Systemic Lupus Erythematosus

A CASE REPORT AT FAHCQMU Systemic Lupus Erythematosus (SLE): Frequently missed at first visit CASE REPORT BY: Dr. Mohan Khadka, MBBS (KU, Nepal), ECFMG certified (USA), MD resident, CQMU, Chongqing, China TUTOR: Prof. Xiaohong Tao, Head of Department of Gastroenterology, First Affiliated Hospital of CQMU

ABSTRACT Background: Frequently many SLE cases especially in young women are missed in the first visit because of which patient suffers in terms of morbidity, economic expenditure and time. Methods: We had reported a case of a 30-year-old woman patient on antitubercular treatment (ATT) in local hospital for false diagnosis of Pulmonary tuberculosis at First Affiliated Hospital of Chongqing Medical University (FAHCQMU) with complaints of abdominal pain, chest pain, photosensitive skin rashes, fatigue, malaise, multiple joint pain, nausea, anorexia, loss of weight, amenorrhea and various other laboratory abnormalities. Further investigations at FAHCQMU, lead to a diagnosis of Systemic Lupus Erythematosus (SLE). A literature search, using the key words "Systemic Lupus Erythematosus", "Tuberculosis", “Amenorrhea” and relationship among them was undertaken. Results and Conclusions: The case was further investigated in line of any disease which could have been presented with multisystem involvement and was found to be SLE. The first diagnosis of Tuberculosis at local hospital was declined here with regard to the lack of adequate laboratory support. Steroid was started and good improvement was seen. SLE can involve any organ system. It is important that the physician, who treats patient as a whole, must rule out SLE when a straightforward diagnosis is associated with inexplicable multiple concomitant abnormalities.

CASE REPORT A 30-year-old Chinese woman, previously well, came to the FAHCQUMS complaining of a 4 days history of new onset of skin rashes with fever. On further inquiry she revealed that she was on Anti-tubercular treatment (ATT) Regime for 4 days. She was diagnosed as pulmonary tuberculosis a half

month before when she presented at the local hospital with complaints of low grade fever,

fatigue, malaise, myalgia, arthralgia, anorexia, significant weight loss, occasional cough and non specific chest and abdominal discomfort for 4 months. According to reports from local hospital, she underwent CT abdomen/chest and the findings were cholelithiasis with multiple small sized stones, splenomegaly and mild pleural effusion with negative

ascites. Echocardiography was also done and was found to be mild pericardial effusion. Antibody against Tuberculosis was equivocal (+/-). PPD test was not performed. At local hospital, she was diagnosed as Tubercular pleuritis and peritonitis for which ATT with Isoniazid and Rifampicin was started. Cholelithiasis was regarded as incidental finding. She developed sudden skin rashes with high grade fever the day after she started ATT and was given dexamethasone for two days for the purpose. After two days she came to FAHCMU for not being getting better for her complaints at local hospital. Her past medical history was uneventful for diabetes, hypertension, tuberculosis, autoimmune diseases, respiratory illness and cancer. She denied smoking, alcohol and illicit drug use. Her family history was unremarkable for autoimmune disorders. She is married and living with her husband and a daughter. She is also suffering from amenorrhea for last 3 months. She had regular menstruation of 4-6/30 until she developed amenorrhea for last 3 months. She had menarche at the age of 13. When examined at the time of admission, she was fully conscious, well oriented to time, place and person but looking lethargic and moderately cachexic. She was mildly febrile with 37.5 degree Celsius; her pulse rate was 90 beats per minute, and her blood pressure was 100/64 mmHg. She had a few skin eruptions most of which were on the process of healing. A few left upper cervical and supraclavicular lymphnodes were palpable and mild tenderness was present. Her eyes were normal on examination except pallor. Her chest sounds were clear with no friction rubs, and she had no murmurs or rubs. Her abdomen was moderately hard with guarding and rigidity, mild tenderness on palpation with mild rebound tenderness was present. No liver, spleen and any masses were palpable and percussion findings were also similar. Normal bowel sound was present. She had no vaginal discharge, cervical motion tenderness, or adnexal masses. Her uterine size was normal. Her extremities showed no joint swelling or tenderness. Neurologically, she was unremarkable. Laboratory studies disclosed the following values: sodium 128 mmol/L(normal 136 – 145 mmol/L), potassium 2.8 mmol/L(normal 3.5 – 5.2 mmol/L), chloride 105 mmol/L, bicarbonate 15 mmol/L(normal 22 – 32 mmol/L), blood urea nitrogen 8.1 mg/dL, creatinine 41 µmol/L(normal 45 – 84 µmol), glucose 84 mg/dL, aspartate aminotransferase 180 U/L (normal 0–40 U/L), alanine aminotransferase 78 U/L (normal 0–40 U/L), protein 68 g/L, albumin 23 g/L (normal 35 – 55 g/L) , calcium 1.90 mmol/L(normal 2.03 – 2.54 mmol/L) and total bilirubin 1.3 mg/dL (normal 0.2–1.3 mg/L). A complete blood count showed a white cell count of 2.42 x 109/L (normal 3.70 – 9.20 x 109/L) with a differential cell count of neutrophils 56.7%, lymphocytes 32.2% monocytes 10.30%, Eosinophils 0.40%, Basophils 0.40%. Hemoglobin was 83 g/L (113.0 – 151.0 g/L), hematocrit 23.9% (normal 33.5 - 45%),RBC count 3.28 x 1012/L (normal3.68 x 1012/L-5.13 x 1012/L) and platelets 91 x 109/L. MCV 72.9 (82.6-99.1 fL), MCH 25.3 (26.9-33.3 Pg) and MCHC 347 ( 322-362 G/L). Urinalysis showed cloudy urine with protein 2+, a white cell count of 25/ul (normal 0 – 15 /ul), EC 15/uL (normal 0 – 9/uL) N-RBC 25 (normal 0 – 18/Ul). Urine pregnancy test was negative. A computed tomographic (CT) with contrast and USG scan of the abdomen showed evidence of multiple small sizes gallbladder stones and also benign hepatic angioma measuring 33 x 18 mm. Pelvic USG also showed no detectable pathology.

