ARTHRITIS & RHEUMATISM Volume 36 Number 12, December 1993, pp 1735-1738 0 1993, American College of Rheurnatology 1735 SJOGREN’S SYNDROME PRESENTING AS HYPOKALEMIC PERIODIC PARALYSIS JAMES E. DOWD and PETER E. LIPSKY We describe a 21-year-old Hispanic woman who presented with hypokalemic paralysis as the initial manifestation of Sjogren’s syndrome (SS). Our review of the English literature revealed 12 previously reported cases of SS and renal tubular acidosis (RTA). Paralysis often preceded the sicca complex in those patients. Renal function in the patients with hypokalemic paralysis was reduced compared with that in patients who had primary SS and RTA but no history of hypokalemic paralysis (P< 0.002). Hypokalemic periodic paralysis is a rare manifestation of SS. It is seen more often in patients with primary SS, may precede the classic sicca complex, and may serve as a clinical marker for more severe renal disease in patients who have primary SS and RTA. The periodic paralyses are a heterogeneous group of disorders in which an acute onset of weakness is associated with abnormalities in serum potassium levels (1). Hyperkalemic periodic paralysis, which may be associated with elevated or normal serum potassium levels, has recently been linked to a sodium-channel gene on chromosome 17 (2). Hypokalemic periodic paralysis and thyrotoxic periodic paralysis are usually associated with a decrease in total body and serum levels of potassium, respecFrom the Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas. Supported in part by an NIH Institutional Training Grant. James E. Dowd, MD; Peter E. Lipsky, MD. Address reprint requests to James E. Dowd, MD, Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-8844. Submitted for publication March 15, 1993; accepted in revised form June 8, 1993. tively. Genetic linkages have yet to be defined, but dominant inheritance is common. Hypokalemic periodic paralysis has also been described in patients with potassium-wasting renal tubular acidosis (RTA) (3). We report here a case of hypokalemic periodic paralysis as the presenting symptom of primary Sjogren’s syndrome (SS). CASE REPORT A 21-year-old Latin American woman residing in the United States, presented in March 1992 with a 2-day history of progressive weakness and myalgias that began in her lower extremities. Twenty-four hours before admission, the patient developed nausea, vomiting, and quadriparesis. A similar episode had occurred 1 month previously, and she was evaluated locally. Laboratory values at that time were K 2.3 mEq/liter, Na 133 mEqAiter, C1 104 mEq/liter, C 0 2 18 mEq/liter, hemoglobin 9.8 g d d l , and hematocrit 24.0%, and normal thyroid function. The patient traveled to Mexico for therapy, and was given 2 anthelmintics, an anxiolytic, multivitamins with iron, and oral potassium. The weakness improved with these medications and with oral hydration. She had no other episodes of weakness until the current illness. The patient had no history of fever, chills, rash, abdominal pain, diarrhea, tenesmus, dysuria, polyuria, laxative or diuretic use, pica, or toluene ingestion. Review of systems revealed periodic painless swelling of the angle of her jaw over the previous 3 years, most recently, 8 months prior to admission. These episodes were accompanied by dry mouth and thirst, but no dryness of the eyes. 1736 Examination on admission to the hospital revealed a thin and alert woman of normal body habitus, with a recumbent blood pressure and pulse of 100/65 mm Hg and 76 beats per minute and assisted sitting blood pressure and pulse of 88/palpable and 85, respectively. Her temperature was 36.8"C orally and respiratory rate was 18 per minute. Her sclera were anicteric, and conjunctiva noninjected. Fundi were normal. She had a bulging, nonerythematous left tympanic membrane. There was firm, nontender swelling over both parotids. Her oropharynx was dry, with glossitis. There was no cervical, axillary , or inguinal lymphadenopathy. Her thyroid was normal. Her chest was clear. There was a II/VI systolic ejection murmur at the left lower sternal border, without radiation. Her abdomen was soft and nontender, without hepatosplenomegaly