A Challenging Diagnosis of IgG4-Related Disease When Understanding Limitations of Laboratory Testing Was Pivotal.

A 76-year-old man was incidentally found on a CT scan to have lymphadenopathy and bilateral kidney enlargement suggestive of infiltrative renal disease. He was largely asymptomatic but had bilateral salivary and lacrimal gland enlargement. A grossly elevated serum IgG (>70 g/L) with concomitant suppression of other immunoglobulins, a small IgG restriction, and a parotid biopsy revealing lymphoplasmacytic infiltrate with slight kappa light chain excess all suggested a lymphoproliferative disorder (LPD). The diagnostic workup was further confounded by a normal serum IgG4 concentration. Moreover, bone marrow and renal biopsies did not reveal evidence of LPD. Discussion with the laboratory not only clarified that the markedly increased total IgG could not be accounted for by the small IgG restriction, but also identified a discrepancy in the IgG4 measurement. Repeat analysis of a follow-up sample revealed an elevated IgG4 of 5.94 (reference interval: 0.039-0.864) g/L, which prompted a repeat parotid biopsy that showed predominant IgG4+ lymphocytic infiltrates. Despite the deluding presentations, a final diagnosis of IgG4-related disease (IgG4-RD) was made based on elevated serum IgG4 concentrations and histopathological findings. This case highlights the importance of recognizing limitations of laboratory testing and the benefit of close communications among clinical subspecialties and the laboratory.

Incidence of skeletal morbidity rates over time in patients with multiple myeloma-related bone disease as reported in randomized trials employing bone-modifying agents.

AIM: The purpose of this review was to investigate if advances in bone-targeted therapies have decreased the incidence of skeletal morbidity rates over time in patients with multiple myeloma-related bone disease. METHODS: A literature search was conducted over the OvidSP platform in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify Phase III results from bone-targeted therapy trials in patients with multiple myeloma. The skeletal morbidity rate was the end point of interest, and for each study, a mean year of enrollment ([start of enrollment + end of enrollment]/2) was calculated. RESULTS: A total of eight study arms were identified, with only two placebo arms; therefore, a weighted linear regression was not feasible and only intervention treatment arms were analyzed. A statistically significant downward trend in the skeletal morbidity rate was observed in all intervention arms. CONCLUSION: The incidence of skeletal morbidity rates has decreased significantly over time in patients with multiple myeloma.