Gout

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.

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/ Immunohistochemistry/ Electron Microscopy
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
Cutaneous zygomycosis associated with urate panniculitis. Vernon SE, Dave SP. Department of Pathology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.	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
VARIANTS

SPECIAL STAINS/ IMMUNOPEROXIDASE/ OTHER	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 Colchicine