or costovertebral angle tenderness. Her skin was dry, but otherwise normal. There was no joint or soft tissue swelling, tenderness, or deformity. Neurologic examination revealed grade 3/5 weakness of the proximal muscles and grade 4/5 weakness distally. She was unable to stand or walk. Examination of the cranial nerves, reflexes, and sensory status gave normal results. Laboratory examination revealed the following values: Na 136 mEqfliter (normal 137-145), C1 110 mEqfliter (normal 101-1 1 l), K 1.6 mEqfliter (normal 3.6-5.0),HCO, 9 mEqfliter (normal 22-31), anion gap +7 (normal <12), blood urea nitrogen 12 mgidl (normal 7-21), serum creatinine 1.1 mg/dl (normal 0.7-1.5), Mg 2.2 mEq/liter (normal 1.4-1.8), Ca 9.2 mgidl (normal 9.1-10.6),PO4 2.6 mg/dl (normal 2.5-4.5),creatine kinase 88 unitdliter (normal 35-230), and total protein 10.1 gmldl (normal 6.3-8.2).The serum white blood cell (WBC) count was 18,300/mm3, the hemoglobin level was 10.6 gm/dl (normal 12.0-15.2), the platelet count was 214,000/mm3(normal 140,000-450,000), and the erythrocyte sedimentation rate was 74 mmhour (normal 0-15). Analysis of blood gases showed the following levels: pH 7.36 (normal 7.34-7.44), Pco, 30 mm Hg (normal 35-45), Po, 108 mm Hg (normal 75-loo), and HCO, 17 mEq/liter (normal 22-26). Urinalysis showed a pH value of 7.0,specific gravity of 1.010,a trace of protein, 3-5 WBC per high power field, Na value of 38 mEq/liter, K of 15 mEq/liter, CI of 39 mEqAiter, urinary anion gap of +14, and urinary osmolality of 133 (normal 301-896). An initial diagnosis of hypokalemic periodic paralysis with a non-anion gap acidosis was made. The patient was begun on volume replacement and a DOWD AND LIPSKY regimen of combination oral and intravenous potassium. The presence of a positive urinary anion gap and a high urinary pH despite hyperchloremic acidosis was consistent with distal renal tubular acidosis. Subsequently, oral citrate solution was administered to compensate for the renal tubular acidification defect. The patient began to regain her strength within 24 hours of initiation of therapy. Approximately 1,500 mEq of supplemental potassium was administered in the first 3 days of hospitalization. The history of dry mouth and periodic parotid swelling confirmed by examination suggested SS as the etiology of the RTA. A Schirmer's test on hospital day 2 demonstrated 2 mm of tear flow at 5 minutes (normal 215 mm). Biopsy of the minor salivary glands of the lip showed >2 foci of lymphocytes/4 mm2 (Greenspan scale), indicative of Sjogren's syndrome. Antinuclear antibodies were present at a titer of 1540, in a speckled pattern, rheumatoid factor was 497 IU/ml by nephelometry (normal <30), and anti-Ro/SS-A antibodies were present, confirming the pathologic diagnosis. The elevated total protein level was further evaluated by serum protein electrophoresis, which revealed a polyclonal gammopathy. The ferritin (10 ngiml) and serum iron (26 pg/dl) levels were consistent with iron deficiency anemia. By hospital day 3, the patient was able to walk without assistance, and her muscle strength was normal. The discharge diagnoses were SS and distal RTA causing hypokalemic periodic paralysis. At 4 months of followup, the patient reported dry mouth, but had no symptoms of dryness of the eyes or further weakness. Laboratory values at that time were sodium 139 mEq/liter, potassium 3.5mEq/liter, chloride 102 mEq/ liter, bicarbonate 23 mEq/liter, and creatinine 1.O mg/dl. Oral potassium and citrate were continued. DISCUSSION This case represents 1 of only 3 cases reported from the United States and 10 other cases in the English literature. Although our patient was Spanish speaking and born in Mexico, her name is Germanic, suggesting other European genetic influences. This differs from the Asian bias suggested by the country of origin in 9 of the other 12 reported cases (Table 1). A similar Asian bias has been reported in patients with thyrotoxic hypokalemic periodic paralysis (1).Tissue typing of these patients (Table 1) was not available for comparison. Our patient met all 4 of the proposed criteria for PRIMARY SS AND HYPOKALEMIC PERIODIC PARALYSIS 1737 Table 