Acute Radiodermatitis

 For descriptive purposes three degrees of acute dermatitis are usually designated: 

First Degree Radiodermatitis. This is the mildest form of inflammatory reaction. It consists of an erythema associated with slight burning and itching, which entirely disappears after a few days or weeks, either leaving no trace or being followed by alopecia, pigmentation or slight desquamation.

     Sequelae. First degree reactions are generally followed by epithelial desquamation, pigmentary changes, and temporary or permanent dryness due to impairment of the sweat and sebaceous glands or alopecia. After the course of months, usually about eighteen months subsequent to treatment, but sometimes as early as twelve months or as late as ten years, slight cutaneous atrophy accompanied by telangiectasia is likely to supervene.

      Second Degree Radiodermatitis. In radiodermatitis of the second degree the erythema is more marked and the edema so intense that vesiculation results. Itching and burning are pronounced. The erythema of second degree reactions develops two or three days earlier than in the case of first degree reactions. At the beginning the color is scarlet. In the course of a few days the edema becomes intense, causing exudation, vesiculation, and erosion of the epidermis. Crusting of an impetiginous character ensues; hair in the irradiated area falls out about three weeks after exposure. The alopecia is likely to be permanent. The function of the sebaceous and sweat glands is impaired for an indefinite period in most cases. When the fingers are affected, the nails may desquamate.

         The duration of second degree reactions is, as a rule, between one and three months. Several months after healing, atrophy and telangiectases are likely to ensue. It is not uncommon for the skin to assume a parchment paper appearance. In the course of time lentiginous spots and keratoses usually develop, and after years, cancer also.

         Third Degree Radiodermatitis. When the reaction is severe enough to cause necrosis and ulceration, it is classified as third degree radiodermatitis. With modern methods, local injuries of this kind from x-rays rarely occur. Such a roentgen accident generally results from carelessness. On the other hand, with unfiltered or lightly filtered radium or supersoft x-rays, the necrosis which leads to ulceration is often purposeful and therapeutic.

         As with the other degrees of reaction, the time of onset is inversely proportional to the magnitude of the dosage and the softness of the radiation. The reaction causes vivid erythema, edema, vesicle or bulla formation, pain, and sloughing. The pain is especially severe when cartilage, periosteum, or bone is involved. With soft radiation vesiculation always precedes ulceration by a few hours or days. With hard radiation the breaking down of tissues into an ulcer may follow an erythema and vesiculation so transient that neither is marked; consequently necrosis comes on suddenly, without much forewarning. This is especially apt to happen when cross-firing has been employed. Healing is delayed at least for months, often indefinitely. When cartilage or bone is involved it does not take place until the sequestra are removed. When healing does occur the resultant scar is dry, shiny, hairless, atrophic, telangiectatic and liable to break down spontaneously or from the slightest trauma.

         Ulcerations of this character are so indolent that they frequently never heal. They are subject to secondary infection, and after years of irritation from this cause, from local remedies and motion of the injured part, cancer springs into existence.

In cases in which the reaction has been caused by penetrating radiation, the injury to the subcutaneous connective tissue is so severe that a dense, rather diffuse local sclerosis or "boardlike thickening" occurs. These sclerodermatous changes may limit the motion of articulations. The tissue is practically avascular, due to a destructive endarteritis of the vessels. Ulcerations which develop in such environments from either trophic or minor mechanical causes are naturally indolent and subject to malignant changes. In severe cases the vascular damage is so pronounced that gangrene may result.

Local Clinical Reactions

Pigmentation following radiation is especially influenced by individual characteristics. It is common after reactions of all degrees. In brunets diffuse homogeneous tanning may ensue from a fractional unfiltered roentgen treatment. A similar small exposure may produce numberless ephelides of various sizes and depths of brownish color in those subject to freckles. In some the freckles may be of light brown color and rather large; in others they may be very dark brown or black and pinhead-sized.

     Pigmentation or tanning usually disappears in a few weeks but may persist much longer. Not infrequently the hyperpigmentation endures for a few years, especially in brunets. After very severe reactions the pigmentation may be permanent.

     In dark skins, especially in Ethiopian and Mongolian races, depigmentation instead of hyperpigmentation may ensue from intensive exposures. Such depigmentation is permanent. It must be particularly guarded against in the treatment of keloids, where it is customary to use fairly large doses.

