An Atypical Etiology of Quadriparesis: A Diagnostic Challenge

Introduction

Quadriparesis is a medical emergency with a broad differential diagnosis ranging from neurological to metabolic causes. Acute flaccid paralysis often prompts initial consideration of Guillain-Barré syndrome, transverse myelitis, or myopathies. However, metabolic disorders such as hypokalemic paralysis should not be overlooked, especially when accompanied by characteristic biochemical findings. Renal tubular acidosis (RTA), though rare, is a recognized cause of hypokalemic paralysis. In adults, autoimmune diseases, most notably primary Sjögren’s syndrome, are the leading cause of acquired distal renal tubular acidosis (dRTA). Although Sjögren’s syndrome typically presents with sicca symptoms, it may occasionally manifest with isolated renal involvement, delaying diagnosis.

We present two cases of young women with progressive quadriparesis due to severe hypokalemia, ultimately diagnosed with dRTA secondary to primary Sjögren’s syndrome. These cases highlight the diagnostic challenges in atypical presentations and underscore the importance of a high index of suspicion for autoimmune etiologies in metabolic paralysis. Early recognition and immunosuppressive treatment can significantly improve outcomes in such patients.

Case Report

Our first case was a 34-year-old lady who presented to the emergency department with a history of progressive quadriparesis over one week. There was no history of swallowing difficulty, slurred speech, respiratory distress, or sphincter involvement. She denied gastrointestinal symptoms such as loose motion, vomiting, or dyspepsia. On physical examination, she was alert and reactive. Her blood pressure was 120/80 mmHg and her oxygen saturation was 97% on room air. Chest and abdominal examinations were noncontributory. Deep tendon reflexes were absent, and strength was 3/5 in all four limbs, more marked in the proximal muscles. No Babinski response was found. The differential diagnosis for acute flaccid paralysis such as Guillain‑Barre syndrome and hypokalemic paralysis was considered. Results of relevant laboratory investigations are shown in Table 1. She had profound hypokalemia with normal anion gap metabolic acidosis, suggestive of distal RTA. Further evaluation revealed the presence of underlying Sjögren’s syndrome and, subsequently, hypothyroidism due to underlying Hashimoto thyroiditis.

Table 1. Laboratory investigations

ESR: Erythrocyte sedimentation rate ,K: potassium , Ca: calcium, USG: Ultrasound sonography, ANA: Antinuclear antibodies, FT4 : free T4, TSH: thyroid stimulating hormone, Ab : antibody

The second patient was a 28-year-old woman who presented with acute onset of quadriparesis of four days’ duration. She reported a similar episode four months earlier, which had resolved with medical treatment.

Neurological examination revealed quadriparesis with muscle strength graded as 3/5 in all four limbs, preserved sensation, and diminished deep tendon reflexes. Her laboratory results are presented in Table 2. She was found to have severe hypokalemia, normal anion gap metabolic acidosis, and an alkaline urinary pH—findings consistent with distal renal tubular acidosis (dRTA).

On further questioning, she reported symptoms of dry mouth and eye irritation over the past six months. There were no clinical features suggestive of other connective tissue diseases. Autoimmune evaluation confirmed a diagnosis of primary Sjögren’s syndrome.

Table 2. Laboratory investigations

ESR: Erythrocyte sedimentation rate ,K: potassium , Ca: calcium, USG: Ultrasound sonography, ANA: Antinuclear antibodies, FT4 : free T4, TSH: thyroid stimulating hormone,

The patients were ultimately diagnosed with distal RTA. Intravenous potassium infusion and sodium bicarbonate were initiated, leading to clinical improvement. Investigations to rule out underlying associated connective tissue diseases were conducted and found to be strongly positive for both SS-A and SS-B antibodies in both cases; other antibodies were negative. A joint consultation was held with the Rheumatology Department. Patients were commenced on methylprednisolone, methotrexate, hydroxychloroquine, oral sodium bicarbonate, and oral potassium supplementation and were subsequently discharged in stable condition.

Hypokalemic paralysis is a rare condition characterized by episodic muscle weakness in the setting of hypokalemia. Although various disorders have been associated with this condition, renal tubular acidosis (RTA) should also be considered in the presence of metabolic acidosis with a normal anion gap. RTA is typically suspected when hyperchloremic metabolic acidosis (HMA) is present and is classified into three types: proximal RTA, distal RTA (dRTA), and hyperkalemic RTA. Distal RTA is marked by an impaired ability to excrete acid and disturbances in potassium homeostasis. Primary Sjögren’s syndrome (pSS), an autoimmune disorder primarily affecting the exocrine glands, may also lead to renal involvement through both tubular and glomerular damage. In adults, pSS is recognized as the most common cause of acquired dRTA. The significance of these cases lies in their unusual clinical presentation, where severe symptomatic hypokalemia was the initial manifestation of underlying pSS.

Discussion

Hypokalemic paralysis is a rare neuromuscular disorder characterized by episodes of muscle weakness or paralysis associated with low potassium levels. It can be primary (genetic) or secondary to other medical conditions. Secondary forms are more common and are the result of acquired hypokalemia such as thyrotoxicosis, hyperaldosteronism, diabetic ketoacidosis, diarrhea, vomiting, drugs, or RTA ¹.

