History

Fact Explanation
Introduction Systemic Lupus Erythematosus is an autoimmune connective tissue disorder. This is the commonest connective tissue disorder which affects multi-systems. Majority (90%) of patients are women in child bearing ages But this can affect both sexes in all ages. the prevalence is around 15-50: 100 000. In this condition Various antigentc stimulation causes wide spectrum of antibody production following B and T cell activation. The exact triggering factors for autoantibody production is unknown. Following this abnormal immune response. Antibodies or antigen-antibody complexes deposition in various organs causes influx of neutrophils and lymphocytes inducing inflammatory reaction. Ongoing same reactions finally leads to permanent organ damage[1][2].
Fever, weight loss and other constitutional symptoms like malaise, lethargy, fatiguability These symptoms are common during exacerbation due to increased metabolic activity. But these features are not related to the severity of disease activity or complications[3][4].
Joint pain Joint involvement is the main complain and this can be seen in more then 90% of patients. patient will complain of bilateral symmetrical small joint pain with mild morning stiffness. It can be a migratory arthralgia. Some times there will be swelling as well. Rarely there will be pain in major joints. these patients are at risk of developing aseptic necrosis of the hip/ knee as a rare complication of the disease or following the treatment with corticosteroids[5][6][7].
development of severe pain and bluish discoloration over tip of fingers after exposure to cool water. This called Raynaud’s phenomenon. These symptoms occur following vasculitis. These symptoms commonly associated with arthralgia or arthritis[8][9].
Muscle pain and weakness around 50% of patients can develop myalgia but only few patients develop myositis[6][10].
Skin rash ( may be painful/ pruritic) eruthematous rash on the cheeks aross the nasal bridge (butterfly rash). purpura and urticarial rash over the tip of the fingers and nail folds. These are caused by vasculitis (vasculitic rash). there will be other skin changes like Livedo reticularis and periungual erythema. Patient may also develop palmar and plantar rashes. Patients may develop a erythematous rash in face with well defined margins. there plques can ultimately lead to scarring and pigmentations (Discoid rash). In Subacute cutaneous lupus erythematosus, there is a migratory, non-scarring, papulosquamous/ annular rash[11][12].
alopecia Patients with disoid lupus, commonly developed scarred alopecia causing permanent skin loss (following discoid rash over the scalp)[13][14].
generalized body swelling, reduced urine output, haematuria/ frothy urine. Patients with renal involvement can develop these features of renal impairment. Thought histological changes of glomerulonephritis are occur in majority of patients with SLE only few will presennt with clinical symptoms[15][16].
Difficulty in breathing, pleuritic type chest pain, Patient will develop chest pain and difficulty in breathing following Pneumonitis, atelectasis. Patients also commonly develop bilateral exudative pleural effusions following pleuritis. With these lung manifestations there will reduction of lung volumes (shrinking lung syndrome). Rarely lung fibrosis can occur with Systemic Lupus Erythematosus. 50% people will have lung involvement. Intrapulmonary haemorrhages (due to vasculitis) can cause life threatening conditions[17][18].
chest pain, palpitation, dizziness cardiac involvement can be seen in 25% of cases. Pericarditis with pericardial effusion, myocaditis causing arrhythmias, valve lesions with cardiomyopathy, arterial and venous thrombosis following vasculitis can be seen. These patients are at risk of developing strokes and ischemic heart diseases[19][20].
features of hypoperfusion/ ischemia following vasculitis Due to the cardiac involvement and with the possibility of arterial and venous thrombus formation with vasculitis, patients are at risk of developing organ hypoperfusion. Eg: Brain strokes can occur giving features of paralysis, paresthesia and cranial nerve palsy. In spinal cord, features of infarction like limb paralysis, paresthesia, bladder/ bowel dysfunction. In bones, ischemic pain at site of the joint/back pain and fractures following long bone infarction can be seen. Myocardial infarctions can occur following hypoperfusion of the myocardium( chest pain, difficulty in breathing, dizziness). In lungs there will be shortness of breath and pleuritic type chest pain. In mesentry, acute abdominal pain will be the presentation. In digits, painful fingers and toes with small bone infarction. In kidneys infarction of medulla with papillary necrosis may lead to fail in concentrating urine causing high urine out put, dehydration and nocturnal enuresis. Chronic liver failure with micro infarction causing loss of appetite, yellowish discoloration of eyes. Splenic infarction leads to recurrent infections like upper/ lower respiratory tract infections and diarrheal illnessess[21][22].
seizures, alteration in mental status, headache, poor concentration 60% of patient will develop cerebral lupus. theses patients are at risk of developing epilepsy, migraines, poor concentration, cerebellar ataxia, aseptic meningitis, cranial nerve lesions, cerebrovascular disease and polyneuropathy. Also there can be visual hallucinations, chorea, organic psychosis[23][24].
eye pain, redness of the eyes and visual impairment With vasculitis there will be retinal infarctions leading to hard exudates, and haemorrhages. Also patients can develop episcleritis, conjunctivitis, optic neuritis and Sjögren’s syndrome (dry eyes and mucous menmbranes). Though several eye complications can occur, blindness is very rare[25][26].
yellowish discoloration of the eyes, oral ulcers, sudden onset abdominal pain patient with Systemic Lupus Erythematosus can develop oral ulcers, mesenteric ischemia (causes abdominal pain), bowel perforation (causes acute abdomen with sudden onset severe abdominal pain, and features of septicaemia), liver failure( right hypochondrial pain, icterus, loss of weight, loss of appetitie) and pancreatitis ( causing diabetes mellitus and features of food indigestion). In an acute flareup patient can develop nausea, vomiting and diarrhoea[27][28].
recurrent infections, easy fatiguabilty, increased bleeding tendency patients can develop neutropenia, lymphopenia, thrombocytopenia and haemolytic anaemia[29][30].
Past gynaecological history of recurrent miscarriages These patients are at risk of getting recurrent miscarriages. The exact mechanism is unknown. There is an increased frequency of an exacerbations during pregnancy and postpartum [40][41].
Obstetric history of exacerbations during pregnancy/ post partum period and History of exacerbations during pregnancy/ post partum period. History of giving birt to a baby with neonatal lupus syndrome. In here neonate will develop rash, hepatitis and heart block[43][44][45].
history of hormone replacement therapy Parimenopausal women in their child bearing ages are at risk of developing Systemic Lupus Erythematosus. Males with Klinefelter’s syndrome also at risk of developing this condition campare to normal males. Hormone replacement therapy is known to induce flareups[2][33].
Drug history Some drugs like hydralazine, isoniazid, procainamide, penicillamine can induce this condition[34][35].
History of exposure to sun light Ultraviolet light is a known triggering factor[2][36][37].
History of recent Epstein–Barr virus infection Exposure to Epstein–Barr virus also a known predisposing factor[38][39].
Family history of diagnosed SLE or feature suggestive of SLE Systemic Lupus Erythematosus goes as a hereditory disease. Deficiencies of the complement genes C1q, C2 or C4 are at risk of developing Systemic Lupus Erythematosus[31][32].
Past medical history In a diagnosed patient complete past medical history will be useful in further management. About previous episodes, complications, tratments given, medications which patient is currently on[42][43].
References
  1. HOPKINSON N. Epidemiology of systemic lupus erythematosus. Ann Rheum Dis [online] 1992 Dec, 51(12):1292-1294 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC100492
  2. MOK CC, LAU CS. Pathogenesis of systemic lupus erythematosus J Clin Pathol [online] 2003 Jul, 56(7):481-490 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769989
  3. CLINICAL VIGNETTES J Gen Intern Med [online] 2004 Apr, 19(Suppl 1):23-83 [viewed 16 October 2014] Available from: doi:10.1111/j.1525-1497.2004.S1006_1.x
  4. COJOCARU M, COJOCARU IM, SILOSI I, VRABIE CD. Gastrointestinal Manifestations in Systemic Autoimmune Diseases Maedica (Buchar) [online] 2011 Jan, 6(1):45-51 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150032
  5. JAMES JA, ROBERTSON JM. Lupus and Epstein-Barr Curr Opin Rheumatol [online] 2012 Jul, 24(4):383-388 [viewed 16 October 2014] Available from: doi:10.1097/BOR.0b013e3283535801
  6. MAIDHOF W, HILAS O. Lupus: An Overview of the Disease And Management Options P T [online] 2012 Apr, 37(4):240-249 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351863
  7. LEVY DM, KAMPHUIS S. Systemic Lupus Erythematosus in Children and Adolescents Pediatr Clin North Am [online] 2012 Apr, 59(2):345-364 [viewed 16 October 2014] Available from: doi:10.1016/j.pcl.2012.03.007