The patient was admitted to the Gastroenterology Unit at FAHCMU with differential diagnoses of peritonitis, pleuritis either due to tuberculosis or cancer or systemic autoimmune disease. Additional diagnosis of ATT induced hypersensitivity reactions for her recent development of skin rashes with fever was made and cholelithiasis, benign hepatic angioma were defined as coincidental findings out of her systemic manifestations for last 4 months. ATT was stopped and was planned on high nursing diet along with routine nursing care. Chest X-ray and PPD test were done and the result came against tuberculosis. Connective tissue workup showed a antinuclear antibody (ANA) titer 1:320, anti-double-stranded DNA antibody positive with 1:32 titer, anti-Smith antibody positive, anti-ribonucleoprotein positive, anti-SSA and anti-SSB negative, anticardiolipin antibodies negative, Lupus anticoagulant was negative. Tests for Syphilis, HCV, and HIV were all negative. Tumer markers like CEA, CA-125 and AFP came negative. Endocrine hormonal assay were ordered on day 8 after admission for serum levels of FSH, LH, estradiol and progesterone and came to be normal at low range except testosterone which was reduced below normal limit. In addition, serum thyroid hormones; T3, T4 and TSH were also checked but the result came within normal range. Serum antibodies against thyroid tissue were negative. A diagnosis of SLE was made on second day of admission, and oral prednisolone, a steroid with the dose of 1 mg/kg/day in two divided doses was started. Repeated progress reports of morning round on everyday showed significant improvement clinically. On day 16 of admission, she said that nausea and vomiting disappeared and appetite went on better and started gaining weight too. She did not have chest and abdominal pain and on abdominal palpation, the abdomen was relatively softer and less tender than previous findings. X-ray chest on day 16 of admission (2009/03/30) was done for her complaint of dyspnea which showed only mild lung infiltrates. On 29 days of admission, she showed significant progress in terms of morbidity. She gained weight of 4 kg during hospital stay and it increased from 34 kg at the time of admission to 38 kg at the time of discharge in absence of ascites, pleaural effusion or any edema. No side effects of prednisolone were observed during the hospital stay of one month. Her all previous complaints were disappeared except amenorrhea and she was discharged with the advice of continuing prednisolone 30 mg in two divided doses and asked her to come back in follow up after a week. The working diagnosis at the time of discharge was SLE improved on prednisolone and further plan was to continue prednisolone with tapering dose by 5 mg every week until minimum 10 mg/day dose would be reached which would be advised to be maintained for almost 6 months.