     Hyperpigmentation, either diffuse or in the form of ephelides, is not an important index of skin toleration, but it should not be completely disregarded in the treatment of acne and other benign dermatoses where cosmetic effects are important. Cases which show an early tendency to pigmentation should receive a little more conservative treatment than those in which this biologic reaction is not manifest.

     Cutaneous Changes Representing the Transient Functional Inhibitions Which, During Fractional Treatment, Precede the Onset of True Radio-dermatitis. Although mild in character, they are of the greatest importance in roentgen therapy, because they are about the only clinical means of estimating the biologic response of normal skin structures (sebaceous and sweat glands, hair follicles, and blood vessels) to doses which are suitable for the radiotherapy of benign dermatoses.

     Inhibition of Functional Activity. The mildest form of clinical reaction is a dryness of the skin caused by inhibition of the activity of the sudoriferous and oil glands. This effect—which may be temporary or permanent—is noticed chiefly in treatment with small doses over a long period at short intervals. Permanent inhibition may result from repeated fractional filtered exposures of x-rays or radium without causing an erythema.

     Dryness denotes that almost an erythema dose has been administered, and serves as a warning that further radiation must be given cautiously with close observation of the skin for evidence of irritability or erythema.

     Epilation. The hair is epilated by suberythema exposures of all except very soft radiation Lanugo, scalp and other hair are affected. Defluvium usually occurs sixteen to twenty-one days after the administration of an epilating dose. About the fourth week after exposure the hair ceases to fall.

     Defluvium from suberythema exposures is always temporary. Even if there are mild reactions the hair will usually regrow. It is necessary to bear in mind that an erythema, however mild, may not be followed by complete regeneration. Erythemas are therefore to be avoided in cases requiring temporary epilation.

     Quality of radiation also affects the character of these mild reactions. With soft radiation from beryllium window tubes and grenz rays the action is so superficial that the hair follicles are not appreciably affected. As a result, this reaction consists of a superficial erythema. It appears within a few hours after treatment and disappears in the course of one or two weeks. Erythemas from unfiltered radium may also be so superficial that they do not cause epilation. With orthodox qualities of radiations, defluvium occurs with all doses sufficient to produce an erythema.

     Permanent alopecia is apt to follow severer types of radiodermatitis and even well-marked erythemas, although occasionally a few scattered coarse hairs are seen growing in atrophic, telangiectatic areas which have resulted from large doses.

     Regrowth of hair usually occurs without delay. Frequently it begins to grow in two or three weeks after it has fallen. In general it may be said that regeneration takes place one to four months after treatment. However, in cases which have shown no growth in this time, some coarse hair may grow years later.

     The regrowth following even small doses may differ slightly from the original. Frequently it is more profuse and occasionally it is curly in instances where it was formerly straight, or may have a slightly different color or luster. It may grow more rapidly and profusely in previously diseased areas than upon normal skin.

     Irritability. The serial administration of small doses of radiation may eventually lead to a pronounced vascular irritability of the skin resembling a mild degree of dermographism. In this state, rubbing or slapping of the treated area or the application of warmth gives rise to rapid hyperemia. There may or may not be slight itching.

     Skin irritability of this nature results from a larger dose than is required to produce inhibition of the sweat and sebaceous glands. It may occur with an epilating dose, especially if attempts at permanent epilation are under-taken. The greatest importance attached to this type of skin irritability lies in its significant warning that an erythema may develop at any time.

     The local clinical reactions which have been described are not usually included in a definition of radiodermatitis. Inflammatory conditions of the skin produced by roentgen rays or radium rays (radiodermatitis) are best divided into (a) acute dermatitis from a single large dose or multiple large doses given at short intervals, and (b) chronic dermatitis as a sequel of acute dermatitis or from frequently repeated small doses given over a long period.

Roentgen And Radium Dermatitis

Dermatitis due to these agents may be intentionally produced by an accurately controlled technique when warranted in the treatment of certain diseases, or may be accidentally incurred by ignorance or carelessness. Accidental "burns" from x-rays and radium were closely associated with the early use of them and, in the case of radium, first called attention to its action upon living matter. About five years after the discovery and medical use of roentgen rays, the first case of cancer arising upon chronic radiodermatitis was reported in a roentgenologist. During the succeeding few years numerous cases appeared in the literature. Although the x-ray industry has since that time grown, the dangers are now more fully recognized and precautions against them have been adopted.