  8. CACCAVO D, DEL PORTO F, GARZIA P, MITTERHOFER A, GALLUZZO S, RIGON A, VADACCA M, NAVAJAS M, AMOROSO A, AFELTRA A. Raynaud's phenomenon and antiphospholipid antibodies in systemic lupus erythematosus: is there an association? Ann Rheum Dis [online] 2003 Oct, 62(10):1003-1005 [viewed 16 October 2014] Available from: doi:10.1136/ard.62.10.1003
  9. MAXWELL CJ, POTTER E, TOWNSEND J. Severe Raynaud's Phenomenon in a Patient With Antinuclear Antibody-Negative Systemic Lupus Erythematosus J Natl Med Assoc [online] 1988 May, 80(5):594-595 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2625762
  10. GAN L, O’HANLON TP, GORDON AS, RIDER LG, MILLER FW, BURBELO PD. Twins discordant for myositis and systemic lupus erythematosus show markedly enriched autoantibodies in the affected twin supporting environmental influences in pathogenesis BMC Musculoskelet Disord [online] :67 [viewed 16 October 2014] Available from: doi:10.1186/1471-2474-15-67
  11. KOLE AK, GHOSH A. CUTANEOUS MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS IN A TERTIARY REFERRAL CENTER Indian J Dermatol [online] 2009, 54(2):132-136 [viewed 16 October 2014] Available from: doi:10.4103/0019-5154.53189
  12. WYSENBEEK AJ, GUEDJ D, AMIT M, WEINBERGER A. Rash in systemic lupus erythematosus: prevalence and relation to cutaneous and non-cutaneous disease manifestations. Ann Rheum Dis [online] 1992 Jun, 51(6):717-719 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1004732
  13. PATEL RM, MARFATIA YS. LUPUS PANNICULITIS AS AN INITIAL MANIFESTATION OF SYSTEMIC LUPUS ERYTHEMATOSUS Indian J Dermatol [online] 2010, 55(1):99-101 [viewed 16 October 2014] Available from: doi:10.4103/0019-5154.60364
  14. GORDON KA, TOSTI A. Alopecia: evaluation and treatment Clin Cosmet Investig Dermatol [online] :101-106 [viewed 16 October 2014] Available from: doi:10.2147/CCID.S10182
  15. PONTICELLI C, IMBASCIATI E, BRANCACCIO D, TARANTINO A, RIVOLTA E. Acute Renal Failure in Systemic Lupus Erythematosus Br Med J [online] 1974 Sep 21, 3(5933):716-719 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1611813
  16. BAGAVANT H, FU SM. Pathogenesis of kidney disease in systemic lupus erythematosus Curr Opin Rheumatol [online] 2009 Sep, 21(5):489-494 [viewed 16 October 2014] Available from: doi:10.1097/BOR.0b013e32832efff1
  17. DE JONGSTE JC, NEIJENS HJ, DUIVERMAN EJ, BOGAARD JM, KERREBIJN KF. Respiratory tract disease in systemic lupus erythematosus. Arch Dis Child [online] 1986 May, 61(5):478-483 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1777806
  18. KEANE M, LYNCH J. Pleuropulmonary manifestations of systemic lupus erythematosus Thorax [online] 2000 Feb, 55(2):159-166 [viewed 16 October 2014] Available from: doi:10.1136/thorax.55.2.159
  19. ZELLER CB, APPENZELLER S. Cardiovascular Disease in Systemic Lupus Erythematosus: The Role of Traditional and Lupus Related Risk Factors Curr Cardiol Rev [online] 2008 May, 4(2):116-122 [viewed 16 October 2014] Available from: doi:10.2174/157340308784245775
  20. ELKAYAM U, WEISS S, LANIADO S. Pericardial effusion and mitral valve involvement in systemic lupus erythematosus. Echocardiographic study. Ann Rheum Dis [online] 1977 Aug, 36(4):349-353 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1006696
  21. TAKEUCHI T, AMANO K, SEKINE H, KOIDE J, ABE T. Upregulated expression and function of integrin adhesive receptors in systemic lupus erythematosus patients with vasculitis. J Clin Invest [online] 1993 Dec, 92(6):3008-3016 [viewed 16 October 2014] Available from: doi:10.1172/JCI116924
  22. D'CRUZ DP, KESER G, DIRESKENELI H, KHAMASHTA MA, HUGHES GR. Anti-endothelial cell antibodies in systemic vasculitis and systemic lupus erythematosus (SLE): effects of heat inactivation on binding and specificity Clin Exp Immunol [online] 1999 Mar, 115(3):567-570 [viewed 16 October 2014] Available from: doi:10.1046/j.1365-2249.1999.00845.x
  23. BRESNIHAN B, OLIVER M, GRIGOR R, HUGHES GR. Brain reactivity of lymphocytotoxic antibodies in systemic lupus erythematosus with and without cerebral involvement. Clin Exp Immunol [online] 1977 Dec, 30(3):333-337 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1541136
  24. PATERSON A, TIMPERLEY W, SLATER D. Coagulation abnormalities in fatal cerebral lupus erythematosus. J R Soc Med [online] 1981 Jan, 74(1):53-55 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1438326
  25. ECKSTEIN MB, SPALTON DJ, HOLDER G. Visual loss from central serous retinopathy in systemic lupus erythematosus. Br J Ophthalmol [online] 1993 Sep, 77(9):607-609 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC513966
  26. THEODORIDOU A, SETTAS L. Demyelination in rheumatic diseases J Neurol Neurosurg Psychiatry [online] 2006 Mar, 77(3):290-295 [viewed 16 October 2014] Available from: doi:10.1136/jnnp.2005.075861
  27. TIAN XP, ZHANG X. Gastrointestinal involvement in systemic lupus erythematosus: Insight into pathogenesis, diagnosis and treatment World J Gastroenterol [online] 2010 Jun 28, 16(24):2971-2977 [viewed 16 October 2014] Available from: doi:10.3748/wjg.v16.i24.2971
  28. JIA Y, ORTIZ A, MCCALLUM R, SALAMEH H, SERRATO P. Acute Pancreatitis as the Initial Presentation of Systematic Lupus Erythematosus Case Rep Gastrointest Med [online] 2014:571493 [viewed 16 October 2014] Available from: doi:10.1155/2014/571493
  29. BASHAL F. Hematological Disorders in Patients with Systemic Lupus Erythematosus Open Rheumatol J [online] :87-95 [viewed 16 October 2014] Available from: doi:10.2174/1874312901307010087
  30. VOULGARELIS M, KOKORI S, IOANNIDIS J, TZIOUFAS A, KYRIAKI D, MOUTSOPOULOS H. Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin Ann Rheum Dis [online] 2000 Mar, 59(3):217-222 [viewed 16 October 2014] Available from: doi:10.1136/ard.59.3.217
  31. EROGLU G, KOHLER P. Familial systemic lupus erythematosus: the role of genetic and environmental factors Ann Rheum Dis [online] 2002 Jan, 61(1):29-31 [viewed 16 October 2014] Available from: doi:10.1136/ard.61.1.29
  32. RAMOS PS, BROWN EE, KIMBERLY RP, LANGEFELD CD. Genetic Factors Predisposing to Systemic Lupus Erythematosus and Lupus Nephritis Semin Nephrol [online] 2010 Mar, 30(2):164-176 [viewed 16 October 2014] Available from: doi:10.1016/j.semnephrol.2010.01.007
  33. ADAMS WALDORF KM, NELSON JL. AUTOIMMUNE DISEASE DURING PREGNANCY AND THE MICROCHIMERISM LEGACY OF PREGNANCY Immunol Invest [online] 2008, 37(5):631-644 [viewed 16 October 2014] Available from: doi:10.1080/08820130802205886
  34. GORDON M, PORTER D, CAPELL H. Does sulphasalazine cause drug induced systemic lupus erythematosus? No effect evident in a prospective randomised trial of 200 rheumatoid patients treated with sulphasalazine or auranofin over five years Ann Rheum Dis [online] 1999 May, 58(5):288-290 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1752876
  35. FRITZLER MJ, TAN EM. Antibodies to Histones in Drug-Induced and Idiopathic Lupus Erythematosus J Clin Invest [online] 1978 Sep, 62(3):560-567 [viewed 16 October 2014] Available from: doi:10.1172/JCI109161
  36. KUECHLE MK, ELKON KB. Shining light on lupus and UV Arthritis Res Ther [online] 2007, 9(1):101 [viewed 16 October 2014] Available from: doi:10.1186/ar2100
  37. KLEIN RS, SAYRE RM, DOWDY JC, WERTH VP. The risk of ultraviolet radiation exposure from indoor lamps in lupus erythematosus Autoimmun Rev [online] 2009 Feb, 8(4):320-324 [viewed 16 October 2014] Available from: doi:10.1016/j.autrev.2008.10.003
  38. DRABORG AH, DUUS K, HOUEN G. Epstein-Barr Virus in Systemic Autoimmune Diseases Clin Dev Immunol [online] 2013:535738 [viewed 16 October 2014] Available from: doi:10.1155/2013/535738
  39. JAMES JA, ROBERTSON JM. Lupus and Epstein-Barr Curr Opin Rheumatol [online] 2012 Jul, 24(4):383-388 [viewed 16 October 2014] Available from: doi:10.1097/BOR.0b013e3283535801
  40. FORD HB, SCHUST DJ. Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy Rev Obstet Gynecol [online] 2009, 2(2):76-83 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709325
  41. JONES HW, IRELAND R, SENALDI G, WANG F, KHAMASHTA M, BELLINGHAM AJ, VEERAPAN K, HUGHES GR, VERGANI D. Anticardiolipin antibodies in patients from Malaysia with systemic lupus erythematosus. Ann Rheum Dis [online] 1991 Mar, 50(3):173-175 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1004368
  42. SWAAK AJ, NOSSENT JC, BRONSVELD W, VAN ROOYEN A, NIEUWENHUYS EJ, THEUNS L, SMEENK RJ. Systemic lupus erythematosus. II. Observations on the occurrence of exacerbations in the disease course: Dutch experience with 110 patients studied prospectively. Ann Rheum Dis [online] 1989 Jun, 48(6):455-460 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1003787
  43. VYAS V, SHUKLA D, PATIL S, MOHITE S. Caesarean section in a case of systemic lupus erythematosus Indian J Anaesth [online] 2014, 58(2):193-195 [viewed 17 October 2014] Available from: doi:10.4103/0019-5049.130827
  44. MOK C, WONG R. Pregnancy in systemic lupus erythematosus Postgrad Med J [online] 2001 Mar, 77(905):157-165 [viewed 17 October 2014] Available from: doi:10.1136/pmj.77.905.157
  45. BARBER KA, JACKSON R. Neonatal lupus erythematosus: five new cases with HLA typing. Can Med Assoc J [online] 1983 Jul 15, 129(2):139-141 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1875279

