Hypokalemic Periodic Paralysis in a Patient With Primary Sjögren’s Syndrome and Distal Renal Tubular Acidosis: A Case Report

Abstract

Introduction:

Hypokalemic periodic paralysis (HPP) is a severe yet reversible neuromuscular condition precipitated by profound hypokalemia. Autoimmune disorders can exacerbate renal potassium loss resulting in abrupt muscle weakness. Primary Sjögren’s syndrome (pSS), an autoimmune disease characterized by exocrine gland insufficiency, can lead to renal tubular dysfunction and episodes of HPP when distal acidification is compromised.

Case presentation:

A 40-year-old woman was admitted with rapidly progressive, painless quadriplegia for over 2 days. Laboratory tests revealed critical hypokalemia (1.4 mEq/L), metabolic acidosis, and alkaline urine pH, which was consistent with type 1 distal renal tubular acidosis (dRTA). Serologic studies confirmed pSS. Corrective measures included intravenous potassium chloride and sodium bicarbonate along with immunomodulation with intravenous methylprednisolone, followed by oral prednisolone.

Discussion:

The patient’s presentation illustrates how autoimmune-mediated renal tubular dysfunction can precipitate HPP. Failure of distal acid excretion impairs potassium handling, amplifying the risk of potentially life-threatening neuromuscular collapse. Stabilization requires meticulous electrolyte repletion and treatment of the underlying autoimmunity. Restoration of serum potassium levels, acid-base balance, and targeted immunosuppression resulted in rapid clinical improvement.

Conclusion:

An accurate diagnosis of HPP secondary to dRTA and Sjögren’s syndrome requires high clinical suspicion. Prompt recognition and intervention, including immunotherapy and balanced electrolyte replacement, can prevent profound neuromuscular complications and improve patient outcome.

Introduction

Periodic paralysis refers to a group of neuromuscular syndromes characterized by episodic flaccid weakness, typically resulting from serum electrolyte imbalances, especially potassium. ¹ Hypokalemic periodic paralysis (HPP) is often hereditary and may be acquired through renal or gastrointestinal potassium loss, endocrine disorders, or autoimmune renal involvement. ² Distal renal tubular acidosis (dRTA) is a rare but important differential in cases of unexplained hypokalemia. ³ It is caused by defective hydrogen ion secretion in the collecting duct due to impaired function of α-intercalated cells. Paradoxically, this leads to systemic metabolic acidosis with alkaline urine and compensatory renal potassium wasting. Unlike proximal RTA, dRTA is not associated with bicarbonate reabsorption defects and presents with normal or mildly elevated creatinine. ⁴ Autoimmune diseases, particularly primary Sjögren’s syndrome (pSS), may cause tubulointerstitial nephritis and dRTA via lymphocytic infiltration or autoantibody-mediated injury (eg, anti-carbonic anhydrase II, anti-SSA/SSB).^5,6 While pSS is classically associated with sicca symptoms, renal involvement may precede or occur in their absence. ⁷ Hypokalemia due to dRTA can, in turn, precipitate HPP, which may be the presenting feature of occult systemic disease. ⁸ Herein, we report a case of HPP as the first manifestation of pSS-associated dRTA in a previously undiagnosed patient.

Case Report

A 40-year-old woman presented to the emergency department with sudden, painless weakness in all the limbs. Progression from difficulty walking to near-complete quadriplegia occurred over 2 days, without sensory deficits or autonomic dysfunction. She denied diuretic or steroid use and had no recent fever, diarrhea, or insect bites. There was no history of diabetes mellitus, hypertension, nephrolithiasis, oral contraceptive use, excessive calcium or vitamin C intake, or alcohol abuse. She did, however, mention chronic dryness of her eyes and mouth for nearly a year, accompanied by intermittent, symmetrical arthralgias in her wrists and hands that were non-deforming. Previous medical records did not reveal nephrolithiasis or previous paralysis. On physical evaluation, she was alert, her blood pressure was 118/70 mmHg, her pulse was 70 beats per minute, her respiratory rate was 18 breaths per minute, and her body temperature was normal. Deep tendon reflexes were not elicited in any of the limbs.

Laboratory tests revealed significant hypokalemia (serum potassium 1.4 mEq/L). Given her history of dryness in the eyes and mouth, Serologic markers for Sjögren’s syndrome was investigated. The initial autoimmune screening indicated a strongly positive anti-Ro (SS-A) of 92.5 U/mL and anti-La (SS-B) of 78.3 U/mL, with an otherwise negative anti-dsDNA. Schirmer’s testing in both eyes measured under 5 mm in 5 minutes. Using the ACR/EULAR 2016 classification criteria, ⁹ the patient scored 4 points, satisfying the threshold for pSS. Additional arterial blood gas analysis revealed a pH of 7.26 and a serum bicarbonate level of 13 mEq/L, consistent with a high-anion-gap calculation initially; however, a more detailed evaluation showed a normal anion gap of 12 with an alkaline urine pH of 7.6, positive urinary anion gap, and concurrent renal potassium wasting.

