• Metabolic disorder in which there is hyperuricemia due to increased production and/or decreased excretion of uric acid; often idiopathic but secondary causes include renal insufficiency and medications such as diuretics or cyclosporine; affects primarily adult men.

• Crystals of monosodium urate can deposit within the skin (tophi) as well as the joints and kidneys; when expressed from the skin or aspirated from the joints, the crystals are needle-like and exhibit negative birefringence under polarized light.

• Tophi present as firm skin-colored to white or yellow papules and nodules, usually around joints and on the helices of the ears (Fig. 40.1); in general, they appear ~10 years after the initial episode of acute arthritis and occur in ~10% of patients with gout.

• Tophi can become inflamed (Fig. 40.2), and they may or may not resolve following normalization of serum uric acid levels.

• DDx: rare cutaneous involvement in pseudogout (rhomboid crystals) as well as calcinosis cutis, xanthomas, and rheumatoid nodules.

• Rx for tophi: diet, allopurinol, febuxostat; for refractory disease, pegloticase, IL-1 antagonists (e.g. rilonacept).

• Autosomal recessive disease due to loss-of-function mutations in ECM1, which encodes extracellular matrix protein 1; the result is deposition of hyalin-like material in multiple sites, in particular the brain (seizures) and larynx (hoarseness), as well as the skin and oral mucosa.

• Skin-colored to yellowish waxy papules and nodules favor the face, including the eyelid margin, and the tongue (Fig. 40.3); atrophic scarring, verrucous changes (especially on the elbows and knees), and a diffuse waxy appearance are additional findings; during infancy, fragility, vesicles and crusting of the face, extremities and mouth can occur.

• DDx: mucinoses, erythropoietic protoporphyria, primary systemic amyloidosis, colloid milium, and in infants, hyaline fibromatosis syndrome.

• Two major variants – inherited juvenile form and acquired adult form; because the latter is related to cumulative photodamage, it occurs primarily in adults with lightly pigmented skin.

• Dermal deposits lead to dome-shaped, translucent to yellowish papules in chronically sun-exposed sites, in particular the face, ears, posterior neck, and dorsal aspect of the distal extremities; the lesions can become nodular or even pigmented if topical agents such as hydroquinone have been applied.

• DDx: similar to that of lipoid proteinosis (see above).

• Rx: laser, cryosurgery.

• Group of inherited metabolic disorders in which there is an accumulation of glycosaminoglycans (GAGs; previously referred to as mucopolysaccharides) due to deficiencies in lysosomal enzymes that break down sulfated GAGs (e.g. heparan sulfate, dermatan sulfate).

• The accumulation of GAGs can lead to mental retardation, hepatosplenomegaly, skeletal and joint disease, corneal clouding, and a coarse facies; in addition to thickening of the skin, some patients have hypertrichosis; in Hunter syndrome (MPS II), grouped skin-colored to white papules can develop in the scapular region (‘pebbling’), and in Hurler syndrome (MPS I), patients may have dermal melanocytosis.

• Following measurement of urinary GAGs and examination of peripheral leukocytes or dermal fibroblasts for vacuoles, genetic analyses can be performed.

• Rx: for some of the types (MPS I, II, VI), enzyme replacement therapy is available; hematopoietic stem cell transplant (HSCT) is another option.