Examination

Fact Explanation
General examination- febrile, ill looking patient with mild lumphadenopathy and evidence of loss of weight. These symptoms are common during exacerbations due to increased metabolic activity[1][2].
Joint examination characteristically joints are normal despite of pain. Mildly swollen, tender small joints can be identified. These symptoms are usually symmetrical. Rarely joint deformities can be seen due to bony erosions (Jaccoud's arthropathy) and contractions of the joint capsule and tendon following long term inflammatory process. Major joints also can involved[3][4][5].
capillary nail-fold loops examination and observation of Raynaud’s phenomenon This can be done with an ophthalmoscope. It is helpful in distinguishing primary from secondary Raynaud's (loss of the normal loop pattern and capillary 'fallout' with haemorrhage and dots indicate underlying disease). Raynaud’s phenomenon can be observed while patient handling the cool water[6][7].
Muscle examination If the patient is having myositis there will be tenderness on examination[5][8].
examination of the skin On examination there will be various types of rashes. eg: eruthematous rash on the cheeks aross the nasal bridge (butterfly rash). Purpura and urticarial rash over the tip of the fingers and nail folds. Skin changes like Livedo reticularis and periungual erythema. Erythematous rash in face with well defined margins. With time these plques may lead to scarring and pigmentations (Discoid rash). In Subacute cutaneous lupus erythematosus, there will be a migratory, non-scarring, papulosquamous/ annular rash.[9][10]
scalp examination This will reveals alopacia. It can be either scarring or non scarring alopacia[11][12].
look for features of renal impairment and examine urine in presence of haematuria/ proteinuria. Generalized body swelling, pallor, haematuria will suggest the renal involvement[13][14].
Respiratory system examination This will reveals the signs of bilateral pleural effusion( reduced lung expansion, stony dullness on percussion), signs of fibrosis (reduced air entry, presence of brochial breathing, dullness on percussion, increased vocal resonance)[15][16].
Central nervous System examination On examination there will be seizures, cerebral ataxia, features of meningits (headache, photophobia, neck stiffness), cranial nerve palsy, and evidence of polyneuropathy ( muscle weakness, altered sensation, autonomic symptoms)[17][18].
Mental State Examination This will reveals the presence of visual hallucinations, organic psychosis[19].
Examination of the eye General examination of the eye will reveals orbital infections like episcleritis, conjunctivitis and dry mucous membranes (in presence of Sjögren’s syndrome). Visual acuity, colour vision and visual field will be affected in presence of optic neuritis. Fundoscopic examination will reveals retinal infarctions with hard exudates and retinal haemorrhages[20][21].
abdominal examination General examination will reveals oral ulcers, icterus In abdominal examination, mesenteric ischemia will reveals abdominal tenderness, gueding, rigidity will present in peritonitis, hypotension, tachicardia, tachypnoea will present in septicaemia, In liver failure there will be ankle oedema, ascitis[22][23].
Cardiovascular examination In pericarditis with pericardial effusion will associated with pericardial rub. in myocarditis patient will hve arrhythmias( irregular pulse, tacycardia), valve lesions with cardiomyopathy will have murmurs[24][25].
evidence of neutropenia, lymphopenia, thrombocytopenia and haemolytic anaemia evidence of recurrent infection, easy bruising, pallor will present[26][27].
Neonatal examination of a baby born to a mother with Systemic Lupus Erythematosus In here neonate will develop a skin rash, icterus following hepatitis and arrhythmias, syncopial attacks following heart block[28].
References
  1. CLINICAL VIGNETTES J Gen Intern Med [online] 2004 Apr, 19(Suppl 1):23-83 [viewed 16 October 2014] Available from: doi:10.1111/j.1525-1497.2004.S1006_1.x
  2. COJOCARU M, COJOCARU IM, SILOSI I, VRABIE CD. Gastrointestinal Manifestations in Systemic Autoimmune Diseases Maedica (Buchar) [online] 2011 Jan, 6(1):45-51 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150032
  3. LEVY DM, KAMPHUIS S. Systemic Lupus Erythematosus in Children and Adolescents Pediatr Clin North Am [online] 2012 Apr, 59(2):345-364 [viewed 16 October 2014] Available from: doi:10.1016/j.pcl.2012.03.007
  4. COJOCARU M, COJOCARU IM, SILOSI I, VRABIE CD. Manifestations of Systemic Lupus Erythematosus Maedica (Buchar) [online] 2011 Oct, 6(4):330-336 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3391953
  5. MAIDHOF W, HILAS O. Lupus: An Overview of the Disease And Management Options P T [online] 2012 Apr, 37(4):240-249 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351863
  6. MAXWELL CJ, POTTER E, TOWNSEND J. Severe Raynaud's Phenomenon in a Patient With Antinuclear Antibody-Negative Systemic Lupus Erythematosus J Natl Med Assoc [online] 1988 May, 80(5):594-595 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2625762
  7. CACCAVO D, DEL PORTO F, GARZIA P, MITTERHOFER A, GALLUZZO S, RIGON A, VADACCA M, NAVAJAS M, AMOROSO A, AFELTRA A. Raynaud's phenomenon and antiphospholipid antibodies in systemic lupus erythematosus: is there an association? Ann Rheum Dis [online] 2003 Oct, 62(10):1003-1005 [viewed 16 October 2014] Available from: doi:10.1136/ard.62.10.1003
  8. GAN L, O’HANLON TP, GORDON AS, RIDER LG, MILLER FW, BURBELO PD. Twins discordant for myositis and systemic lupus erythematosus show markedly enriched autoantibodies in the affected twin supporting environmental influences in pathogenesis BMC Musculoskelet Disord [online] :67 [viewed 16 October 2014] Available from: doi:10.1186/1471-2474-15-67
  9. KOLE AK, GHOSH A. CUTANEOUS MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS IN A TERTIARY REFERRAL CENTER Indian J Dermatol [online] 2009, 54(2):132-136 [viewed 16 October 2014] Available from: doi:10.4103/0019-5154.53189
  10. WYSENBEEK AJ, GUEDJ D, AMIT M, WEINBERGER A. Rash in systemic lupus erythematosus: prevalence and relation to cutaneous and non-cutaneous disease manifestations. Ann Rheum Dis [online] 1992 Jun, 51(6):717-719 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1004732
  11. PATEL RM, MARFATIA YS. LUPUS PANNICULITIS AS AN INITIAL MANIFESTATION OF SYSTEMIC LUPUS ERYTHEMATOSUS Indian J Dermatol [online] 2010, 55(1):99-101 [viewed 16 October 2014] Available from: doi:10.4103/0019-5154.60364
  12. GORDON KA, TOSTI A. Alopecia: evaluation and treatment Clin Cosmet Investig Dermatol [online] :101-106 [viewed 16 October 2014] Available from: doi:10.2147/CCID.S10182
  13. BAGAVANT H, FU SM. Pathogenesis of kidney disease in systemic lupus erythematosus Curr Opin Rheumatol [online] 2009 Sep, 21(5):489-494 [viewed 16 October 2014] Available from: doi:10.1097/BOR.0b013e32832efff1
  14. PONTICELLI C, IMBASCIATI E, BRANCACCIO D, TARANTINO A, RIVOLTA E. Acute Renal Failure in Systemic Lupus Erythematosus Br Med J [online] 1974 Sep 21, 3(5933):716-719 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1611813
  15. KEANE M, LYNCH J. Pleuropulmonary manifestations of systemic lupus erythematosus Thorax [online] 2000 Feb, 55(2):159-166 [viewed 16 October 2014] Available from: doi:10.1136/thorax.55.2.159
  16. DE JONGSTE JC, NEIJENS HJ, DUIVERMAN EJ, BOGAARD JM, KERREBIJN KF. Respiratory tract disease in systemic lupus erythematosus. Arch Dis Child [online] 1986 May, 61(5):478-483 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1777806
  17. PATERSON A, TIMPERLEY W, SLATER D. Coagulation abnormalities in fatal cerebral lupus erythematosus. J R Soc Med [online] 1981 Jan, 74(1):53-55 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1438326
  18. BRESNIHAN B, OLIVER M, GRIGOR R, HUGHES GR. Brain reactivity of lymphocytotoxic antibodies in systemic lupus erythematosus with and without cerebral involvement. Clin Exp Immunol [online] 1977 Dec, 30(3):333-337 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1541136
  19. NAYAK RB, BHOGALE GS, PATIL NM, CHATE SS. Psychosis in Patients with Systemic Lupus Erythematosus Indian J Psychol Med [online] 2012, 34(1):90-93 [viewed 16 October 2014] Available from: doi:10.4103/0253-7176.96170
  20. THEODORIDOU A, SETTAS L. Demyelination in rheumatic diseases J Neurol Neurosurg Psychiatry [online] 2006 Mar, 77(3):290-295 [viewed 16 October 2014] Available from: doi:10.1136/jnnp.2005.075861
  21. ECKSTEIN MB, SPALTON DJ, HOLDER G. Visual loss from central serous retinopathy in systemic lupus erythematosus. Br J Ophthalmol [online] 1993 Sep, 77(9):607-609 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC513966
  22. JIA Y, ORTIZ A, MCCALLUM R, SALAMEH H, SERRATO P. Acute Pancreatitis as the Initial Presentation of Systematic Lupus Erythematosus Case Rep Gastrointest Med [online] 2014:571493 [viewed 16 October 2014] Available from: doi:10.1155/2014/571493
  23. TIAN XP, ZHANG X. Gastrointestinal involvement in systemic lupus erythematosus: Insight into pathogenesis, diagnosis and treatment World J Gastroenterol [online] 2010 Jun 28, 16(24):2971-2977 [viewed 16 October 2014] Available from: doi:10.3748/wjg.v16.i24.2971
  24. ELKAYAM U, WEISS S, LANIADO S. Pericardial effusion and mitral valve involvement in systemic lupus erythematosus. Echocardiographic study. Ann Rheum Dis [online] 1977 Aug, 36(4):349-353 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1006696
  25. ZELLER CB, APPENZELLER S. Cardiovascular Disease in Systemic Lupus Erythematosus: The Role of Traditional and Lupus Related Risk Factors Curr Cardiol Rev [online] 2008 May, 4(2):116-122 [viewed 16 October 2014] Available from: doi:10.2174/157340308784245775
  26. VOULGARELIS M, KOKORI S, IOANNIDIS J, TZIOUFAS A, KYRIAKI D, MOUTSOPOULOS H. Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin Ann Rheum Dis [online] 2000 Mar, 59(3):217-222 [viewed 16 October 2014] Available from: doi:10.1136/ard.59.3.217
  27. BASHAL F. Hematological Disorders in Patients with Systemic Lupus Erythematosus Open Rheumatol J [online] :87-95 [viewed 16 October 2014] Available from: doi:10.2174/1874312901307010087
  28. BARBER KA, JACKSON R. Neonatal lupus erythematosus: five new cases with HLA typing. Can Med Assoc J [online] 1983 Jul 15, 129(2):139-141 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1875279