Additional evaluations included normal serum albumin (4.3 g/dL), serum creatinine (1.0 mg/dL), estimated glomerular filtration rate (eGFR 94 mL/min/1.73 m²), and spot urinary protein-to-creatinine ratio within the reference range. Renal ultrasonography demonstrated bilaterally normal kidneys without calculi, scarring, or hydronephrosis. Table 1 summarizes the key laboratory findings at admission. Based on these findings, type 1 dRTA was considered the likely cause of her profound hypokalemia, leading to a HPP episode.

Table 1.

Laboratory Investigations on Admission.

Parameter	Measured Value	Reference Range	Interpretation
Serum Potassium	1.4 mEq/L	3.5–5.0 mEq/L	Critically low; consistent with paralysis
Serum Bicarbonate	13 mEq/L	22–26 mEq/L	Metabolic acidosis
Arterial pH	7.26	7.35–7.45	Acidemia
Anion Gap	12	8–16	Normal; suggests non-anion gap acidosis
Serum Creatinine	1.0 mg/dL	0.6–1.2 mg/dL	Normal renal function
Serum Albumin	4.3 g/dL	3.5–5.5 g/dL	Normal
Urine pH	7.6	<5.5 in dRTA	Inappropriately alkaline
Urinary Potassium	20 mEq/L	Variable	Suggestive of renal potassium loss
Urinary Anion Gap	18	Negative or near-zero	Indicates impaired NH4+ excretion

Laboratory results upon the patient’s admission, indicating hypokalemia, metabolic acidosis with a near-normal anion gap, and renal losses of potassium in a setting consistent with Type 1 distal RTA.

She received parenteral potassium chloride at a dose of 20 mEq in 100 mL of intravenous fluid, which was repeated until serum potassium values began to normalize. This correction was achieved over 2 days. She also required intravenous sodium bicarbonate at a dose of 125 mEq over 4 hours, followed by 125 mEq over the subsequent 24 hours to address her metabolic acidosis. The coexistence of autoimmunity was managed through intravenous methylprednisolone at 500 mg/day for 3 consecutive days, then conversion to oral prednisolone at 40 mg/day, tapered across 2 months. Oral pilocarpine at 5 mg every 8 hours was prescribed to mitigate dryness symptoms related to Sjögren’s syndrome. Table 2 presents the primary treatments administered and their duration. After 2 days of therapy, her limb strength began to recover, and follow-up blood tests showed improved potassium and bicarbonate levels. A comparison of key biochemical values before and after treatment is presented in Table 3.

Table 2.

Administered Therapeutic Regimen and Duration.

Treatment	Dosage and route	Duration	Therapeutic goal
Potassium Chloride (IV)	20 mEq in 100 mL, repeated	48 hours	Correct severe hypokalemia
Sodium Bicarbonate (IV)	125 mEq over 4 h, then 125 mEq/24 h	2 days	Correct metabolic acidosis
Methylprednisolone (IV)	500 mg/day	3 days	Immunosuppressive induction for pSS
Prednisolone (Oral)	40 mg/day, tapering	2 months	Maintenance immune modulation
Pilocarpine (Oral)	5 mg every 8 h	Ongoing	Manage xerostomia and xerophthalmia
Potassium Citrate (Oral)	15 mEq twice daily	Maintenance	Alkali replacement and urinary buffering
Potassium Chloride (Oral)	15 mL thrice daily	15 days	Oral potassium support

Table 3.

Comparison of pre- and post-treatment biochemical parameters.

Parameter	Admission	Day 3 Post-treatment	Reference range
Serum Potassium	1.4 mEq/L	4.2 mEq/L	3.5–5.0 mEq/L
Serum Bicarbonate	13 mEq/L	23 mEq/L	22–26 mEq/L
Arterial pH	7.26	7.38	7.35–7.45
Urine pH	7.6	6.1	<5.5 in dRTA
Urinary Anion Gap	18	5	Negative/near-zero

The table documents improvements in serum potassium, bicarbonate levels, urinary pH, and urinary anion gap, affirming correction of acidosis and renal potassium handling.

Outline of the principal pharmacological interventions with specified dosages, routes, and treatment intervals. Intravenous correction was critical during the acute phase, followed by oral maintenance therapies and immunomodulation aimed at controlling pSS.

She was discharged on a regimen of tapering oral steroids, pilocarpine (5 mg 3 times a day), potassium citrate (15 mEq twice daily), and potassium chloride syrup (15 mL thrice daily diluted in half a glass of water) for 15 days. At a six-month follow-up appointment, the patient reported no additional episodes of weakness, and her laboratory results remained within normal limits.

