Deposition and Metabolic Diseases

Porphyria cutanea tarda (PCT): most common type of porphyria, uroporphyrin decarboxylase deficiency, most cases acquired and only 20% due to UROD gene mutation, uroporphyrins highly elevated in the urine, “tarda” refers to “late” (adult) onset of vesicles , papules, crusts, and milia in areas of scarring, most common on the dorsum of the hands (1.56), malar hypertrichosis (1.62), sometimes associated with HIV, most cases associated with hepatitis C (14.7), alcohol abuse, and liver disease (1.75) with iron accumulation. Can be associated with hemochromatosis and HFE gene defect (8.17):

• ■

  Subepidermal blister with viable roof, festooning of dermal papillae (very well-preserved papillae projecting into blister), and very little inflammation ( cell poor ).

• ■

  Caterpillar bodies (eosinophilic, linear, segmented basement membrane material resembling dyskeratotic cells; 1.27) sometimes found in the roof of the blister, not specific for porphyria.

• ■

  Sparse hyalinized material around blood vessels (PAS positive, diastase resistant), especially in papillary dermis, sometimes throughout dermis.

• ■

  Dermal sclerosis in late stages sometimes (1.125).

• ■

  Direct immunofluorescence: IgG and C3 around papillary dermal vessels with lesser staining at dermal–epidermal junction in the lamina lucida.

Acute intermittent porphyria (AIP): rare, hydroxymethylbilane synthase (formerly porphobilinogen deaminase) deficiency, autosomal dominant, associated with HMBS gene mutation, increased porphobilinogen (PBG) in the blood, acute abdominal pain, psychosis, neurologic disease, no skin lesions .

Variegate porphyria (VP): protoporphyrinogen oxidase deficiency, autosomal dominant, usually PPOX gene mutation, combined features of AIP plus PCT .

Hereditary coproporphyria (HCP), autosomal dominant, and harderoporphyria, autosomal recessive: rare, mutation in CPOX gene, coproporphyrinogen oxidase deficiency, combined features of AIP plus PCT .

Erythropoietic protoporphyria (EPP): rare, ferrochelatase deficiency, autosomal dominant, often associated with FECH gene defect (X-linked dominant EPP may be associated with ALAS2 gene), photodermatitis with very few blisters begins in childhood , occasional fatal liver disease, free erythrocyte protoporphyrin elevated in the blood, impressive deposits of hyalinized material, PAS-positive, in the dermis, less blistering.

Congenital erythropoietic porphyria (CEP, EP, Günther’s disease): very rare, uroporphyrinogen III synthase deficiency, autosomal recessive, often UROS gene mutation, severe congenital mutilating “ werewolf ” form with onset in infancy, red fluorescent teeth, extensive hypertrichosis, hemolytic anemia, splenomegaly, more hyalinized material in dermis than other forms of porphyria (1.35).

Pseudoporphyria: related to hemodialysis or certain drugs (3.5), especially non-steroidal anti-inflammatory drugs, tetracycline, and furosemide, nearly identical to PCT histologically.

Other diseases with abundant dermal eosinophilic amorphous pink material (1.35) may resemble EPP, especially lipoid proteinosis (8.3) and amyloidosis (8.4).

Other subepidermal blistering diseases (1.147; Chapter 6 ), especially the more cell-poor ones such as epidermolysis bullosa (6.6), bullous amyloidosis (8.4), and some examples of bullous pemphigoid (6.1).

Other diseases with amorphous pink material (1.35), especially amyloidosis (8.4) and nodular colloid degeneration (9.1).

Juvenile hyaline fibromatosis: very rare, autosomal recessive, due to CMG2 (capillary morphogenesis gene-2) or ANTXR2 (anthrax toxin receptor) mutation, deposition disorder affecting young children, mental retardation, no hoarseness, flexural contractures , gingival hypertrophy , papules or nodules on the lips (1.74), nose (1.95), ears (1.28), and perianal areas (1.108). PAS and Alcian blue positive hyalinized dermal deposits with a chondroid appearance.

Infantile systemic hyalinosis: somewhat like juvenile hyaline fibromatosis with same genetic defect reported, but there is more systemic involvement.

Other diseases with amorphous pink material (1.35), especially amyloidosis (8.4) and erythropoietic protoporphyria (8.1).

Primary systemic amyloidosis: AL types of amyloid with immunoglobulin light chains (usually lambda) deposited, associated with myeloma (24.12), yellowish (1.151) or purpuric (1.120) macules or plaques, mostly in the elderly , especially on the eyelids (1.43), deposits diffuse in dermis and/or especially around blood vessels , sweat glands, and adipocytes, often with scattered lymphocytes, plasma cells (1.111), and extravasated erythrocytes (1.40). Special immunostains for light chains usually positive, but can also be positive by non-specific absorption in macular and lichen amyloidosis.

Secondary systemic amyloidosis: AA type of amyloid (serum derived) associated with chronic systemic diseases such as rheumatoid arthritis or leprosy, no skin lesions usually present clinically, but patients have deposits of amyloid in other organs. Dermatologists are sometimes asked to biopsy “normal” lower abdomen skin to find subtle amyloid around blood vessels, sweat glands, or fat cells, obviating the need for rectal biopsy or internal organ biopsy.

Nodular amyloidosis: large waxy nodule of diffuse light chain AL amyloid in the dermis, plasma cells usually present (1.111), with systemic amyloidosis or myeloma in a minority of cases.

Bullous amyloidosis: rare form of systemic amyloidosis with hemorrhagic (1.120) cell-poor blisters (1.147), amyloid deposits may be subtle or prominent. Amyloid can act as a sponge for IgM or C3, which may cause confusion with autoimmune blistering disorders such as pemphigoid when direct immunofluorescence is performed.

Lichen amyloidosus (technically the only form of amyloid spelled with the ending –us due to Latin derivation): pebbled lichenified plaques, mostly on the shins or scattered grouped papules in areas that are chronically rubbed, without systemic disease, small deposits of amyloid limited to dermal papillae , often melanin incontinence (1.79), may resemble or may be a variant of lichen simplex chronicus (2.3).

Macular amyloidosis: brown macules (1.17) with a rippled appearance (“hammered brass” or “corduroy pants”), most common on the upper back (1.141), without systemic disease, nearly normal epidermis, very subtle amyloid blobs in the papillary dermis in areas of melanin incontinence (1.79), biopsy may appear nearly normal (1.94).

Muckle–Wells syndrome: rare, autosomal dominant, mutation in CIAS gene encoding cryopyrin, urticaria, deafness, and AA amyloid in kidney.

Familial Mediterranean fever: rare, autosomal recessive, fever, peritonitis, pleurisy, arthritis, cellulitis-like plaques of the legs, AA amyloid in kidney.

Other diseases with amorphous pink material (1.35), especially porphyria (8.1), colloid milium (8.2), lipoid proteinosis (8.3), and Waldenström’s macroglobulinemia (24.12). Because special stains can be variable, electron microscopy may be desirable if proof of amyloid deposits is desired.

Most of the other amorphous pink materials in Section 1.35 are not surrounded by a giant cell infiltrate, and do not show the subtle needle-shaped crystals.

Other juxta-articular nodules (1.92), especially calcinosis cutis (8.15) rheumatoid nodules (7.3).

Other diseases with increased mucin in the dermis (1.83), or a nearly normal appearance (1.94).