       Similarity Between Radium and X-ray Dermatitis. Inflammatory reactions due to x-rays and radium have many points of similarity, although the onset, course, and end results vary greatly. These variations depend upon the intensity and penetration of the radiation.

 Latent Period. An interval of several days intervenes between the exposure to radiation and the onset of visible skin reaction. This interval is called the latent period. The term is applied mostly when erythema doses are used, but a similar interval exists between exposure and functional or therapeutic manifestations when fractional or suberythema doses are employed. The duration of this interval is affected largely by the quality of the radiation, the skin tolerance of the subject, and the magnitude of the dose. In general, the softer the radiation and the larger the dosage, the shorter is the latent period.

     The phenomena of the latent period are difficult to explain. They belong to the field of general biology and are not a specific radiation problem. Presumably the radiation effects are immediate, and such grossly visible clinical changes as ultimately appear are tissue reactions to them. 

Porphyria

Porphyria occurs in three forms. Congenital porphyria appears early in childhood as a fault of the pigment metabolism, possibly inherited as a mendelian recessive. There is hypersensitivity of the skin to sunlight in spring and summer showing as hydroa aestivale. Blisters develop on exposed parts of the face and extremities and may heal with scarring. There is a reddish or purplish brown discoloration of the teeth and bones due to impregnation with uroporphyrin I. Large amounts of uroporphyrin are excreted in the urine giving it a reddish color and causing it to fluoresce when exposed to ultraviolet light; fluorescence of the fingernails and teeth also shows. A variety of congenital porphyria is porphyria cutanea tarda.

      Porphyria cutanea tarda is a relatively rare inherited fault of pyrrole metabolism characterized by the excretion of various types of porphyrin, mostly uroporphyrin. There are two types. The erythropoietic type is a form of blood dyscrasia with the site of origin in the bone marrow. There are mutilating photosensitivity, splenomegaly, hemolytic anemia, erythrodontia, hypertrichosis and melanosis. Treatment is by splenectomy. The hepatic type arises in the liver, apparently due to a genetic enzymatic disturbance. There is no evidence of consanguinity, but there are signs of impaired liver function. Many of the patients that Brunsting reported in childhood had red hair that turned dark or black in later life. There was frequently a history in older people of the darkening of gray hair. There were blisters and crusted lesions, not always related to exposure to light. Sclerodermatous patches were often noted. There was a history of colic, hypertension, melanosis, paresis or paralysis, and aggravation by drugs and alcohol. In the hepatic type there is no hemolytic disease.

       Acute porphyria manifests itself by gastrointestinal symptoms and nervous system involvement. There is often agonizing abdominal pain that may come and go rather rhythmically. It may be in the upper abdomen or in the loins and associated with vomiting, constipation, icteric tinge to the conjunctivae, anxiety, crying, perplexed syndromes, paralyses and convulsions.

       There may be spotted pigmentation, but the skin is little affected and patients rarely show light sensitivity. The urine has a characteristic pink color, which does not develop immediately but is most evident after forty-eight hours. Porphyrins are excreted in excessive amounts. Uroporphyrin III is excreted in very large amounts chiefly during attacks. Smaller amounts of coproporphyrin III or I are found occasionally. Microscopically there may be patchy degeneration of the myelinated fibers of the nerve roots of the cord white matter. Petechial hemorrhages and areas of focal necrosis occur in the brain. The etiology is obscure, and no treatment has been established. Glucose and thiamine may be given intravenously.

       Chronic porphyria includes those cases that cannot be classified as congenital or acute, but exhibit the clinical symptoms of both in a milder form. The face and neck have a bluish cast. In chronic porphyria the skin is sensitive to light Sclerodermatous thickening occurs in the cheeks and back of the neck. Gastrointestinal, nervous and mental symptoms occur, either singly or in combination. Acute toxic porphyrinuria caused by certain toxic substances and drugs should not be included. Chronic porphyria is characterized by excessive excretion of coproporphyrin III and I and uroporphyrin III and I. Chronic porphyria is a disturbance of metabolism with hereditary aspects, and may be latent for a long time, as in diabetes. Chronic alcoholism is often a precipitating factor. In almost all cases there is failure to demonstrate hypersensitivity to any of the fractions of the spectrum by artificial tests. The treatment of porphyria, in a broad sense, is that of cirrhosis of the liver. Intramuscular injections of 2 to 5 cc. of crude liver extract two or three times a week are beneficial.