Primary Sjogren syndrome presenting with quadriparesis

INTRODUCTION

Hypokalaemic periodic paralysis (HPP) is a clinical syndrome of transient, generalised muscle weakness occurring in the context of low serum potassium levels.^[1] Although uncommon, it is important to distinguish between hereditary and acquired forms, as secondary HPP can arise in a variety of metabolic or endocrine conditions.^[2] Among the acquired causes, renal tubular acidosis is especially relevant because it produces a characteristic non-anion gap metabolic acidosis accompanied by renal potassium wasting.

Distal renal tubular acidosis (RTA), in particular, reflects impaired secretion of hydrogen ions in the distal nephron. This defect may be genetic or associated with systemic diseases, including autoimmune disorders such as Sjögren syndrome, systemic lupus erythematosus, and rheumatoid arthritis.^[3] Proximal RTA, by contrast, is caused by deficient bicarbonate reclamation in the proximal tubule.^[4] A combination of biochemical testing, urine studies, and clinical context is typically required to differentiate between these entities.^[5]

Here, we report a patient who presented repeatedly with severe hypokalaemic weakness and was ultimately found to have distal RTA secondary to previously unrecognised primary Sjögren syndrome.

CASE REPORT

A 30-year-old woman presented with progressive generalised weakness, reduced appetite, oral dryness, difficulty swallowing solids without water, pruritic eyes, constipation, and a malar rash for 6 months. During the preceding 3 months, she experienced two episodes of sudden-onset weakness affecting all four limbs, without bladder, bowel, bulbar or neck muscle involvement. On one of these occasions (April 2024), she required ventilatory support. Severe hypokalaemia (serum potassium 1.9 mEq/L) had been identified at that time, and she recovered with potassium supplementation, though the underlying cause remained unexplored.

She returned in August 2024 with another acute episode of quadriparesis, more pronounced in the lower limbs and affecting proximal muscle groups. She denied vomiting or diarrhoea, and there was no family history of similar episodes. Her vital signs revealed tachycardia and postural symptoms, with a blood pressure of 110/70 mmHg. Motor strength was 2/5 in the lower limbs and 3/5 in the upper limbs.

Investigations demonstrated persistent hypokalaemia (3 mEq/L) and a normal anion gap metabolic acidosis (pH 7.32; Na⁺ 135 mEq/L; bicarbonate 12.5 mEq/L; Cl^- 109 mEq/L; PCO₂ 24 mmHg and anion gap 12). She had an alkaline urine (pH 7.5) and a positive urine anion gap. Urinalysis showed no proteinuria or haematuria; 24-h urinary protein was 372 mg/day. Urinary potassium excretion was markedly elevated (494 mmoL/day; normal <125), while phosphate and uric acid excretion were within reference limits.

Autoimmune testing revealed antinuclear antibodies positivity (1:100, speckled pattern) and strongly positive anti-sjogren’s syndrome A (anti-SSA), anti-sjogren’s syndrome B (anti-SSB), and Ro-52 antibodies. Anti-double-stranded DNA titres were mildly elevated (1:10). Lip biopsy [Figure1 a and b] demonstrated periductal lymphocytic infiltration, salivary gland inflammation and ductal dilatation, consistent with autoimmune sialadenitis. Although the Schirmer test did not show reduced tear production, her elevated IgG levels and positive rheumatoid factor, combined with serological and histological findings, supported a diagnosis of Sjögren syndrome. Tuberculosis screening through Quantiferon-TB Gold was negative.

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Figure 1:

(a) H&E (Hematoxylin & Eosin Stain,100×): arrows showing periductular lymphocytic infiltrate within inflamed salivary gland and duct dilatation, (b) Immunohistochemistry using Leukocyte common Antigen (LCA) stain: arrow highlighting periductular lymphocytic infiltrate ,100×.

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She received intravenous potassium supplementation (200 mEq/day), resulting in near-complete recovery of muscle strength within 24 h. Subsequently, she was started on potassium citrate syrup (60 mL/day, equivalent to 120 mEq/day), low-dose corticosteroids, hydroxychloroquine and two doses of rituximab (1 g each). Her serum potassium stabilised between 4.0 and 4.5 mEq/L on follow-up, and she was maintained on long-term potassium and alkali therapy to prevent recurrent weakness and complications of chronic metabolic acidosis.

DISCUSSION

Autoimmune diseases are among the most frequent systemic causes of distal RTA, and Sjögren syndrome is a well-recognised contributor.^[1] Serological markers, particularly anti-SSA/Ro and anti-SSB/La, play a central role in diagnosis, with SS-A being more sensitive and SS-B more specific for Sjögren syndrome.^[6] Histopathological examination of minor salivary glands adds further diagnostic value, especially when sicca symptoms are subtle or absent.

Sjögren syndrome is characterised by chronic lymphocytic infiltration of the exocrine glands, most commonly affecting middle-aged women.^[7] Extraglandular manifestations may involve the renal, neurologic, hepatic, cutaneous or pulmonary systems.^[8] Renal involvement typically presents as distal RTA due to impaired hydrogen ion secretion, often attributed to dysfunction or loss of the H⁺-ATPase pump in the collecting duct. Distal RTA may remain asymptomatic until complications such as hypokalaemia, nephrocalcinosis or recurrent muscle weakness occur .^[6]

Hypokalaemia in distal RTA is common and, in some cases, may precede classical sicca manifestations, delaying recognition of Sjögren syndrome.^[9] Episodic quadriparesis is a known but relatively uncommon presentation and can occasionally be the initial clinical clue.

Management of hypokalaemic paralysis involves rapid potassium repletion, often at doses of 0.5–1.0 mEq/kg, followed by long-term correction of acidosis with potassium citrate or bicarbonate.^[10] Treatment of the underlying autoimmune disorder, including immunosuppressive agents such as corticosteroids, hydroxychloroquine or rituximab, may improve renal tubular function and reduce recurrence.

In our patient, the constellation of sicca symptoms, serological positivity and confirmatory lip biopsy findings fulfilled the American-European Consensus Group criteria for Sjögren syndrome, despite a non-contributory Schirmer test. Early recognition allowed timely intervention, preventing further episodes of life-threatening hypokalaemia paralysis.

CONCLUSION

Sjögren syndrome should be considered a potential cause of hypokalaemia and recurrent HPP, especially in young women. Because renal tubular involvement may precede overt sicca symptoms, clinicians must maintain a high degree of suspicion when encountering persistent hypokalaemia with a normal anion gap metabolic acidosis. Prompt identification and treatment of the underlying disorder, along with correction of potassium and bicarbonate deficits, can prevent severe neuromuscular complications and long-term metabolic consequences.