The term RTA applies to a group of disorders characterized by normal anion gap (hyperchloremic) metabolic acidosis due to impaired renal acid-base regulation. Unlike metabolic acidosis caused by decreased glomerular filtration, RTA arises from defects in tubular bicarbonate reabsorption, hydrogen ion secretion, or both, despite relatively preserved glomerular function ².

dRTA is a relatively rare condition in which the distal tubules of the kidney fail to adequately secrete hydrogen ions, leading to an inability to acidify the urine below a pH of 5.5. Its prevalence is not well established, but it is more commonly reported in association with autoimmune disorders ³. In India, Rao et al. ⁴ reported 31 cases of hypokalemic paralysis, out of which Sjögren’s syndrome was found to be the etiology in three cases. Studies have shown that up to 25–33% of patients with primary Sjögren’s syndrome may develop some form of RTA, and it is more likely to be associated when there is positive Anti-Ro and La antibodies, longer disease duration, xerostomia, hypertension, and higher creatinine and proteinuria ⁵.

Sjögren’s syndrome is an autoimmune condition that typically involves lymphocytic infiltration of the salivary, parotid, and lacrimal glands, resulting in the characteristic symptoms of xerosis (dry eyes) and xerostomia (dry mouth). Although Sjögren’s syndrome is often characterized by sicca symptoms, they are not always present. A case series by Shioji et al. ⁶ described four cases of Sjögren’s syndrome complicated by RTA, in which three of the four patients presented with arthralgia or muscle weakness. Only two reported dry mouth, and none reported any ocular abnormality ⁶. A number of case reports have also reported muscle weakness, pathological fractures, and hypokalemic paralysis as the presenting symptoms of Sjögren’s syndrome secondary to distal RTA. Therefore, symptoms related to RTA, even in the absence of sicca symptoms, may be a clue that triggers the discovery of Sjögren’s syndrome. Hypokalemic paralysis as the first manifestation of distal RTA due to Sjögren’s syndrome is uncommon yet ⁷. It is worth noting that Sjögren’s syndrome should be considered even in the absence of sicca symptoms, as in our first case.

Approximately one‑third of patients with Sjögren’s syndrome present with systemic manifestations. The spectrum of renal disease includes interstitial nephritis, which can manifest as distal RTA, proximal RTA, tubular proteinuria, nephrogenic diabetes insipidus, glomerular diseases, or renal failure ^8,9.

Autoimmune thyroid disease (AITD) is significantly more common in patients with Sjögren’s syndrome (SS) than in the general population. A study of 525 SS patients found that 31.8% had AITD. In a survey by the Sjögren’s Foundation, 23% of respondents reported having both AITD and Sjögren’s. Ara et al, in a cohort of 160 primary SS patients, found evidence of thyroid disease in 36% of patients: 20% were diagnosed with AITD and 16% were diagnosed with non-AITD. ¹⁰

A combination of corticosteroids and other immunosuppressive drugs has been reported to slow the progression of renal damage in Sjögren’s syndrome. Agents that are commonly used include hydroxychloroquine, prednisone, methotrexate, mycophenolate sodium, azathioprine, and cyclosporine. A similar management strategy was approached in this very case, closely matching the standard or recommended guidelines needed to manage this type of case, with the addition of potassium supplementation ¹¹. It is recommended to treat dRTA with potassium citrate, which is an effective treatment for both the symptoms and complications of dRTA by restoring acid-base balance ¹². In accordance with KDIGO 2024 guidelines, alkali therapy such as sodium bicarbonate or potassium citrate is recommended for patients with tubular disorders by buffering excess hydrogen ions, thereby restoring systemic acid-base equilibrium. This intervention helps correct acid-base disturbances, mitigate bone demineralization, and prevent nephrolithiasis, thereby improving long-term renal outcomes ¹³.

Conclusion

Patients presenting with hypokalemic paralysis due to RTA should be worked up for underlying primary diseases such as Sjögren’s syndrome, even in the absence of classic symptoms.

This case emphasizes the need to consider a wide set of differential diagnoses, including Sjögren’s syndrome, in cases of unexplained renal tubular acidosis. Diagnosis at an early stage may allow for better control and prevent the progression of disease. Awareness of this rare condition should be maintained by healthcare professionals.

Learning Points

• Although Sjögren’s syndrome is characteristically associated with symptoms of dry eyes and mouth, extra-glandular renal manifestations are not uncommon presentations.
• The most common renal manifestation of Sjögren’s syndrome is tubulointerstitial nephritis, which can manifest as renal tubular acidosis.
• Individuals with seemingly idiopathic distal renal tubular acidosis should be screened for Sjögren’s syndrome.

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Author Information

Ni-Ni-Aung, May-Kyi-Oo, Min-Zaw-Oo

1. Junior consultant physician, Department of Medicine, Yangon General Hospital, Yangon
2. Senior Consultant physician, Department of Medicine, Yangon General Hospital, Yangon
3. Professor, Medical Unit (3), Department of Medicine, Yangon General Hospital, Yangon