Differential Diagnoses

Fact Explanation
Antiphospholipid antibody Syndrome this is another connective tissue disorder with prominent vascular thromboses There will be associated hypertension, pulmonary hypertension, epilepsy, thrombocytopenia, leg ulcers and valvular problems. This condition either can be present as a primary disease or secondary to another connective tissue disorder. There are diagnostic criteria which help to differentiate from SLE[3][4].
Systemic sclerosis Systemic sclerosis is another connective tissue disorder affecting multi systems. there will be prominent sclerodactyly associated with Raynaud's phenomenon. Also there will be more digital ischaemia campare to Systemic Lupus Erythematosus. The condition is common among females in there fourth and fifth decades. The clinical features which are devided into majoe groups like calcinosis, Raynaud's, oesophageal involvement, sclerodactyly, telangiectasia[1][2].
Mixed connective tissue disorder In this condition overlapping the symptoms of systemic lupus erythematosus, systemic sclerosis and myositis can be identified. So the will have synovitis, oedema of the hands, raynand's penomenon and muscle pain pr weakness[5][6].
Rheumatoid arthritis This is an inflammatory arthritis, commonly occur in women. There will be symmetrical, deforming, small and large joint polyarthritis. Also rheumatoid arthritis can be associated with extra articular manifestations. eg: fever, fatigue, weight loss, anaemia, thrombocytopenia, muscle waisting, episcleritis, scleritis, ulcers, digital arteritis, pericarditis, myocarditis, endocarditis, pleural effusion, fibrosing alveolitis, peripheral neuropathy. Criteria for diagnosis of rheumatoid arthritis will help to differentiate the condition from systemic lupus erythematosus[7][8].
Interstitial lung disease This condition is associated with diffuse thickening of the alveolar wall with inflammatory cells and exudate, some times with granulomas, alveolar haemorrhages and fibrosis. This can occur as an isolated condition. In here absence other features of SLE will help to diagnose the disease[9][10].
Glomerulonephritis Glomerulonephritis in an immunological mediated disease causing renal failure. Similer to there are many other causes which can induce this condition. eg: infections, inflammatory/ immune conditions ( sarcoidosis), cryoglobulinaemia, toxins, drugs, So there conditions need to be excluded in diagnosing Glomerulonephritis due to SLE[11][12].
Septic Meningitis Septic meningitis can caused by virus, bacteria or fungi. SLE can induce aseptic meningitis following auto immune inflammatory process. Both will give typical features of meningitis like fever, headache, photophobia and neck stiffness. So CSF studies will helpful in differentiating aseptic meningitis from septic one[13][14].
Other causes of haemolytic anaemia Haemolytic anaemia can occur following hereditary causes like hereditary spherocytosis, G6PD deficiency, genetic abnormalities of the haermoglobin and due to acquired causes like autoimmune disease, drugs, infections, chemicals and secondary to renal/ liver diseases. So there causes need to be excluded inthe presence of haemolytic anaemia[15][16].
References
  1. KRAAIJ MD, VAN LAAR JM. The role of B cells in systemic sclerosis Biologics [online] 2008 Sep, 2(3):389-395 [viewed 18 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721390
  2. MEDSGER TA JR. Treatment of systemic sclerosis. Ann Rheum Dis [online] 1991 Nov, 50(Suppl 4):877-886 [viewed 18 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1033324
  3. DI PRIMA FA, VALENTI O, HYSENI E, GIORGIO E, FARACI M, RENDA E, DE DOMENICO R, MONTE S. Antiphospholipid Syndrome during pregnancy: the state of the art J Prenat Med [online] 2011, 5(2):41-53 [viewed 18 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279165
  4. CERVERA R, ASHERSON R, ACEVEDO M, GOMEZ-PUERTA J, ESPINOSA G, DE LA RED G, GIL V, RAMOS-CASALS M, GARCIA-CARRASCO M, INGELMO M, FONT J. Antiphospholipid syndrome associated with infections: clinical and microbiological characteristics of 100 patients Ann Rheum Dis [online] 2004 Oct, 63(10):1312-1317 [viewed 18 October 2014] Available from: doi:10.1136/ard.2003.014175
  5. SEN S, SINHAMAHAPATRA P, CHOUDHURY S, GANGOPADHYAY A, BALA S, SIRCAR G, CHATTERJEE G, GHOSH A. Cutaneous Manifestations of Mixed Connective Tissue Disease: Study from a Tertiary Care Hospital in Eastern India Indian J Dermatol [online] 2014, 59(1):35-40 [viewed 18 October 2014] Available from: doi:10.4103/0019-5154.123491
  6. LATUśKIEWICZ-POTEMSKA J, ZYGMUNT A, BIERNACKA-ZIELIńSKA M, STAńCZYK J, SMOLEWSKA E. Mixed connective tissue disease presenting with progressive scleroderma symptoms in a 10-year-old girl Postepy Dermatol Alergol [online] 2013 Oct, 30(5):329-336 [viewed 18 October 2014] Available from: doi:10.5114/pdia.2013.38365
  7. ZONANA-NACACH A, ALARCóN GS, DANIEL WW. Rheumatoid arthritis preceding the onset of polyarticular tophaceous gout. Ann Rheum Dis [online] 1996 Jul, 55(7):489-490 [viewed 18 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1010218
  8. DAVIS JM III, MATTESON EL. My Treatment Approach to Rheumatoid Arthritis Mayo Clin Proc [online] 2012 Jul, 87(7):659-673 [viewed 18 October 2014] Available from: doi:10.1016/j.mayocp.2012.03.011
  9. SMYTH RL, CARTY H, THOMAS H, VAN VELZEN D, HEAF D. Diagnosis of interstitial lung disease by a percutaneous lung biopsy sample. Arch Dis Child [online] 1994 Feb, 70(2):143-144 [viewed 18 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1029721
  10. BOURKE SJ. Interstitial lung disease: progress and problems Postgrad Med J [online] 2006 Aug, 82(970):494-499 [viewed 18 October 2014] Available from: doi:10.1136/pgmj.2006.046417
  11. MCCOY RC, TISHER CC. Glomerulonephritis Associated with Sarcoidosis Am J Pathol [online] 1972 Aug, 68(2):339-358 [viewed 18 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2032674
  12. RAMMELKAMP CH JR, WEAVER RS. ACUTE GLOMERULONEPHRITIS. THE SIGNIFICANCE OF THE VARIATIONS IN THE INCIDENCE OF THE DISEASE J Clin Invest [online] 1953 Apr, 32(4):345-358 [viewed 18 October 2014] Available from: doi:10.1172/JCI102745
  13. HOFFMAN O, WEBER RJ. Pathophysiology and Treatment of Bacterial Meningitis Ther Adv Neurol Disord [online] 2009 Nov, 2(6):1-7 [viewed 18 October 2014] Available from: doi:10.1177/1756285609337975
  14. BROUWER MC, TUNKEL AR, VAN DE BEEK D. Epidemiology, Diagnosis, and Antimicrobial Treatment of Acute Bacterial Meningitis Clin Microbiol Rev [online] 2010 Jul, 23(3):467-492 [viewed 18 October 2014] Available from: doi:10.1128/CMR.00070-09
  15. BRODY JI, FINCH SC. SERUM FACTORS OF ACQUIRED HEMOLYTIC ANEMIA IN LEUKEMIA AND LYMPHOMA J Clin Invest [online] 1961 Feb, 40(2):181-187 [viewed 18 October 2014] Available from: doi:10.1172/JCI104243
  16. SOKOL RJ, BOOKER DJ, STAMPS R. The pathology of autoimmune haemolytic anaemia. J Clin Pathol [online] 1992 Dec, 45(12):1047-1052 [viewed 18 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC494994

