Gout is not a rich man's disease. If affects men and women of all ages and social classes. The classic disease passes through four stages.
STAGE CHARACTERIZATION Asymptomatic hyperuricemia At puberty in males
Menopause in females
Acute gouty arthritis
Sudden onset of joint pain
Most are monoarticular with 50% occurring in 1st metatarsophalangeal joint
90% will develop symptoms in insteps, ankles, heels, knees, wrists, fingers, and elbows
Untreated may last for hours to weeks
Intercritical gout Asymptomatic period between acute attacks Chronic tophaceous gout Usually about 12 years from initial attack
Radiographs will show bone erosions and loss of joint space
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/
Other Diagnostic Testing
Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGIC ASSOCIATIONS CHARACTERIZATION Age Usually >30 years Genetic predisposition X-linked abnormalities of HGPRT
Primary gout is familial and multifactorial
Heavy alcohol consumption Predisposes to attacks Obesity Increases risk Certain drugs Thiazides Lead toxicity Increases tendency to develop saturnine gout
DISEASE ASSOCIATIONS CHARACTERIZATION Primary Gout 90% of cases Enzyme defects unknown Overproduction of uric acid
Normal excretion majority of cases
Increased excretion minority
Known enzyme defects Overproduction of uric acid
Seen in conditions such as partial HGPRT deficiency
Secondary Gout 10% of cases Associated with increased nuclei acid turnover such as leukemia Overproduction of uric acid with increased urinary excretion Chronic renal disease Reduced excretion of uric acid with normal production Inborn errors of metabolism Overproduction of uric acid with increased urinary excretion MUCORMYCOSIS
- Am J Dermatopathol. 2006 Aug;28(4):327-30 Abstract quote
Cutaneous zygomycosis is being increasingly recognized as a serious and life-threatening infection in debilitated and immunosuppressed patients, including transplant patients. The organisms are morphologically distinct but difficult to grow in cultures from clinical samples.
We report a case of cutaneous zygomycosis in a neonatal multi-visceral organ transplant patient, with subcutaneous panniculitis accompanied by extensive local acicular uric acid crystal deposition. Although the patient's serum uric acid was subsequently found to be in the normal range, transient hyperuricemia could not be excluded. Because we use a microwave-based processing system avoiding aqueous solutions, the crystals were maintained in the tissue sections and were shown by various methods to consist of monosodium urate. Early diagnosis combined with extensive debridement and prompt antifungal therapy resulted in a successful outcome.
We have coined the term "urate panniculitis" to describe this phenomenon.
PATHOGENESIS CHARACTERIZATION Uric acid is the end product of purine metabolism De novo pathway Purines are synthesized from nonpurine precursors Salvage pathway
Free purine bases are derived from the breakdown of nucleic acids of endogenous and exogenous origin and salvaged
HGPRT enzyme (hypoxanthine guanine phosphoribosyl transferase)
HISTOLOGICAL TYPES CHARACTERIZATION General Acute arthritis Dense neutrophilic infiltrate in synovium and fluid
Monosodium urate crystals within neutrophil cytoplasm
Chronic tophaceous arthritis Hyperplastic synovium with inflammatory cells and fibrosis, heavily encrusted with urate crystals Tophi Pathognomonic hallmark of gout
Large aggregations of urate crystals surrounded by epithelioid histiocytes and mononuclear cells and foreign body giant cells
Gouty nephropathy Deposition of urate crystals usually in renal medullary interstitium
May form tophi
CHARACTERIZATION Special stains De Galantha stain
Evaluation of Crystals in Formalin-Fixed, Paraffin-Embedded Tissue Sections for the Differential Diagnosis of Pseudogout, Gout, and Tumoral Calcinosis
Vinod Shidham, M.D., FIAC, MRCPath, Mamatha Chivukula, M.D., Zainab Basir, M.D. and Ganesh Shidham, M.D.
From the Department of Pathology (VSMC, ZB) and Division of Nephrology (GS), Medical College of Wisconsin, Milwaukee, Wisconsin
Mod Pathol 2001;14:806-810 Abstract quote
Hematoxylin-eosin (H&E)–stained sections may not allow proper evaluation of birefringence properties of the crystals in the lesions of pseudogout, gout, and tumoral calcinosis. This study was undertaken to verify the application of a special stain that could facilitate the evaluation of the birefringence properties of these crystals for definitive diagnosis.
We evaluated previously described nonaqueous alcoholic eosin staining (NAES) method based on the principle of using alcoholic eosin without hematoxylin and any other aqueous reagents for staining of formalin-fixed, paraffin-embedded tissue sections.
Two observers, in a blinded fashion, evaluated the sections stained with routine H&E and NEAS method without the knowledge about clinical diagnosis. All pseudogout (nine sections from seven cases) and gout (eight sections from five cases) lesions demonstrated birefringence in the sections stained with NAES method. H&E–stained sections showing the respective diagnostic histomorphology failed to demonstrate the birefringent crystals by polarizing microscopy in all the eight sections from gout and in seven of nine sections from pseudogout. Only two H&E–stained sections showed scant calcium pyrophosphate dihydrate (CPPD) crystals in pseudogout. None of the three sections from two cases of tumoral calcinosis showed birefringence with either stain.
We conclude that CPPD in pseudogout and monosodium urate in gout may not polarize in the routine H&E–stained sections. However, polarizing microscopy of sections stained with NAES method allowed demonstration of CPPD crystals with positive birefringence in pseudogout, MSU crystals with negative birefringence in gout, and calcium hydroxyapatite crystals without birefringence in tumoral calcinosis.
Section stained with NAES method is a significantly useful adjunct to the routine H&E stain for proper evaluation of the crystals under polarizing microscope in these lesions.
Polarized light examination Characteristic birefringent needle shaped crystals, negatively birefringent
PROGNOSIS AND TREATMENT CHARACTERIZATION Prognostic Factors Hypertension is common
Chronic gouty nephropathy may supervene
Survival 20% of chronic gout sufferers die of renal failure Treatment Xanthine oxidase inhibitors
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DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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