Porphyrias photosensitive

Poh-Fitzpatrick, M.B. (2000) Porphyrias photosensitivity and phototherapy, Methods Enzy-mol., 319 485 193. 

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. 

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). 

Porphyria In patients with porphyria, these drugs have precipitated an acute attack. Photosensitivity Photosensitization (photoallergy or phototoxicity) may occur. Renal/Hepatic function impairment Jse with caution. The frequency of renal complications is considerably lower in patients receiving the more soluble sulfonamides (sulfisoxazole and sulfamethizole). 

Adverse reactions may include the following Fever porphyria dysuria gout hepatic reaction nausea vomiting anorexia thrombocytopenia and sideroblastic anemia with erythroid hyperplasia vacuolation of erythrocytes increased serum iron concentration adverse effects on blood clotting mechanisms mild arthralgia and myalgia hypersensitivity reactions including rashes, urticaria, pruritus fever acne photosensitivity porphyria dysuria interstitial nephritis. 

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... 

Contraindications Concomitant disease states associated with photosensitivity (acute lupus erythematosus, porphyria, leukoderma of infectious origin), concomitant use of preparations with any internal or external photosensitizing capacity, hypersensitivity to trioxsalen or any component of the formulation... 

If a patient presents with blisters due to photosensitivity, a plasma scan and fecal porphyrins will not only reveal the presence of a porphyria, but will also enable the distinction between the three forms that may cause such symptoms porphyria cutanea tarda (PCT), PV, and HC. Urinary porphyrins and eventually quantitative ALA und PBG in urine may be added in questionable cases or for monitoring of therapy. 

Definition of porphyrias, their modes of genetic inheritance, and their treatment Porphyrias are caused by inherited (or occasionally acquired) defects in heme synthesis, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. Porphyrias are classified as erythropoietic or hepatic, depending where the enzyme deficiency occurs. With the exception of congenital erythropoietic porphyria, which is a genetically recessive disease, all the porphyrias are inherited as autosomal dominant disorders. All porphyrias result in a decreased synthesis of heme and, therefore, ALA synthase is dere-pressed. The severity of symptoms of the porphyrias can be diminished by intravenous injections of hemin. Because some porphyrias result in photosensitivity, avoidance of sunlight is helpful. 

Photoprotection is an inhibition of heme photosensitization via the quenching of photoreactive intermediates ( 02) by orally administrated P-carotene. Photoprotection concerns some kinds of porphyrias (the hereditary or chemically induced production of excessive amount of porphyrins in human and animals). Similarly as in photodynamic therapy, a raised concentration of porphyrins (Mb, Hg, cytochromes) causes the destruction of cells in the presence... 

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. 

Inherited defects or porphyrine biosynthetic enzymes can cause the accumulation of pathway intermediates that cannot be converted anymore with sufficient velocity. Various genetic forms of porphyria have been reported and result in liver toxicity, neurological damage and photosensitivity (75). Acquired forms of porphyria can be caused by a variety of toxic and pharmacologic agents. 

Uses. Sun screens are no substitute for light-impermeable clothing and sun avoidance. They are, however, beneficial in protecting those who are photosensitive due to drugs (below) or to disease, i.e. for photodermatoses such as photosensitivity dermatitis, polymorphic light eruption, cutaneous porphyrias and lupus erythematosus. Methodical use of sunscreens appears to reduce the incidence of squamous cell carcinoma in vulnerable individuals. 

This is a very rare form of chronic hepatic porphyria. As with PCT, the enzymatic defect is a deficiency of uroporphyrinogen decarboxylase. However, the genetic defect is homozygous. It may also be caused by exogenous factors. HEP manifests in early childhood with high photosensitivity, sclerodermia, hypertrichosis and anaemia. The liver shows red fluorescence. Histologically, siderosis and non-specific hepatitis are found. Development of cirrhosis is possible. No effective therapy is known. (314, 316)... 

Amiodarone commonly causes phototoxicity reactions (186,187). The risk of phototoxicity increases with the duration of the exposure. Window glass and sun screens do not give protection, although zinc or titanium oxide formulations and narrow band UVB photo therapy can help (188-190). For most patients this adverse effect will be no more than a nuisance, and the benefit of therapy may be worthwhile. However, in a few cases treatment may have to be withdrawn. Histological examination of skin biopsies shows intracytoplasmic inclusions of phospholipids (191). There has been a single report of a severe case of photosensitivity in conjunction with a syndrome resembling porphyria cutanea tarda, resulting in bullous lesions (192). 

Epstein JH, Tuffanelli DL, Seibert JS, Epstein WL. Porphyria-like cutaneous changes induced by tetracycline hydrochloride photosensitization. Arch Dermatol 1976 112(5) 661-6. 

The porphyrias are a heterogeneous group of diseases, all of which involve disorders of heme biosynthesis, which result in accumulation and increased excretion of porphyrins or porphyrin precursors. The porphyrias can be divided into two kinds the hereditary porphyrias, some of which can be exacerbated by exposure to certain chemicals, and the toxic porphyrias, which can be produced by exposure to certain chemicals alone. The pattern of excretion of porphyrins and porphyrin precursors is characteristic for each type. Clinical symptoms consist mainly of cutaneous photosensitivity and/or neurological disturbances. Hexachlorobenzene is a chemical inducer of porphyria. 

EPP is characterized by life-long acute photosensitivity caused by accumulation of protoporphyrin-IX in the skin. The absence of fragile skin, subepidermal bullae, and hypertrichosis distinguishes it clinically from all other cutaneous porphyrias. 

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