Investigations - for Diagnosis

Fact Explanation
full blood count patients can develop neutropenia, lymphopenia, thrombocytopenia and anaemia (Anaemia of chronic disease or autoimmune haemolytic anaemia)[1][2]
ESR, CRP In a controlled disease ESR will be high but CRP will be normal. But if there is any active inflammatory condition is present, CRP will be high[3][4].
Autoantibodies like ANA, anti-dsDNA, anti-Ro, anti-Sm and anti-La There are several antibodies present in Systemic Lupus Erythematosus. ANA are positive in more than 95% of patients[5][6].
Serum complement C3 and C4 levels These are normal during the remission but levels are low during flareups[7][8].
Renal function tests like UFR, serum creatinine, blood ures These tests help in diagnosing the renal involvement[15][16].
Liver function tests like AST, ALT, serum billirubin, serum albumin level and Ultrasound scan of the abdomen Liver function tests helpful in diagnosing the liver involvement and Ultrasound scan of the abdomen will help to assess the presence of ascitis [17][18].
ECG, Echocardiogram These will be helpful in diagnosing the cardiovascular complications like pericardial effusions, arrhythmias, and valvular abnormalities[13][14].
Chest X ray As Systemic Lupus Erythematosus can cause pulmonary involvement, Chest X ray is useful[19][20].
CT/ MRI scan of brain These tests will be useful in assessing cerebral complications. Brain arophy, brain infarction following vasculitis can be identified[11][12].
pleural aspirates for cytology, culture and ABST In the presence of pleural effusion these tests useful in identifyint the exudate anfd excluding pulmonary infections[19][20].
Histological and immunofluorescent study of biopsies from the kidney and the skin In these studies deposition of IgG and complement will be identified. This will be useful in classifying the lupus nephritis as well[9][10].
CSF studies like CSF full report, culture and ABST These will be helpful in excluding the septic meningitis in patients with clinical symptoms and signd suggestive of meningitis[11][12].
References
  1. VOULGARELIS M, KOKORI S, IOANNIDIS J, TZIOUFAS A, KYRIAKI D, MOUTSOPOULOS H. Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin Ann Rheum Dis [online] 2000 Mar, 59(3):217-222 [viewed 16 October 2014] Available from: doi:10.1136/ard.59.3.217
  2. BASHAL F. Hematological Disorders in Patients with Systemic Lupus Erythematosus Open Rheumatol J [online] :87-95 [viewed 16 October 2014] Available from: doi:10.2174/1874312901307010087
  3. BERTOUCH JV, ROBERTS-THOMPSON PJ, FENG PH, BRADLEY J. C-reactive protein and serological indices of disease activity in systemic lupus erythematosus. Ann Rheum Dis [online] 1983 Dec, 42(6):655-658 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1001323
  4. BOEHME MW, RAETH U, GALLE PR, STREMMEL W, SCHERBAUM WA. Serum thrombomodulin--a reliable marker of disease activity in systemic lupus erythematosus (SLE): advantage over established serological parameters to indicate disease activity Clin Exp Immunol [online] 2000 Jan, 119(1):189-195 [viewed 16 October 2014] Available from: doi:10.1046/j.1365-2249.2000.01107.x
  5. FISHBEIN E, ALARCON-SEGOVIA D, VEGA JM. Antibodies to histones in systemic lupus erythematosus. Clin Exp Immunol [online] 1979 Apr, 36(1):145-150 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1537691
  6. LANDRY M, SAMS WM JR. Systemic Lupus Erythematosus. STUDIES OF THE ANTIBODIES BOUND TO SKIN J Clin Invest [online] 1973 Aug, 52(8):1871-1880 [viewed 16 October 2014] Available from: doi:10.1172/JCI107370
  7. CHARLESWORTH JA, PEAKE PW, GOLDING J, MACKIE JD, PUSSELL BA, TIMMERMANS V, WAKEFIELD D. Hypercatabolism of C3 and C4 in active and inactive systemic lupus erythematosus. Ann Rheum Dis [online] 1989 Feb, 48(2):153-159 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1003704
  8. TSUKAMOTO H, UEDA A, NAGASAWA K, TADA Y, NIHO Y. Increased production of the third component of complement (C3) by monocytes from patients with systemic lupus erythematosus. Clin Exp Immunol [online] 1990 Nov, 82(2):257-261 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1535108
  9. FONT J, CERVERA R, INGELMO M, TORRAS A, DARNELL A, REVERT L. Systemic lupus erythematosus without clinical renal abnormalities. Ann Rheum Dis [online] 1986 Mar, 45(3):260-261 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1001862
  10. PARONETTO F, KOFFLER D. Immunofluorescent localization of immunoglobulins, complement, and fibrinogen in human diseases. I. Systemic lupus erythematosus. J Clin Invest [online] 1965 Oct, 44(10):1657-1664 [viewed 16 October 2014] Available from: doi:10.1172/JCI105272
  11. MUSCAL E, BREY RL. Neurological Manifestations of Systemic Lupus Erythematosus in Children and Adults Neurol Clin [online] 2010 Feb, 28(1):61-73 [viewed 16 October 2014] Available from: doi:10.1016/j.ncl.2009.09.004
  12. BERLIT P. Diagnosis and treatment of cerebral vasculitis Ther Adv Neurol Disord [online] 2010 Jan, 3(1):29-42 [viewed 16 October 2014] Available from: doi:10.1177/1756285609347123
  13. ELKAYAM U, WEISS S, LANIADO S. Pericardial effusion and mitral valve involvement in systemic lupus erythematosus. Echocardiographic study. Ann Rheum Dis [online] 1977 Aug, 36(4):349-353 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1006696
  14. ZELLER CB, APPENZELLER S. Cardiovascular Disease in Systemic Lupus Erythematosus: The Role of Traditional and Lupus Related Risk Factors Curr Cardiol Rev [online] 2008 May, 4(2):116-122 [viewed 16 October 2014] Available from: doi:10.2174/157340308784245775
  15. BAGAVANT H, FU SM. Pathogenesis of kidney disease in systemic lupus erythematosus Curr Opin Rheumatol [online] 2009 Sep, 21(5):489-494 [viewed 16 October 2014] Available from: doi:10.1097/BOR.0b013e32832efff1
  16. PONTICELLI C, IMBASCIATI E, BRANCACCIO D, TARANTINO A, RIVOLTA E. Acute Renal Failure in Systemic Lupus Erythematosus Br Med J [online] 1974 Sep 21, 3(5933):716-719 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1611813
  17. JIA Y, ORTIZ A, MCCALLUM R, SALAMEH H, SERRATO P. Acute Pancreatitis as the Initial Presentation of Systematic Lupus Erythematosus Case Rep Gastrointest Med [online] 2014:571493 [viewed 16 October 2014] Available from: doi:10.1155/2014/571493
  18. TIAN XP, ZHANG X. Gastrointestinal involvement in systemic lupus erythematosus: Insight into pathogenesis, diagnosis and treatment World J Gastroenterol [online] 2010 Jun 28, 16(24):2971-2977 [viewed 16 October 2014] Available from: doi:10.3748/wjg.v16.i24.2971
  19. KEANE M, LYNCH J. Pleuropulmonary manifestations of systemic lupus erythematosus Thorax [online] 2000 Feb, 55(2):159-166 [viewed 16 October 2014] Available from: doi:10.1136/thorax.55.2.159
  20. DE JONGSTE JC, NEIJENS HJ, DUIVERMAN EJ, BOGAARD JM, KERREBIJN KF. Respiratory tract disease in systemic lupus erythematosus. Arch Dis Child [online] 1986 May, 61(5):478-483 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1777806

