Study Evaluates Anatomical Pathology of Gout

In a study recently published in BMC Musculoskeletal Disorders, researchers reviewed the anatomical pathology of tissues impacted in gout patients.

Gout, caused by inflammatory arthritis, affects almost 4% of the U.S. adult population, according to the study.

“The aim of this systematic literature review was to describe comprehensively the anatomical pathology of gout, including the macroscopic appearances, light microscopy (including immunohistochemistry) and electron microscopy,” the study authors wrote.

To conduct their review, the researchers queried PubMed, Excerpta, Medica Database, and Web of Science Core Collection using the following search terms: “gout or gouty,” “pathology or pathological or pathologies or histology or histological or histologies.” Articles describing microscopic or macroscopic tissue appearances of gout in human patients were included; articles not published in English or that only reported cytological analysis were excluded. There were no date restrictions, and the final search was conducted in March 2018.

#Gout is caused by deposition of uric acid crystals in the joint, causing inflammation.

— Arthritis Disorders (@ArthritisDisord) April 7, 2019

MSU Crystal Deposition and Tophus Dominate the Literature

The final analysis included a total of 417 articles; the most common articles detailed the anatomical pathology of gout in musculoskeletal structures, including bone, tendon and ligaments, synovium and cartilage; descriptions of skin and kidney pathology in gout patients were also common. Monosodium urate (MSU) crystal deposition and tophus were frequently discussed.

A total of 213 articles highlighted macroscopic appearances describing MSU crystal deposition; 325 reported light microscopic appearances, and only two articles discussed the electron microscopy. Out of the total 417 articles, only 15—fewer than 4%–did not report MSU crystal deposition.

The FDA has added a boxed warning to febuxostat cautioning that the gout drug may increase heart-related and all-cause mortality compared with allopurinol, a finding from a large postmarketing safety clinical trial conducted by the manufacturer https://t.co/oAuwh6vsSU

— JAMA (@JAMA_current) April 5, 2019

In macroscopic appearances, most MSU crystals were described as white; other descriptors included “sugar icing, chalky, snow-like, powdery, or toothpaste-like material,” the researchers noted. When discussing light microscopic appearances, “Rod or long needle shaped crystals were reported,” according to the researchers. Crystal collections varied in color, “including eosinophilic, basophilic, grayish, and colourless.”

Macroscopic appearances describing the tophus and light microscopic appearances were reported in 203 and 304 articles, respectively; 13 articles discussed immunohistochemistry, and five discussed electron microscopy appearances. Only seven of the total 417 articles—fewer than 2%–did not report tophi.

Regarding macroscopic appearances, “The tophus was described as a chalky while nodule, with variable size and shape of the tophus; irregular, nodular, plaque-like, cauliflower, fungiform, exophytic and multilobular lesions reported.” Descriptions of consistency varied and included “Firm, gritty, semi-solid, cheesy-like [and] gelatinous.”

Light microscopy of the tophus descriptions depicted an organized structure with a crystalline center “as an acellular (‘necrotic’) collection of MSU crystals.” A corona zone surrounded the crystalline center and was made up of multinucleated giant cells of the foreign body type, histiocytes, fibroblasts, lymphocytes and plasma cells. A fibrovascular zone surrounded the corona zone. Some tophi exhibited calcification.

Trivia question: How many people does gout affect every year?
Answer: Over three million. pic.twitter.com/wRiFqOEVUA

— Pain Evaluation & Management Center (@EvaluationPain) April 8, 2019

About 32% of articles described fixation methods, with most (n = 79) discussing formalin fixation, while 49 and five described ethanol fixation and other fixation methods, respectively.

“During a gout flare, diffuse acute neutrophilic synovial inflammation was evident,” the study authors wrote. “The tophus was described as an organised chronic giant cell granulomatous structure consisting of monosodium urate crystals, innate and adaptive immune cells, and fibrovascular tissue.”

The researchers concluded: “This analysis emphasizes the central role of MSU crystal deposition as the pathogenic lesion in gout, the typical patterns of involvement on anatomical pathology assessment that mirror the clinical presentation of disease, and the characteristic tissue response to deposited crystals.”