Hypokalaemia and severe acute power loss: an unusual presentation of Sjögren’s Syndrome

P A Henriksen¹ and M King² 

¹Department of Cardiology, Western General Hospital and ²Department of Renal Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK.

Correspondence to:

Dr PA Henriksen, Department of Cardiology, Western General Hospital, Crewe Road South EH4 2XU, Edinburgh, UK

Email: p.henriksen@ed.ac.uk

SMJ 2006 51(2): 54

Abstract

Acute paralysis in the context of hypokalaemia is the presenting feature of a rare group of heterogeneous disorders including the familial periodic paralyses and renal tubular acidosis. Hypokalaemic paralysis has previously been described as the presenting feature of Sjögren’s Syndrome. In this report we present a patient with hypokalaemic paralysis, distal renal tubular acidosis and features suggestive of Sjögren’s Syndrome.

Keywords: renal tubular acidosis, Sjögren’s Syndrome, hypokalaemia, paralysis

Case Report

A 49-year old caucasian woman presented with 3 days of progressive power loss affecting all four limbs. She had generalised muscle aching and described lethargy over the preceding month. She had been on thyroxine replacement therapy for 3 years and there was no preceding history of diarrhoea, laxative or diuretic abuse.

On admission she was apyrexial, with a pulse of 72/min, and blood pressure 125/80 mmHg. Neurological exam revealed severe symmetrical weakness (grade 2/5) throughout proximal and distal muscle groups with preserved muscle bulk. Reflexes were preserved and there was no sensory deficit. Respirations were shallow and the FVC was diminished at 1.8 litres. Facial power was also affected although ocular movement was intact. Chest and abdominal examinations including dipstick urinalysis for blood and protein were unremarkable. Lymph nodes were normal and there was no parotid or thyroid gland enlargement. An electrocardigram revealed T wave flattening, prominent U waves and marked QT interval prolongation (Figure I). The chest X-ray was normal.

Initial blood tests were as follows; haemoglobin 11.8 g/dl, white cell count 8800/mm³, platelets 217,000/mm³, Na 146 mmol/l, K 1.6 mmol/l, urea 4.1 mmol/l creatinine 88 mmol/l, albumin 46 g/l, Ca  1.89 mmo/l, PO₄ 0.39 mmol/l, Mg 1.24mmo/l, venous bicarbonate 9 mmol/l, chloride 122 mmol/l, calculated anion gap 14.7, H+ 61.9 nmol/l, CO₂ 2.67 kPa, PO₂ 13.23 kPa. Thyroid and liver function tests were within normal limits. A spot urine pH measurement was 7.05 and a 24 hour collection on admission of 4.3 litres had a total sodium of 197 mmol, total potassium of 73 mmol, total calcium 3.4 mmol and phosphate 23.6 mmol with a measured osmolality of 176 mosm/l. Simultaneous plasma osmolality was 291 mosm/l giving a calculated trans-tubular potassium gradient of 15.5 (Table I). Amino acids were not detected. Ultrasonography of the kidneys was normal with no evidence of nephrocalcinosis on plain X-ray.

Potassium and phosphate replacement were initially given through a central vein. Cardiac rhythm and respiratory function were monitored closely. Potassium was infused at 10 mmol/hour for the first day and following this there was a significant improvement in power although the patient was unable to mobilise independently until 3 days post-admission and the serum K⁺ level did not rise above 2 mmol/l until the second day. Oral sodium bicarbonate supplements were introduced cautiously when the potassium concentration had risen above 3.0 mmol/l and by discharge the patient had stabilised on 2 g/day of sodium bicarbonate and 24 mmol/day of oral potassium.

In view of the profound hypokalaemia and acidosis with complete failure to acidify the urine, a diagnosis of distal renal tubular acidosis was made. An autoantibody screen revealed positive anti-nuclear antibodies (1:640 nucleolar, 1:40 speckled) and high titres of anti-Ro and anti-La antibodies (greater than 100meq). There was a polyclonal increase in IgG but no evidence of serum or urinary paraproteins. The patient had a renal biopsy 2 months after discharge. Glomeruli, vessels and tubules were intact with a mild chronic interstitial infiltrate of plasma cells and occasional eosinophils. During follow up she reported herself as being well with no recurrence of her paralytic symptoms.