Investigations - Fitness for Management

Fact Explanation
FBC This will be useful in looking for platelet count, haemoglobin level and WBC count when preparing the patient for invasive procedures[1][2].
Clotting profile test with PT/INR, APTT Thesetest also useful to assess theclooting atatus of the patient[7][8].
Renal function tests like UFR, serum creatinine, blood urea, Assessment of the renal function of the patient is useful during imaging and invasive procedures[3][4].
Liver function tests like AST, ALT, serum billirubin, serum albumin level and Ultrasound scan of the abdomen Liver function tests helpful in managemet to diagnosing the liver involvement [9][10].
ECG, Echocardiogram These will be helpful in diagnosing the cardiovascular complications during themanagement[5][6].
Chest X ray Chest X ray is also useful in assessing the fitness of the patient[11][12].
References
  1. VOULGARELIS M, KOKORI S, IOANNIDIS J, TZIOUFAS A, KYRIAKI D, MOUTSOPOULOS H. Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin Ann Rheum Dis [online] 2000 Mar, 59(3):217-222 [viewed 16 October 2014] Available from: doi:10.1136/ard.59.3.217
  2. BASHAL F. Hematological Disorders in Patients with Systemic Lupus Erythematosus Open Rheumatol J [online] :87-95 [viewed 16 October 2014] Available from: doi:10.2174/1874312901307010087
  3. PONTICELLI C, IMBASCIATI E, BRANCACCIO D, TARANTINO A, RIVOLTA E. Acute Renal Failure in Systemic Lupus Erythematosus Br Med J [online] 1974 Sep 21, 3(5933):716-719 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1611813
  4. BAGAVANT H, FU SM. Pathogenesis of kidney disease in systemic lupus erythematosus Curr Opin Rheumatol [online] 2009 Sep, 21(5):489-494 [viewed 16 October 2014] Available from: doi:10.1097/BOR.0b013e32832efff1
  5. ZELLER CB, APPENZELLER S. Cardiovascular Disease in Systemic Lupus Erythematosus: The Role of Traditional and Lupus Related Risk Factors Curr Cardiol Rev [online] 2008 May, 4(2):116-122 [viewed 16 October 2014] Available from: doi:10.2174/157340308784245775
  6. ELKAYAM U, WEISS S, LANIADO S. Pericardial effusion and mitral valve involvement in systemic lupus erythematosus. Echocardiographic study. Ann Rheum Dis [online] 1977 Aug, 36(4):349-353 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1006696
  7. BONTEMPO FA, LEWIS JH, VAN THIEL DH, SPERO JA, RAGNI MV, BUTLER P, ISRAEL L, STARZL TE. THE RELATION OF PREOPERATIVE COAGULATION FINDINGS TO DIAGNOSIS, BLOOD USAGE, AND SURVIVAL IN ADULT LIVER TRANSPLANTATION Transplantation [online] 1985 May, 39(5):532-536 [viewed 20 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988424
  8. BENARROCH-GAMPEL J, SHEFFIELD KM, DUNCAN CB, BROWN KM, HAN Y, TOWNSEND CM JR, RIALL TS. Preoperative Laboratory Testing in Patients Undergoing Elective, Low-Risk Ambulatory Surgery Ann Surg [online] 2012 Sep, 256(3):518-528 [viewed 20 October 2014] Available from: doi:10.1097/SLA.0b013e318265bcdb
  9. TIAN XP, ZHANG X. Gastrointestinal involvement in systemic lupus erythematosus: Insight into pathogenesis, diagnosis and treatment World J Gastroenterol [online] 2010 Jun 28, 16(24):2971-2977 [viewed 16 October 2014] Available from: doi:10.3748/wjg.v16.i24.2971
  10. JIA Y, ORTIZ A, MCCALLUM R, SALAMEH H, SERRATO P. Acute Pancreatitis as the Initial Presentation of Systematic Lupus Erythematosus Case Rep Gastrointest Med [online] 2014:571493 [viewed 16 October 2014] Available from: doi:10.1155/2014/571493
  11. DE JONGSTE JC, NEIJENS HJ, DUIVERMAN EJ, BOGAARD JM, KERREBIJN KF. Respiratory tract disease in systemic lupus erythematosus. Arch Dis Child [online] 1986 May, 61(5):478-483 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1777806
  12. KEANE M, LYNCH J. Pleuropulmonary manifestations of systemic lupus erythematosus Thorax [online] 2000 Feb, 55(2):159-166 [viewed 16 October 2014] Available from: doi:10.1136/thorax.55.2.159