1. Hypokalemic periodic paralysis as the predominant manifestation of Sjogren’s syndrome* Case number Agelsex Race Other signs and symptoms Potassium(mEq1liter) Urine PH Protein Creatinine clearance (mllminute) ESR Polyclonal gammopathy Diagnostic Sch./Sial. Anti-Rolanti-La RFIANA Biopsy Reference Index case 1 2 21lF LAm Sicca 3QlF Jpn - 38lF Fr RA, HB 1.6 1.5 1.4 1.2 1.7 2.4 1.0 7.0 trace NA 7.5 NA 68 7.5 3+ 52 NA NA NA NA NA NA NA NA NA 7.5 74 NA NA 73 48 88 NA + N A +/NA +I+I+ Lip -I+ +/NA + - + 3 4 5 34lF 32lF 36lF Ch Ch Ch - + 6 63lF Swed Sicca 7 6.5 2+ NA NA NA + 7.5 - NA NA NA +/NANA/+ NA/+ +I+ +/NA +/NA +I+ +I+ +I+ -I-,ENA NA NA +I+ NA +I+ +I+ +/+ NA Lip Lip, renal Lip Renal Lip NA Renal Lip 11 12 13 13 13 14 8 15 +I-I+I+ +I-,ACA 9 10 11 12 34lF 30lF 14lF 41lF 54lF 36lF Fil NA JPn Jpn Jpn Jpn NC Sclero- Leg pain, RP, RP Arthral. derma growth retard. arthral. 2.3 2.8 2.5 2.3 2.6 2.1 1+ NA + 8 7.0 1 +/AA 70 7.0 1+ 62 6.9 I+ 54 6.6 1+ 38 27 49 32 10 - -/NA NA +/+ Lac., par. 7 +/NA NA +I+ Lac., par. 7 + + + +/NA +/NA NA NA +I-IRenal Lac., par. 7 7 * LAm = Latin American; Jpn = Japanese; Fr = French; Ch = southern Chinese; Swed = Swedish; Fil = Filipino; NA = not available; RA = respiratory arrest; HB = heart block; NC = nephrocalcinosis; growth retard. = growth retardation; RP = Raynaud’s phenomenon; arthral. = arthralgias; AA = amino acids; ESR = erythrocyte sedimentation rate; Sch.lSia1. = Schirmer’s testkadionuclide sialography; ENA = extractable nuclear antigen: RFIANA = rheumatoid factorlantinuclear antibody; ACA = anticentromere antibody; Lac. = lacrimal gland; par. = parotid gland. the diagnosis of SS (4). Moreover, her young age, sex, early extraglandular involvement in the form of RTA, and the presence of ROBS-A antibodies were consistent with the primary SS phenotype (5). Hypokalemic periodic paralysis was the presenting manifestation of primary SS in this patient, preceding symptoms of xerostomia and xerophthalmia. Review of the other reported cases appeared to corroborate this observation, with quadriparesis preceding arthrlagias, Raynaud’s phenomenon, sicca symptoms, and symptomatic urinary calcinosis. In cases 6, 8, 9, and 12 the “other symptoms” preceded or accompanied quadriparesis. Compared with the patients studied by Pavlidas, Siamopolous, and colleagues (5,6), this subset of patients with primary SS (Table I) appeared to seek medical attention earlier in the course of disease and at a younger average age (36 versus 52 and 50 years, respectively). Renal involvement (symptomatic and asymptomatic) has been estimated to occur in 3040% of SS patients (6). SS patients may have clinical and pathologic evidence of both proximal and distal types of RTA (7,8). Our patient exhibited no evidence of proximal RTA, but only distal abnormalities that may have related to her marked hypergammaglobulinemia. The clinical severity of RTA in this group (Table 1) may be a reflection of more extensive renal pathology, as suggested by their lower average creatinine clearance rate than in patients with primary SS and RTA, but without hypokalemic paralysis (57 12 muminute versus 83 2 9 ml/minute; P < 0.002) (6). It should be emphasized that our patient had a normal serum creatinine value when she first presented and has not exhibited renal failure over the ensuing 2 years of followup. Therefore, renal failure, as opposed to tubular dysfunction, may not be a part of this syndrome. Renal biopsies in these patients (Table 1) usually showed evidence of interstitial nephritis, with lymphocytic and plasma cell infiltration and tubular atrophy. Similar pathology has been described in patients with SS and renal tubular acidosis without hypokalemic periodic paralysis (5). Our patient’s history of only 1 previous episode of paresis, the lack of intercurrent or chronic weakness, the normal serum creatine kinase value, and her rapid response to therapy with full recovery of strength precluded the need for electromyography andlor muscle biopsy for diagnosis. Some patients with SS may develop an inflammatory myopathy resembling polymyositis or dermatomyositis; moreover, * 1738 a noninflammatory myopathy with pathologic changes consisting