A 60-year-old woman comes to the office due to frequent urination. She gets up 3 times a night to urinate and drink water. She has also noticed some mild hoarseness, fatigue, and difficulty concentrating. Her eyes have been dry and "burning," for which she uses over-the-counter eye drops. The patient has no history of chronic medical conditions but has smoked a pack of cigarettes daily for 40 years.
Blood pressure is 144/78 mm Hg and pulse is 82/min and regular. Physical examination is unremarkable.
Laboratory results are as follows:
Which of the following is most likely to establish the diagnosis in this patient?

Question

A 60-year-old woman comes to the office due to frequent urination.  She gets up 3 times a night to urinate and drink water.  She has also noticed some mild hoarseness, fatigue, and difficulty concentrating.  Her eyes have been dry and "burning," for which she uses over-the-counter eye drops.  The patient has no history of chronic medical conditions but has smoked a pack of cigarettes daily for 40 years.
Blood pressure is 144/78 mm Hg and pulse is 82/min and regular.  Physical examination is unremarkable.
Laboratory results are as follows:
 Which of the following is most likely to establish the diagnosis in this patient?

Quizplus · Accepted Answer

11ec193a_9918_a80f_853d_256d0f6d88f3_MD0002_00 This patient with dry eyes, hoarseness, and fatigue has an elevated gamma globulin gap (total protein − albumin >4), raising suspicion for a chronic inflammatory disorder such as Sjögren syndrome (SS). SS is marked by lymphocytic infiltration of the lacrimal and salivary glands, which leads to the characteristic symptoms of dry eyes and dry mouth. Approximately 25% of cases are also accompanied by extraglandular disease of the skin, lungs, nervous system, heart, and/or kidneys. The most common renal manifestation of SS is chronic interstitial nephritis. Patients with this condition usually have mild renal insufficiency, a fairly benign urinalysis, and renal tubular abnormalities such as distal renal tubular acidosis (leading to metabolic acidosis with hypokalemia) and nephrogenic diabetes insipidus (leading to low urine osmolality, frequent urination, and excessive thirst). The diagnosis of SS relies on a combination of clinical, laboratory, and histologic findings. Patients with characteristic clinical findings, objective evidence of dry eyes/mouth, and strongly positive anti-SSA and anti-SSB antibody testing are generally considered to have the disorder. Those with weakly positive or absent anti-SSA and anti-SSB antibodies usually require lower lip salivary gland biopsy with histology. (Choice A) Chest CT scan with contrast could help diagnose sarcoidosis, which can cause an elevated gamma gap, dry eyes, and interstitial nephritis. However, most patients with sarcoidosis also have pulmonary, skin, and/or joint manifestations. (Choice C) Renal biopsy is typically required when a patient has an unclear cause of proteinuria, glomerulonephritis, or renal insufficiency. Although a renal biopsy in this patient would likely show interstitial nephritis, this finding would not be diagnostic of SS. Diagnosis must be established with anti-SSA and anti-SSB antibody testing and/or lip salivary gland biopsy. (Choice D) Urine and serum protein electrophoresis could help diagnose multiple myeloma, which can cause an elevated gamma gap, renal insufficiency with a bland urinalysis, and anemia. However, patients with multiple myeloma often also have bone pain and hypercalcemia. In addition, dry eyes and hoarseness would be uncommon symptoms. Hypergammaglobulinemia is common in many collagen vascular disorders and autoimmune diseases due to chronic inflammation. (Choice E) Chronic hepatitis C virus (HCV) can cause an SS-like syndrome and renal manifestations. However, HCV usually causes glomerular injury with a nephrotic (eg, large proteinuria) or nephritic (eg, hematuria, red cell casts) pattern on urinalysis. This patient has a bland urinalysis and no transaminitis, making HCV infection less likely. Educational objective: Sjögren syndrome (SS) is characterized by lymphocytic inflammation of the lacrimal and salivary glands, which leads to chronic dry eyes and dry mouth. Approximately 25% of patients have extraglandular manifestations in the skin, lungs, nervous system, heart, and/or kidneys (eg, chronic interstitial nephritis). Diagnosis usually requires anti-SSA and anti-SSB antibody testing and/or lower lip salivary gland biopsy. __________ References: Primary Sjögren's syndrome: new clinical and therapeutic concepts. (http://www.ncbi.nlm.nih.gov/pubmed/15498797) Clinically significant and biopsy-documented renal involvement in primary Sjögren's syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/10941353)

A 60-Year-Old Woman Comes to the Office Due to Frequent