Investigations - Followup

Fact Explanation
FBC, blood picture and reticulocyte count patients can develop neutropenia, lymphopenia, thrombocytopenia and anaemia (Anaemia of chronic disease or autoimmune haemolytic anaemia). blood picture will show normocytic normochromic anaemia with low counts of WBC and platelets. Reticulocyte count will be high[9][10][16]
ESR, CRP In a controlled disease ESR will be high but CRP will be normal. But if there is any active inflammatory condition is present, CRP will be high[7][8].
Serum complement C3 and C4 levels These are normal during the remission but levels are low during flareups[5][6].
Histological and immunofluorescent study of biopsies from the kidney and the skin In these studies deposition of IgG and complement will be identified. This will be useful in classifying the lupus nephritis as well[3][4].
Muscle biopsy There will be necrosis and inflammation on muscle biopsy in the presence of myositis[1][2].
Trans vaginal scan These patient are at risk of having recurrent miscarriages. So TVS will be helpful in assessing the patients condition[11][12].
Antiphospholipid antibodies This will give an idea about the prognosis of the patient as 25-40% of patients with positive Antiphospholipid antibodies will develop Antiphospholipid syndrome in future[13][14].
Neonates investigate for neonatal lupus syndrome, Investigations like, Ultrasound scan of the abdomen and liver function tests like AST,ALT, Serum bilirubin to look for any evidence of hepatitis. ECG, Echocardiogram to look for the presence of heart block[15].
References
  1. GAN L, O’HANLON TP, GORDON AS, RIDER LG, MILLER FW, BURBELO PD. Twins discordant for myositis and systemic lupus erythematosus show markedly enriched autoantibodies in the affected twin supporting environmental influences in pathogenesis BMC Musculoskelet Disord [online] :67 [viewed 16 October 2014] Available from: doi:10.1186/1471-2474-15-67
  2. MAIDHOF W, HILAS O. Lupus: An Overview of the Disease And Management Options P T [online] 2012 Apr, 37(4):240-249 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351863
  3. PARONETTO F, KOFFLER D. Immunofluorescent localization of immunoglobulins, complement, and fibrinogen in human diseases. I. Systemic lupus erythematosus. J Clin Invest [online] 1965 Oct, 44(10):1657-1664 [viewed 16 October 2014] Available from: doi:10.1172/JCI105272
  4. FONT J, CERVERA R, INGELMO M, TORRAS A, DARNELL A, REVERT L. Systemic lupus erythematosus without clinical renal abnormalities. Ann Rheum Dis [online] 1986 Mar, 45(3):260-261 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1001862
  5. TSUKAMOTO H, UEDA A, NAGASAWA K, TADA Y, NIHO Y. Increased production of the third component of complement (C3) by monocytes from patients with systemic lupus erythematosus. Clin Exp Immunol [online] 1990 Nov, 82(2):257-261 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1535108
  6. CHARLESWORTH JA, PEAKE PW, GOLDING J, MACKIE JD, PUSSELL BA, TIMMERMANS V, WAKEFIELD D. Hypercatabolism of C3 and C4 in active and inactive systemic lupus erythematosus. Ann Rheum Dis [online] 1989 Feb, 48(2):153-159 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1003704
  7. BOEHME MW, RAETH U, GALLE PR, STREMMEL W, SCHERBAUM WA. Serum thrombomodulin--a reliable marker of disease activity in systemic lupus erythematosus (SLE): advantage over established serological parameters to indicate disease activity Clin Exp Immunol [online] 2000 Jan, 119(1):189-195 [viewed 16 October 2014] Available from: doi:10.1046/j.1365-2249.2000.01107.x
  8. BERTOUCH JV, ROBERTS-THOMPSON PJ, FENG PH, BRADLEY J. C-reactive protein and serological indices of disease activity in systemic lupus erythematosus. Ann Rheum Dis [online] 1983 Dec, 42(6):655-658 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1001323
  9. BASHAL F. Hematological Disorders in Patients with Systemic Lupus Erythematosus Open Rheumatol J [online] :87-95 [viewed 16 October 2014] Available from: doi:10.2174/1874312901307010087
  10. VOULGARELIS M, KOKORI S, IOANNIDIS J, TZIOUFAS A, KYRIAKI D, MOUTSOPOULOS H. Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin Ann Rheum Dis [online] 2000 Mar, 59(3):217-222 [viewed 16 October 2014] Available from: doi:10.1136/ard.59.3.217
  11. JONES HW, IRELAND R, SENALDI G, WANG F, KHAMASHTA M, BELLINGHAM AJ, VEERAPAN K, HUGHES GR, VERGANI D. Anticardiolipin antibodies in patients from Malaysia with systemic lupus erythematosus. Ann Rheum Dis [online] 1991 Mar, 50(3):173-175 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1004368
  12. FORD HB, SCHUST DJ. Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy Rev Obstet Gynecol [online] 2009, 2(2):76-83 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709325
  13. GHIRARDELLO A, DORIA A, RUFFATTI A, RIGOLI AM, VESCO P, CALLIGARO A, GAMBARI PF. Antiphospholipid antibodies (aPL) in systemic lupus erythematosus. Are they specific tools for the diagnosis of aPL syndrome? Ann Rheum Dis [online] 1994 Feb, 53(2):140-142 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1005268
  14. HOPKINSON NP, LIM K, GARDNER-MEDWIN J. Antiphospholipid antibodies (aPL) in systemic lupus erythematosus. Are they specific tools for the diagnosis of aPL syndrome? Ann Rheum Dis [online] 1994 Sep, 53(9):619-620 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1005420
  15. BARBER KA, JACKSON R. Neonatal lupus erythematosus: five new cases with HLA typing. Can Med Assoc J [online] 1983 Jul 15, 129(2):139-141 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1875279
  16. SOKOL RJ, BOOKER DJ, STAMPS R. The pathology of autoimmune haemolytic anaemia. J Clin Pathol [online] 1992 Dec, 45(12):1047-1052 [viewed 18 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC494994

Investigations - Screening/Staging

Fact Explanation
American Rheumatism Association Criteria for Systemic Lupus Erythematosus diagnosis (four or more of these features need to be present serially or simultaneously, on two separate occasions) Malar rash- Fixed erythema, flat or raised, sparing the nasolabial folds Discoid rash- Erythematous raised patches with adherent keratotic scarring and follicular plugging Photosensitivity- Rash as a result of unusual reaction to sunlight Oral ulcers- Oral or nasopharyngeal ulceration, which may be painless Arthritis- Non-erosive, involving two or more peripheral joints Serositis- Pleuritis (convincing history of pleuritic pain or rub, or pleural effusion) or Pericarditis (rub, ECG evidence oreffusion) Renal disorder- Persistent proteinuria > 0.5 g/day or Cellular casts (red cell, granular or tubular) Neurological disorder- Seizures or psychosis, in the absence of offending drugs or metabolic derangement Haematological disorder- Haemolytic anaemia or Leucopenia2 (< 4 ××109/l), or Lymphopenia2 (< 1 ××109/l), or Thrombocytopenia2 (< 100 ××109/l) in the absence of offending drugs Immunological disorder- Anti-DNA antibodies in abnormal titre or Presence of antibody to Sm antigen or Positive antiphospholipid antibodies Antinuclear antibody (ANA) disorder- Abnormal titre of ANA by immunofluorescence [3][4]
Classification of Lupus Nephritis by international Society Of Nephrology and Renal pathology Society Class I – Minimal mesangial lupus nephritis: with immune deposits but normal on light microscopy. Asymptomatic. Class II – Mesangial proliferative lupus nephritis: with mesangial hypercellularity and matrix expansion. Clinically, mild renal disease. Class III – Focal lupus nephritis: (involving < 50% of glomeruli) with subdivisions for active or chronic lesions. Subepithelial deposits seen. Clinically have haematuria and proteinuria. 10–20% of all lupus nephritis. Class IV – Diffuse lupus nephritis: (involving ≥ 50% of glomeruli) classified by the presence of segmental and global lesions as well as active and chronic lesions. Subendothelial deposits are present. Clinically there is progression to the nephrotic syndrome, hypertension and renal insufficiency. Most common and most severe form of lupus nephritis. Class V – Membranous lupus nephritis: affects 10–20% of patients. Can occur in combination with III or IV. Good prognosis. Class VI – Advanced sclerosing lupus nephritis: (≥ 90% globally sclerosed glomeruli without residual activity). This represents the advanced stages of the above, as well as healing. Immunosuppressive therapy is unlikely to help as it is ‘inactive’. Progressive renal failure.[5][6]
Urine for protein and red blood cells As these patients are at risk of developing renal failure all patients are regularly screened and look for presence of protein and red blood cells in the urine. Fro these tests lupus nephritis can be diagnosed in early stages before going into renal impairment[1][2].
Uterine artery doppler study This should be done at 24 weeks of pregnancy associated with systemic lupus erythematosus to screen the foetal growht and well being[7][8].
References
  1. BAGAVANT H, FU SM. Pathogenesis of kidney disease in systemic lupus erythematosus Curr Opin Rheumatol [online] 2009 Sep, 21(5):489-494 [viewed 16 October 2014] Available from: doi:10.1097/BOR.0b013e32832efff1
  2. PONTICELLI C, IMBASCIATI E, BRANCACCIO D, TARANTINO A, RIVOLTA E. Acute Renal Failure in Systemic Lupus Erythematosus Br Med J [online] 1974 Sep 21, 3(5933):716-719 [viewed 16 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1611813
  3. SAMANTA A, FEEHALLY J, ROY S, NICHOL FE, SHELDON PJ, WALLS J. High prevalence of systemic disease and mortality in Asian subjects with systemic lupus erythematosus. Ann Rheum Dis [online] 1991 Jul, 50(7):490-492 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1004464
  4. VELTHUIS PJ, KATER L, VAN DER TWEEL I, DE LA FAILLE HB, VAN VLOTEN WA. Immunofluorescence microscopy of healthy skin from patients with systemic lupus erythematosus: more than just the lupus band. Ann Rheum Dis [online] 1992 Jun, 51(6):720-725 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1004733
  5. MUBARAK M, NASRI H. ISN/RPS 2003 classification of lupus nephritis: time to take a look on the achievements and limitations of the schema J Nephropathol [online] 2014 Jul, 3(3):87-90 [viewed 17 October 2014] Available from: doi:10.12860/jnp.2014.17
  6. ANDERS HJ, WEENING JJ. Kidney disease in lupus is not always 'lupus nephritis' Arthritis Res Ther [online] 2013, 15(2):108 [viewed 17 October 2014] Available from: doi:10.1186/ar4166
  7. ERGIN RN. Pregnancy-associated systemic lupus erythematosus Proc (Bayl Univ Med Cent) [online] 2014 Jul, 27(3):221-222 [viewed 18 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059571
  8. SMYTH A, OLIVEIRA GH, LAHR BD, BAILEY KR, NORBY SM, GAROVIC VD. A Systematic Review and Meta-Analysis of Pregnancy Outcomes in Patients with Systemic Lupus Erythematosus and Lupus Nephritis Clin J Am Soc Nephrol [online] 2010 Nov, 5(11):2060-2068 [viewed 18 October 2014] Available from: doi:10.2215/CJN.00240110