Given the highly suggestive serology and characteristic interstitial plasma cell infiltrate a diagnosis of Sjögren’s Syndrome was made. The patient denied symptoms of sicca syndrome and quantitative tests of lacrimation or salivary gland biopsy were not performed.

Discussion 

The differential diagnosis of a metabolic acidosis with a normal anion gap is relatively short with the majority of cases being caused by gastrointestinal loss of bicarbonate (diarrhoea) or renal tubular acidosis. Distal RTA may be a primary disorder but more commonly arises within the context of paraproteinaemia, medullary sponge kidney, nephrocalcinosis, obstructive uropathy and autoimmune disease ¹ .

The diagnosis is suggested in patients with a metabolic acidosis and inappropriately alkaline urine (pH > 5.3) in the absence of severe volume depletion. The resulting reduced potassium resorption in the face of marked hypokalaemia was illustrated by the increased transtubular potassium gradient (TTKG).

Renal tubular acidosis (RTA) is caused by a renal tubular defect resulting in failure to acidify the urine and a systemic acidosis. Several mechanisms of urinary acidification failure have been described. In some instances there is an inappropriate reduction in proximal tubular bicarbonate reabsorption (Type 2, proximal RTA). In distal RTA (Type 1) there is an inability to secrete H+ ions against the steep luminal pH gradient. This most commonly results from failure to transport H+ ions into the lumen owing to absent or dysfunctional H+-ATPase pumps ² . Linkage analysis has identified mutations in a subunit of the apical H+-ATPase in patients with hereditary distal RTA associated with sensorineural deafness ³ .

Distal RTA should be treated with alkali therapy even in the absence of hypokalaemia. This will protect the bones from the effects of systemic acidosis thereby preventing osteomalacia (bones act as a buffer for acidosis). In addition, treatment may reduce the risk of renal calculi and progression of nephrocalcinosis. In children treatment is particularly important to allow normal growth.

Sjögren’s Syndrome may occur as a primary disorder or part of a connective tissue disease such as systemic lupus erthyematosus. Dry mouth, dry eyes, tiredness and arthralgia are key features although the broad spectrum of clinical manifestations including pulmonary, liver, thyroid and renal involvement have led to debate over a single set of diagnostic criteria ^4;5 . There is a recognised association between distal RTA and Sjögren’s Syndrome ^6;7 . Distal RTA may precede the other clinical features of Sjögren’s Syndrome and hypokalaemic paralysis with respiratory arrest have previously been described as the presenting features ⁸ . Autoimmune investigations for Sjögren’s Syndrome should therefore be performed in any patient presenting with hypokalaemic paralysis even in the absence of sicca syndrome.

Reference 

   1.   Chan JC, Alon U. Tubular disorders of acid-base and phosphate metabolism. Nephron. 1985;40:257-279.

   2.   DeFranco PE, Haragsim L, Schmitz PG, Bastani B. Absence of vacuolar H(+)-ATPase pump in the collecting duct of a patient with hypokalemic distal renal tubular acidosis and Sjogren's syndrome. J Am Soc Nephrol. 1995;6:295-301.

   3.   Karet FE, Finberg KE, Nelson RD et al. Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness. Nat Genet. 1999;21:84-90.

   4.   Manthorpe R, Asmussen K, Oxholm P. Primary Sjogren's syndrome: diagnostic criteria, clinical features, and disease activity. J Rheumatol Suppl. 1997;50:8-11.

   5.    Diagnosis of Sjogren's syndrome. Lancet. 1992;340:150-151.

   6.   Zimhony O, Sthoeger Z, Ben David D, Bar KY, Geltner D. Sjogren's syndrome presenting as hypokalemic paralysis due to distal renal tubular acidosis. J Rheumatol. 1995;22:2366-2368.

   7.   al Jubouri MA, Jones S, Macmillan R, Harris C, Griffiths RD. Hypokalaemic paralysis revealing Sjogren syndrome in an elderly man. J Clin Pathol. 1999;52:157-158.

   8.   Fujimoto T, Shiiki H, Takahi Y, Dohi K. Primary Sjogren's syndrome presenting as hypokalaemic periodic paralysis and respiratory arrest. Clin Rheumatol. 2001;20:365-368.

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