DISCUSSION Systemic lupus erythematosus is a multisystemic autoimmune disorder characterized by a broad range of manifestations and the finding of antibodies in the blood directed against one or more components of cell nuclei. It has a definite female predominance (9:1; F: M), especially after the onset of puberty, but has been known to occur in children as young as 3 years of age. The most common areas of involvement are the joint and cutaneous system, with nonspecific complaints of fever, malaise and fatigue, and renal disease. The initial manifestation, however, can involve any organ system either singly or in combination, which frequently makes diagnosis difficult. The American Rheumatism Association recommends 4 of the following 11 revised criteria for the diagnosis of SLE: malar rash,

discoid rash, photosensitivity, oral ulcers, arthritis, serositis, renal disorder, neurologic disorder, hematologic disorder, immunologic disorder on serologic testing, and antinuclear antibodies. Our case illustrates the mutable manifestations of SLE and nearly misdiagnosed as pulmonary tuberculosis. In retrospect, although our patient fulfilled the ARA criteria for the diagnosis of lupus on admission, the initial impression was just possible tubercular peritonitis or pleuritis and hypersensitivity reactions to antitubercular medications possibly isoniazid. As X-Ray of Chest and PPD showed negative result for Tuberculosis, then further work up was proceeded to establish the cause for her multisystem complaints. Fortunately, fortuitous screening with ANA titers for connective tissue disease was made for a timely diagnosis of SLE with special effort of the treating doctors. TB and drug induced lupus were ruled out. The skin rashes were probably due to the result of ATT induced hypersensitivity reactions which were disappeared after the discontinuation of ATT with admission in the department. Our patient had multiorgan involvement of SLE, namely, hematologic, renal, integumentary and rheumatological. At the time of hospital visit as the patient was on Isoniazid, Rifampin, one could think of Isoniazid induced Lupus as differential diagnosis but given her 4 months complaints of multysystem involvement before she started taking Isoniazid which she just took for few days did not go in favor of drug induced Lupus as the data says that it takes months to develop it. For her amenorrhea of 3 months history (LMP 2008/12/18), the possibility of autoimmune induced thyroiditis was suspected. However serum T3, T4 and TSH values came within normal range except rT3 which was slightly decreased and more over serum antibodies against thyroid gland came out to be negative which clearly rule out the possibility. The other possibility for amenorrhea could be due to malnutrition secondary to anorexia as a result of SLE in the patient. We can even think of the possibility of direct casual relationship between SLE and amenorrhea which could be due to subclinical or clinical autoimmune ovarian damage as it has been described in literature. In our case too, serum FSH, LH, estrogen and progesterone level, all are in lower normal range except testosterone which is reduced below normal limit which may point to the possibility of suppression of hypothalamo pituitary ovarian axis due to severe SLE.

CONCLUSION SLE can involve any organ system. It is important that the physician, who treats patients as a whole, should suspect SLE as a potential differential diagnosis especially in young woman presenting with severe constitutional symptoms e.g. loss of appetite and significant loss of weight including multisystem involvement simulating tuberculosis or cancer. The association between SLE and amenorrhea needs to be well defined by medical research in future at molecular level too.

REFERENCES 1.

Mills JA. Systemic lupus erythematosus. N Engl J Med 1994; 330: 1871–9.

2.

Block SR, Winfield JB, Lockshin MD, D’Angelo WA, Christian CL. Studies of twins with systemic lupus erythematosus. A review of the literature and presentation of 12 additional sets. Am J Med 1975; 59: 533–55.

3.

Wallace DJ. The clinical presentation of systemic lupus erythematosus. In: Wallace DJ, Hahn BH, editors. Dubois’ lupus erythematosus. 5th ed. Baltimore: Lippincott Wilkins & Wilkins: 1997; 627.

4.

Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271–7

5.

Reifenstein EC, Reifenstein GH. A variable symptom complex of undetermined etiology with fatal termination. Arch Intern Med 1939; 63: 552–74.

6.

Saab S, Corr MP, Weisman MH. Corticosteroids and systemic lupus erythematosus pancreatitis. A case series. J Rheumatol 1998; 25: 801–6.

7.

Petri M. Pancreatitis in systemic lupus erythematosus: still in search of a mechanism. J Rheumatol 1992; 19; 1014–6.

CASE REPORT BY: Dr. Mohan Khadka, MBBS (KU, Nepal), ECFMG certified (USA), MD resident, CQMU, Chongqing, China