Pediatric Rheumatology Online Journal

Vol 2, No. 2   2004 (134-138)

http://www.pedrheumonlinejournal.org

 

Addison’s disease in a child with systemic lupus erythematosus

Oliva Ortiz-Alvarez, Daniel L Metzger*, Peter N Malleson, David A Cabral,

Lori B Tucker, Ross E Petty

 

Key words: Addison’s disease, SLE, Childhood

 

Divisions of Rheumatology and Endocrinology*, Department of Pediatrics

University of British Columbia, and British Columbia’s Children’s Hospital

Vancouver, Canada.

 

O Ortiz-Alvarez MD MSc                         Research Associate

DL Metzger MD                                        Clinical Associate Professor

PN Malleson MBBS                                 Professor

DA Cabral  MBBS                                    Clinical Assistant Professor

LB Tucker MD                                           Clinical Associate Professor

RE Petty MD Ph.D.                                  Professor

 

Correspondence:

RE Petty, 1A19, British Columbia’s Children’s Hospital

4480 Oak St.

Vancouver V6H 3V4 BC Canada

 

Abstract

A 5-year-old girl presented with persistent hyponatremia after an episode of diarrhea and dehydration; a diagnosis of Addison’s disease was made. Nine months later, she developed systemic lupus erythematosus (SLE). Although adrenal failure has been related to the presence of antiphospholipid antibodies (APLA), and antibody-mediated autoimmune adrenalitis is the most common cause of primary adrenal insufficiency, neither adrenal cortex autoantibodies (ACA) nor APLA were found in our patient. Adrenal failure in association with SLE without APLA is extremely rare, (1-3) and has not previously been described in children.

 

Introduction

            Systemic lupus erythematosus is occasionally accompanied by autoimmune disorders of endocrine glands, most commonly the thyroid, but rarely the adrenal glands.  Adrenal failure has been described in three adults with SLE, (1-3) and in three children (4-7) and in several adults with antiphospholipid syndrome, (8-11) a condition that occurs most frequently in patients with SLE. We describe a young child with Addison’s disease and SLE in the absence of either antiphospholipid or adrenal antibodies.

 

Case Report

            A 5 3/12 year-old girl of East Indian origin was admitted to hospital in October 1995 for investigation of persistent hyponatremia following an episode of diarrhea, vomiting and dehydration and a one-month history of fatigue. Neither salt craving nor increased skin pigmentation was noted. Two years previously she had an episode of acute thrombocytopenia that resolved completely with six weeks of treatment with prednisone (1 mg /kg/day). Results of tests for antinuclear antibodies were not available.

            A diagnosis of Addison’s disease was established by the presence of hyponatremia (125 mmol/L), an elevated plasma ACTH level of 281 pmol/L (normal 2 – 13) and a low plasma cortisol level of <31 nmol/L (normal 140-700), with no increase 60 min after ACTH administration, and an elevated upright renin of 7.86 ng/L/sec (normal 0.28 - 1.1). Normal levels of 17-hydroxyprogesterone (17-HP 0.6 nmol/L; normal <3), and dehydroepiandrosterone sulfate <0.14 nmol/L (normal 0 – 0.14) excluded the possibility of congenital adrenal hyperplasia. Normal levels of very long-chain fatty acids excluded the remote possibility of adrenoleukodystrophy. Adrenal antibodies were not detectable by indirect immunofluorescence. She was treated with hydrocortisone and fludrocortisone, with resolution of her symptoms. After 7 months of follow-up by an endocrinologist, she developed persistent anemia and the possibility of pernicious anemia was entertained but not confirmed.

            Six weeks later the patient developed left leg pain without morning stiffness. Physical examination showed restricted range of motion (ROM) of the left hip. Radiographs were normal, but ultrasonography demonstrated a small amount of intra-articular fluid in the hip. Laboratory investigations revealed Hgb of 73 g/L (normal 118-140), a white blood cell count of 8.89 x 109 /L (normal 6 - 16) with a normal differential, and a platelet count of 191 x 109 /L (normal 180-440). The erythrocyte sedimentation rate was 134 mm/hr (normal <21). Antinuclear antibodies (ANA) were present in a low titer of 1:40, and a test for antibody to double-stranded DNA using Crithidia luciliae was weakly positive. Urinalysis was normal. Radiographs of the hip demonstrated no bony abnormalities. The hip arthritis was initially attributed to transient synovitis of childhood, and symptoms resolved after 48 hrs of naproxen therapy. No other joints were involved.   Ten months later, she was noted to have a sun-sensitive malar rash, a fever of 38.6 0 C, and she had another transient episode of "irritable hip" on the right side. The Hgb was 75 g/L with a high reticulocyte count, and erythrocyte morphology was suggestive of hemolysis (anisocytosis, poikilocytosis). Howell-Jolly bodies were present indicating splenic hypofunction. The platelet count was 97 x109 /L. ANA were present in a titer of 1:160, Anti-ds-DNA measured by a radioimmunoassay was 26.4 (normal < 3.5), anti-Sm was 172 U/L (normal < 45), and anti-SSB was 54 U/L (normal <44). Coombs’ test demonstrated IgG and C3 on erythrocytes. IgG and IgM anticardiolipin levels measured by an enzyme linked immunosorbent assay (ELISA) were not increased. Liver enzyme levels and urinalysis were normal. A diagnosis of SLE was made according to the classification criteria of the American College of Rheumatology (12) (photosensitive malar rash, arthritis, positive ANA and presence of anti-dsDNA, and Anti-Sm). Treatment with prednisone was instituted and over a period of 3 years follow-up she has responded well with no further episodes of hip pain, or other overt manifestations of SLE.

 

Discussion

            In retrospect, this child had evidence of evolving SLE with the development of acute thrombocytopenia two years prior to the onset of adrenal failure, followed by episodic hip synovitis after the Addison’s disease became manifest. Unfortunately appropriate specific serologic test for SLE (anti-DNA, anti-extractable nuclear antigens antibodies) were not performed at the time idiopathic thrombocytopenic purpura (ITP) was diagnosed.

            In patients with SLE, the incidence of autoimmune thyroiditis may be increased (13), but other endocrine diseases including Addison’s disease appear to be rare. In patients with Addison’s disease rheumatic diseases are also very uncommon. In a group of 14 children with Addison’s disease who were followed for an average of 10 years, one developed diabetes type 1 and three developed hypoparathyroidism, but none developed a rheumatic disease. (14)

            Addison’s disease in children is commonly associated with anti-adrenal antibodies directed to the enzyme 21-hydroxylase. (15) In a 10-year-old child, Addison’s disease characterized by fatigue, irritability, headache and pain in the limbs, neck and chest preceded by four months, the development of primary antiphospholipid syndrome characterized by thrombosis of the inferior vena cava and iliac veins; SLE was not present. (6) Chronic thrombocytopenia may occur in association with APLA; however the development of ITP two years prior to Addison’s disease presentation may have represented the unrecognized onset of SLE.

            This is the first report of Addison’s disease in a child with SLE in the absence of antiphospholipid antibodies. Although we cannot prove that the Addison’s disease is specifically related to SLE in this child, this would seem to be the most likely explanation, however the possibility of coincidental occurrence cannot be excluded.

            This report stresses the importance of considering SLE in each child with ITP, and indicates the need to be alert to the possibility of endocrine disease developing in children with autoimmune disease.

 

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