Management - General Measures

Fact Explanation
Health education Patient should be educated regarding the disease, symptoms associated with, possible complications, investigations needed, available treatment options, predisposing factors for exacerbations and prognosis. As this is a life long genetically transmitting disease that fact also need to be address[1][2].
Life style modification Due to the symptoms associated with the disease patient's normal day to day life can be affected. eg: malaise, lethargy, fatiguability will limit the patient to bed. Joint pain and deformities will interfere with fine works. This should be discussed with the patient and physiotherapy, occupational therapy and help from social services can be afforded to improve the quality of life[3][4].
Avoid precipitating factors Patient should be provide informations regarding precipitating factors like excessive exposure to sun light, drugs causing exacerbations and hormone replacement therapy. These factors should be avoided (eg: use high factor sun blocks to minimize UV light exposure) as much as possible and patient should be educated to early identification of exacerbations[5][6].
References
  1. LAWSON EF, YAZDANY J. Healthcare quality in systemic lupus erythematosus: using Donabedian's conceptual framework to understand what we know Int J Clin Rheumtol [online] 2012 Feb, 7(1):95-107 [viewed 17 October 2014] Available from: doi:10.2217/ijr.11.65
  2. TONNER C, TRUPIN L, YAZDANY J, CRISWELL L, KATZ P, YELIN E. Role of Community and Individual Characteristics in Physician Visits for Persons With Systemic Lupus Erythematosus Arthritis Care Res (Hoboken) [online] 2010 Jun, 62(6):888-895 [viewed 17 October 2014] Available from: doi:10.1002/acr.20125
  3. FARIA DA, REVOREDO LS, VILAR MJ, EULáLIA MARIA CHAVES M. Resilience and Treatment Adhesion in Patients with Systemic Lupus Erythematosus Open Rheumatol J [online] :1-8 [viewed 17 October 2014] Available from: doi:10.2174/1874312920140127001
  4. MANDAL M, TRIPATHY R, PANDA AK, PATTANAIK SS, DAKUA S, PRADHAN AK, CHAKRABORTY S, RAVINDRAN B, DAS BK. Vitamin D levels in Indian systemic lupus erythematosus patients: association with disease activity index and interferon alpha Arthritis Res Ther [online] 2014, 16(1):R49 [viewed 17 October 2014] Available from: doi:10.1186/ar4479
  5. TSOKOS GC. Drugs, sun and T cells in lupus Clin Exp Immunol [online] 2004 May, 136(2):191-193 [viewed 17 October 2014] Available from: doi:10.1111/j.1365-2249.2004.02455.x
  6. YUNG R, POWERS D, JOHNSON K, AMENTO E, CARR D, LAING T, YANG J, CHANG S, HEMATI N, RICHARDSON B. Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice. J Clin Invest [online] 1996 Jun 15, 97(12):2866-2871 [viewed 17 October 2014] Available from: doi:10.1172/JCI118743

Management - Specific Treatments

Fact Explanation
Multidisciplinary team management This is very important in managing patients with Systemic Lupus Erythematosus as it affect multi systems of the patients. This multidisciplinary team will need various specialist of the doctors according to the condition of the patient. eg: Physician- In managing the general condition of the patient Cardiologist/ cardiothoracic surgeon- in managing the cardiac complications like pericardial effusion, arrhythmias, valve problems Neurologist- In managing the cerebral lupus Rheumatologist- to manage arthritis and joint deformities Dermatologist- in managing the skin conditions Immunologist- In assessing the immunological status of the patient Nephrologist- In the presence of lupus nephritis Pulmonarologist- In presence of pulmonary complication Haematologist- In managing haematological complications (neurtropenia, leucopenia, thrombocytopenia and anaemia) , Pathologist- In assessing the histology ogf the patient Gynaecologist- in recurrent miscarriages Radiologist- In investigating the patient Gastroenterologist/ surgeon- in presence of gastrointestinal complication like mesenteric ischemia, bowel perforation Psychiatrist- in psychological counseling Other than doctors nursing care by nurses, physiotherapists, occupational therapists, social workers, relatives need to be included. Genetic specialist in genetic counseling. [1][2][3][4]5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]
Non Steroid Anti Inflammatory Drugs In the presence of arthralgia, arthritis, serositis, fever and other constitutional symptoms standard doses of Non Steroid Anti Inflammatory Drugs will be useful[36][37].
Topical corticosteroids Topical corticosteroids are helpful in managing the skin conditions in cutaneous lupus[38][39].
Antimalarial drugs Antimalarial drugs like chloroquine, hydroxychloroquine can be used in mild skin disease, fatigue and arthralgias where those symptoms cannot be controlled with NSAIDs[40][41]
Corticosteroids Various types of corticosteroids can be use to treat this condition. eg: Short course of oral corticosteroids in mild to moderate disease condition like presence of rash, serositis. Single intramuscular injections of long-acting corticosteroids or short courses of oral corticosteroids are useful in treating severe flares of arthritis, pleuritis or pericarditis. High dose of oral corticosteroids in lupus nephritis, cerebral lupus, severe haemolytic anaemia or thrombocytopenia.[42][43]
immunosuppressive drugs in addition to high dose of oral corticosteroids in lupus nephritis and cerebral lupus patients should be treated with immunosuppressive drugs like Cyclophosphamide, mycophenolate mofetil. Azathioprine like immunosuppressive drugs are used in maintaining remissions.[44][45]
Newer drugs like rituximab These are used in refractory cases of Systemic Lupus Erythematosus. It reduces the auto antibody levels by suppressing levels of CD20 positive B lymphocytes[46][47].
warfarin Patients with past history of previous thrombotic complications should be given life-long warfarin[48][49].
Management of pregnancy In Systemic Lupus Erythematosus As mentioned above multidisciplinary team management should be considered. Pre- pregnant counseling about maternal risks (eg; increased risk of flareup, risk of development of hypertension, pre-eclampsia, placental abruption) and foetal risk (eg: pre term deliverty, pre term rupture of membranes, intra uterine growth retardation, intra uterine foetal death and development of neonatal lpus syndrome). advice to conceive during remissions as there is less risk of flare up. Treat hypertension and closely monitor for the foetures of pre eclampsis and imminent eclampsia. Treat flare ups similer to non pregnant state. advice patients not to stop hydroxychloroquine if patient is already on, as it can precipitate flare up. Manage the pregnancy in a hospital with tertiary care facilities available. closely monitor maternal and foetal well being.[50][51]
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  2. VOULGARELIS M, KOKORI S, IOANNIDIS J, TZIOUFAS A, KYRIAKI D, MOUTSOPOULOS H. Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin Ann Rheum Dis [online] 2000 Mar, 59(3):217-222 [viewed 16 October 2014] Available from: doi:10.1136/ard.59.3.217
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  30. BAGAVANT H, FU SM. Pathogenesis of kidney disease in systemic lupus erythematosus Curr Opin Rheumatol [online] 2009 Sep, 21(5):489-494 [viewed 16 October 2014] Available from: doi:10.1097/BOR.0b013e32832efff1
  31. BARBER KA, JACKSON R. Neonatal lupus erythematosus: five new cases with HLA typing. Can Med Assoc J [online] 1983 Jul 15, 129(2):139-141 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1875279
  32. FORD HB, SCHUST DJ. Recurrent Pregnancy Loss: Etiology, Diagnosis, and Therapy Rev Obstet Gynecol [online] 2009, 2(2):76-83 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709325
  33. JONES HW, IRELAND R, SENALDI G, WANG F, KHAMASHTA M, BELLINGHAM AJ, VEERAPAN K, HUGHES GR, VERGANI D. Anticardiolipin antibodies in patients from Malaysia with systemic lupus erythematosus. Ann Rheum Dis [online] 1991 Mar, 50(3):173-175 [viewed 17 October 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1004368
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