Discussion

This case demonstrates a rare but clinically significant scenario in which pSS triggers autoimmune-mediated dRTA, leading to severe hypokalemia and HPP. This condition can arise from both inherited and acquired disorders of potassium homeostasis. ¹⁰ When distal RTA is involved, metabolic acidosis is accompanied by urinary potassium loss, leading to a precipitous decline in serum potassium that disrupts neuromuscular conduction. ¹¹ Type 1 RTA involves a defect in the ability of intercalated cells in the distal nephron to secrete hydrogen ions, often related to impaired function of H-ATPases or associated transporter channels.^12,13 The resulting inability to acidify urine below a pH of 5.5 sets the stage for systemic acidosis and potassium depletion. ¹⁴

The diagnosis of RTA, particularly in adults, is not routinely encountered in clinical practice and requires exclusion of more common renal-affecting pathologies. ¹⁵ In this patient, potential differentials such as diabetes mellitus, hypertension, nephrolithiasis, chronic kidney disease, alcohol abuse, oral contraceptive use, and excessive calcium or vitamin C supplementation were all systematically ruled out based on clinical history and biochemical profiling. Furthermore, standard investigations, including serum creatinine, albumin, eGFR, spot urine protein-to-creatinine ratio, and renal ultrasonography, were performed to rule out glomerular and structural causes of acidosis or potassium loss. Renal ultrasonography revealed no nephrolithiasis or parenchymal scarring. These steps conform to the accepted nephrological practice, where dRTA remains a diagnosis of exclusion after structural, glomerular, and endocrine causes are systematically cleared.

Exocrine glands are frequently affected in pSS and may also alter renal physiology. Some patients have high titers of autoantibodies, including those directed against carbonic anhydrase, compromising acid-handling mechanisms. ¹⁶ Existing literature suggests that a subset of individuals with pSS develop clinically significant distal RTA, and a fraction of these patients experience acute muscle weakness or paralysis.^{17 –19}

What makes this case unique is that the patient had no prior diagnosis of Sjögren’s syndrome or any systemic autoimmune condition. She presented with flaccid quadriplegia due to severe hypokalemia in the absence of a prior paralytic episode or known renal pathology, making the case diagnostically challenging. Moreover, this case reinforces the critical need to interpret urine pH, urinary anion gap, and acid-base status in combination, especially when the initial renal function appears to be preserved. Targeted autoimmune screening in a patient with chronic sicca symptoms led to the identification of a systemic autoimmune condition, confirming the link between immunologic injury and tubular dysfunction. Such diagnostic insights may otherwise be missed in the absence of overt extrarenal features.

Unlike many reported cases in which renal involvement followed an established Sjögren’s diagnosis,^{20 –23} this report presents a rare case of HPP as the initial clinical manifestation, which prompted a retrospective diagnosis of pSS. The need for prompt recognition is evident in these clinical scenarios because severe hypokalemia can lead to respiratory failure or rhabdomyolysis if uncorrected. ²⁴ Although the present patient had no prior episodes of paralysis, her extensive autoimmune background likely triggered an abrupt renal tubular defect that emerged when serum potassium levels reached a critically low point. Intervention requires vigilant electrolyte correction, especially careful potassium supplementation, to prevent rebound hyperkalemia once the episode resolves. ²⁵ Concomitant alkalinization with sodium bicarbonate administration is warranted in cases of profound metabolic acidosis, and the potential for rebound metabolic disturbances should be monitored.^26,27 Immune modulation is equally pivotal if an underlying autoimmune disease is found to contribute to or drive pathogenesis, as was the case with Sjögren’s syndrome in this patient. Approaches to therapy also encompass symptomatic management of dryness using agents, such as pilocarpine, and disease control with steroids.

This case thereby contributes a strong educational value: it emphasizes the importance of a detailed history (e.g., sicca symptoms), judicious autoimmune work-up, and awareness of rare presentations of pSS in acute care settings. For both rheumatologists and emergency physicians, it expands the clinical index of suspicion for diagnosing the secondary causes of HPP and presents a logical, algorithmic diagnostic flow.

Conclusion

Although rare, HPP can be life threatening without timely clinical recognition and management. Secondary etiologies, such as distal RTA, must be thoroughly explored, especially when new-onset episodes of profound muscle weakness occur in the absence of familial or endocrine causes. In this case, the patient benefited from aggressive potassium repletion, meticulous control of acid-base status, and immunosuppressive therapy targeting the underlying pSS. A structured diagnostic approach that includes the exclusion of glomerular, structural, and systemic causes, followed by appropriate autoimmune screening, is essential for accurate classification and targeted intervention. Early detection is essential to avert catastrophic complications, and a comprehensive approach that addresses both electrolyte derangements and autoimmune activity has the greatest potential for restoring neurological function and preventing recurrence.