of microcysts, resembling large lipocytes within the muscle fascicles, has been described in SS (9). It is unlikely that our patient had a primary myopathic process, although chronic or recurrent hypokalemia may lead to vacuolar degeneration of myofibrils (1). The use of the urinary anion gap (Na + K - C1) as a measure of urinary ammonium excretion during acidosis may obviate the need to perform acid load or bicarbonate excretion tests to confirm RTA (10). In our patient, the urinary anion gap was utilized on admission to determine the cause of hyperchloremic metabolic acidosis. Our patient had a positive urinary anion gap in the presence of acidemia, which suggested an inability to excrete excess acid, a feature consistent with distal RTA. A negative urinary anion gap in the presence of hyperchloremic acidosis may be normal or may suggest a gastrointestinal loss of potassium such as occurs with diarrhea. The presence of hypokalemia and an inappropriately high urine pH, as in our patient, or urinary calcinosis may further confirm the diagnosis of distal RTA. As this case and others like it demonstrate, hypokalemic periodic paralysis as the initial manifestation of primary SS is rare, but when it occurs, it may precede symptoms of xerostomia and xerophthalmia. This presentation may also serve as a clinical marker of more severe renal disease in patients with primary SS and RTA. The diagnosis of primary SS should be considered in premenopausal women, especially those of Asian origin, but in other racial groups as well, who present with rapidly progressive weakness and hypokalemia, with or without the sicca complex. Calculation of the urinary anion gap may be utilized during an acute episode of hyperchloremic metabolic acidosis to quickly confirm the diagnosis of distal RTA. Acute therapy with potassium and alkali replacement must DOWD AND LIPSKY be tailored to the individual patient based on serum chemistries. Long-term followup should monitor electrolytes and renal function as well as clinical disease. REFERENCES 1 . Engel AG: Periodic paralysis, Myology. Edited by AG Engel and BQ Banker. New York, McGraw-Hill, 1986 2. Ptacek LJ, George AL Jr., Griggs RC, Tawil R, Kallen RG, Barchi RL, Robertson M, Leppert MF: Identification of a mutation in the gene causing hyperkalemic periodic paralysis. Cell 67:1021-1027, 1991 3. Owen EE, Verner JV: Renal tubular disease with muscle paralysis and hypokalemia. Am J Med 28%-21, 1960 4. Fox RI, Robinson CA, Curd JG, Kozin F, Howell FV: Sjogren’s syndrome: proposed criteria for classification. Arthritis Rheum 29:577-585, 1986 5. Pavlidis NA, Karch S, Moutsopoulos HM: The clinical picture of primary Sjogren’s syndrome: a retrospective study. J Rheumatol9:658-690, 1982 6. Siamopoulos KC, Elisaf M, Drosos AA, Mavridis AA, Moutsopoulos HM: Renal tubular acidosis in primary Sjogren’s syndrome. Clin Rheumatol 11:226-230, 1992 7. Shioji R, Furayama T, Onodera S, Saito H, Ito H, Sasaki Y: Sjogren’s syndrome and renal tubular acidosis. Am J Med 48:456-463, 1970 8. Glassock RJ, Feinstein EI, Tanner R, Blau R, Koss M: Metabolic acidosis in a young woman. Am J Med 4:58-65, 1984 9. Denko CW, Old SW: Myopathy in the sicca syndrome. Am J Clin Pathol 51:631-637, 1969 10. Battle DC, Hizon M, Cohen E, Gutterman C, Gupta R: The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis. N Engl J Med 318594599, 1988 11. Hattori N, Hino M, Ishihara T, Moridera K, Ikekubo K, Kurahachi H: Hypokalemic paralysis associated with distal renal tubular acidosis. Intern Med 31:662-665, 1992 12. Poux JM, Peyronnet P, Le Meur Y, Favereau JP, Charmes JP, Leroux-Robert C: Hypokalemic quadriplegia and respiratory arrest revealing primary Sjogren’s syndrome. Clin Nephrol 37:18S191, 1992 13. Pun KK, Wong CK, Tsui EYL, Tam SCF, Kung AWC, Wang CCL: Hypokalemic periodic paralysis due to Sjogren’s syndrome in Chinese patients. Ann Intern Med 110:405-406, 1989 14. Christensen KS: Hypokalemic paralysis in Sjogren’s syndrome secondary to renal tubular acidosis. Scand J Rheumatol 14:5860, 1985 15. Raskin RJ, Tesar JT, Lawless OJ: Hypokalemic periodic paralysis in Sjogren’s syndrome. Arch Intern Med 141:1671-1673, 1981
1/--страниц