Skin porphyria

Under chronic intoxication, late skin porphyria is added to the above diseases. This syndrome is characterized by increased excretion of carboxylated porphyrins, coverlet pigmentation, photosensitivity, intes-tinal and nervous disorders. Toxic carboxylated porphyrins and ions of iron, not included into porphyrin structure, are accumulated in the cells of various organs. 

Cam C (1958) Cases of skin porphyria related to hexachlorobenzene intoxication. Saglik Dergisi, 32 215-216. 

These dru are contraindicated in patients with known hypersensitivity. Hydroxychloroquine is contraindicated in patients with porphyria (a group of serious inherited disorders affecting the bone marrow or the liver), psoriasis (chronic skin disorder), and retinal disease (may cause irreversible retinal damage). MTX is contraindicated during pregnancy because it is a Pregnancy Category X dmg and may cause birth defects... 

The toxic effects of the fungicide and environmental pollutant hexachlorobenzene (HCB) were first noted in the 1950s when people were exposed to high doses of HCB through intake of contaminated grain. Intoxicated individuals developed a variety of symptoms including hepatic porphyria, skin lesions, and arthritis. Symptoms were accompanied by infiltrates of inflammatory cells [11, 33],... 

Certain disease states also produce alterations in the skin s optical properties. Alterations of the skin s surface, such as by psoriatic plaques, decrease transmitted fight. The effect may be lessened by application of oils whose refractive index is similar to that of skin (Anderson and Parrish, 1981). Disorders such as hyperbilirubinemia, porphyrias, and blue skin nevi result in increased absorption of visible light due to accumulation or altered distribution of endogenous chromophoric compounds. 

Porphyrias That Involve Photosensitivity, Inflammation and Blistering of Skin... 

Deficiencies of other enzymes in the heme pathway produce porphyrias in which photosensitivity is a common finding. Chronic inflammation to overt blistering and shearing in exposed areas of the skin characterize these porphyrias. The most common is porphyria cutanea tarda (deficiency of uroporphyrinogen decarboxylase). 

There are a large number of hereditary or acquired disturbances of porphyrin synthesis, known as porphyrias, some of which can cause severe clinical pictures. Several of these diseases lead to the excretion of heme precursors in feces or urine, giving them a dark red color. Accumulation of porphyrins in the skin can also occur, and exposure to light then causes disfiguring, poorly healing blisters. Neurological disturbances are also common in the porphyrias. 

Caution [B (D if near term), M] Contra Sulfonamide or salicylate sensitivity, porphyria, GI/GU obst avoid in hepatic impair Disp Tabs SE GI upset discolors urine dizziness, HA, photosens, oligospermia, anemias, Stevens-Johnson synd Interactions T Effects OF oral anticoagulants, oral hypoglycemics, MTX, pheny-toin, zidovudine X effects W/ antibiotics X effects OF digoxin, folic acid, Fe, procaine, proparacaine, sulfonylureas, tetracaine EMS T Effects of anticoagulants monitor EGG and BP for signs of hypovolemia and electrolyte disturbances d/t D skin urine may become yellow-orange may stain contact lenses T risk of photosensitivity Rxns OD May cause NA, drowsiness, HA, abd pain, skin Rxns, lactic acidosis, and jaundice symptomatic and supportive... 

For idiosyncratic, patient related adverse reactions, less confirmatory tests are available but the number is growing. Skin, blood and urine tests are available to confirm acute and chronic allergic reactions. Genetic tests can determine the susceptibility of individuals and includes general tests such as for the porphyrias and sickle cell anaemia, and specific tests for dmg metabolism, such as acetylator status... 

Hydroxychloroquine is approved for the treatment of both systemic and cutaneous lupus erythematosus. Both chloroquine and quinacrine (Atabrine) are also effective in this skin disease. Low-dose chloroquine is used for the therapy of porphyria cutanea tarda in patients in whom phlebotomy has failed or is contraindicated. Other skin diseases in which the drugs are useful (after sunscreens and avoidance of sun exposure) include polymorphous light eruption and solar urticaria. 

Individuals affected with porphyria present with acute attacks, skin lesions, or both. The onset of these attacks rarely occurs before puberty. An attack usually consists of severe abdominal pain and often neurological sequelae. During and after such attacks, excessive amounts of aminolevulinic acid and PBG are excreted in the urine. The most common porphyria is PBG deaminase deficiency (acute intermittent porphyria), which primarily affects liver function. A positive result coupled with a clinical indication of hepatosplenomegaly suggests that evaluation for tyrosine metabolites in the urine should be pursued (using the nitrosonaphthol test). 

One of the rarer porphyrias results in an accumulation of uroporphyrinogen I, an abnormal isomer of a protoporphyrin precursor. This compound stains the urine red, causes the teeth to fluoresce strongly in ultraviolet light, and makes the skin abnormally sensitive to sunlight. Many individuals with this porphyria... 

Skin eruptions in a patient with porphyria cutanea tarda. 

Erythropoietic porphyrias The erythropoietic porphyrias (congenital erythropoietic porphyria and erythropoietic proto porphyria) are characterized by skin rashes and blisters lhat appear in early childhood. The diseases are complicated by cholestatic liver cirrhosis and progressive hepatic failure. 

The deaths of breast-fed infants in the mid-fifties in Turkey, and an epidemic of skin sores and discolorations (porphyria cutanea tarda) were associated with the accidental consumption of HCB-contaminated seed grain (refs. 93-910 Clinical symptoms included weight loss, enlargement of lymph nodes and thyroid, abnormal growth of body hair and skin photosensitization. 

Inborn metabolic diseases that interfere with heme biosynthesis are called porphyrias. Porphyrias have a variety of symptoms. A deficiency in the enzyme responsible for the condensation of porphobilinogen to the 4-membered ring system leads to a condition called acute intermittent porphyria, which is characterized by occasional episodes of abdominal pain and psychiatric symptoms. Defects in the later enzymes of the pathway lead to an excess accumulation of the uroporphobilinogens in the tissues, where they cause a variety of symptoms, including hairy skin, skeletal abnormalities, light sensitivity, and red urine. Individuals with this disease are still anemic—a condition that can be alleviated somewhat by the heme acquired from drinking blood. This combination of traits sounds like the werewolf and vampire legends of Europe, which may have their base in this rare biochemical disease. 

Porphyria, the disease from which Britain s King George III is believed to have suffered, arises through the accumulation of porphyrin decomposition products in the skin due to impaired enzyme function in the haem biosynthetic pathway [5], In addition to many other unpleasant side effects, porphyria renders the individual highly sensitive to light. The effects of porphyria, if they could be controlled and directed towards particular diseased tissue, would have the potential as a powerful therapeutic method. As the mechanism involves local, light-initiated generation of... 

Bonkowsky HL, Bloomer JR, Ebert PS, Mahoney MJ (1975) Heme synthetase deficiency in human protoporhyria Demonstration of the deficit in liver and cultured skin fibroblasts. J Clin Invest 56 1139-1148 De Vemeuil H, Aitken G, Nordmann Y (1978) Familial and sporadic porphyria cutanea two different diseases. Hum Genet 44 145-151... 

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