32:66777.
55. Tam LS, Gladman DD, Hallett DC, Rahman P, Urowitz MB.
Effect of antimalarial agents on the fasting lipid profile in systemic lupus erythematosus. J Rheumatol. 2000;9:21425.
56. Kuznik A, Bencina M, Svajger U, Jeras M, Rozman B, Jerala R.
Mechanism of endosomal TLR inhibition by antimalarial drugs
and imidazoquinolines. J Immunol. 2011;186:111.
57. Fortin PR, Abrahamowicz M, Ferland D, Lacaille D, Smith CD,
Zummer M, et al. Steroid-sparing effects of methotrexate in
systemic lupus erythematosus: a double blind, randomized, placebo-controlled trial. Arthritis Rheum. 2008;59:1796804.
58. Islam N, Hossain M, Haq SA, Alam MN, Peter M, Klooster T,
et al. Efficacy and safety of methotrexate in articular and cutaneous manifestations of systemic lupus erythematosus. Int J
Rheum Dis. 2012;15:628.
59. Shum K, Askanase A. Treatment for lupus nephritis. Curr
Rheumatol Rep. 2011;13:28390.
60. Popescu A, Kao AH. Neuropsychiatric systemic lupus. Erythematosus. Curr Neuropharmacol. 2011;9:44957.
61. Kamanamool N, McEvoy M, Attia J, Ingsathit A, Ngamjanyaporn P, Thakkinstian A. Efficacy and adverse events of mycophenolate mofetil versus cyclophosphamide for induction therapy
of lupus nephritis. Medicine. 2010;89:22735.
62. Dooley MA, Jayne D, Ginzler EM, Isenberg D, Olsen NJ, Wofsy
D, et al. Mycophenolate versus azathioprine as maintenance
therapy for lupus nephritis. N Engl J Med. 2011;365:188695.
123