Serum Sickness

SERUM SICKNESS, a pathological condition of the organism caused by the parenteral administration of foreign serum and representing an expression of allergic sensitivity to foreign protein. The most frequent and characteristic symptoms of S. b. are pains in the joints, appearance of rash, elevation of temperature, swelling of lymphatic glands, and edema. In the 1870s, when transfusing the blood of lambs to patients for therapeutic purposes, the appearance of rash, febrile condition, and sometimes hemoglobinuria were observed. Since 1894, with the application of antidiphtheritic serum, attention was drawn to the appearance of rash, fever, swelling of glands, and joint lesions. In view of the fact that the predominant symptom accompanying serum administration was rash, the entire pathological phenomenon was initially called 'serum rash,' but the presence in addition to rash of a number of other symptoms gave full grounds to Pirke and Schick to name this disease 'serum sickness.' S. b. develops after the injection of therapeutic sera that cause in the human organism a state of heightened sensitivity to the repeated parenteral (and sometimes enteral) administration of foreign serum protein. Cases of S. b. are also observed when introducing human serum for therapeutic and prophylactic purposes (Belikov). Theories explaining the origin of S. b.—see Anaphylaxis. Phenomena of serum anaphylaxis may manifest in the form of rapidly developing anaphylactic shock directly after serum administration (see Anaphylaxis) or in the form of local anaphylaxis, usually observed in the first day after infusion in the form of rash and swelling of the skin around the injection site. S. b. occurs after a certain incubation period. The individuality of the patient, familial predisposition, individuality of the horse, duration of serum storage, and thoroughness of its purification from excess proteins play a large role in the manifestation of S. b. The amount of serum administered can also influence the intensity and duration of S. b. With heightened individual sensitivity to foreign protein, even the primary administration of horse serum can sometimes cause symptoms of serum sickness; its symptoms are observed much more frequently with repeated applications. Clinical picture. The phenomena of S. b. with primary serum administration appear after 8-12 days and usually express a complex of its symptoms, being limited in individual cases to the appearance of several, and sometimes even a single, symptom. One of the most frequent and vivid signs of S. b. is the appearance of rash. The rash most frequently appears at the site of serum administration, from where it can rapidly spread throughout the body, in other cases being limited to eruptions on separate areas of the skin. The rash usually causes itching and a burning sensation and can have the most varied character: most often it has the appearance of urticaria, sometimes annular, diffuse, erythematous, scarlatiniform, measles-like, exudative, polymorphous, and in severe cases hemorrhagic. It lasts from several hours to several days, in some cases extending up to two weeks, sometimes being limited to a single eruption, and in other cases taking a wavy course, now disappearing, now reappearing. S. b. is usually accompanied by swelling of lymph glands. Such swelling of glands, regional in relation to the injection site, is observed even before the appearance of rash, serving as an early sign for recognizing S. b. As S. b. develops, other groups of lymph glands—occipital, axillary, inguinal, etc.—become involved in the process. S. b. is more frequently accompanied by elevation of temperature, sometimes reaching high figures. Its type is usually remittent. Cases occurring with normal temperature are not infrequent. In S. b., edema of the skin, more frequently of the face, especially the eyelids and upper lip, sometimes of the scrotum, prepuce, and extremities, may be observed. Lesions of the joints in the form of arthralgia or swelling and painfulness, not progressing to suppuration, are encountered comparatively less frequently. Other symptoms characteristic of S. b. are observed even less frequently. In the urine, the presence of protein can sometimes be detected, while formed elements are usually not encountered. From the side of mucous membranes, pathological changes are usually not observed, and only in cases of sharply heightened sensitivity can redness and swelling of the soft palate, tongue, and tonsils, and especially the conjunctiva, be noted. Edema of the subchordal mucous membrane, which can be observed when using serum in lobar pneumonia patients, is accompanied by phenomena of a stenotic character. Pains of a diffuse and migratory character in the joints are extremely frequent. Sometimes typical myalgias are also noted. From the side of the gastrointestinal tract, vomiting and diarrhea may occur. Extremely rarely, depending on extremely heightened sensitivity, phenomena identifiable with the Arthus phenomenon (see Anaphylaxis), expressed by local edema, infiltration, and necrosis of the skin (Pirke and Schick, Jochmann), can be observed at the site of injection. In severe cases of S. b., enlargement of the liver and spleen (Balaban) is observed. In the incubation period of S. b., an increase in the total number of leukocytes can be noted, rapidly decreasing when the phenomena of the disease itself appear (Pirke and Schick). During S. b., leukopenia, in particular neutropenia, an increase in the number of eosinophils, and a decrease in the number of blood platelets are observed. At the same time, there is also a lowering of blood pressure. Heightened sensitivity to repeated serum administration is acquired, starting from the 8-12th day after the first administration, and can persist throughout life. With repeated serum administration, S. b. usually occurs after a shorter incubation period, and its symptoms are of a more intensely expressed character. With an interval between two infusions of 8-12 to 40 days, a sharply expressed, so-called immediate reaction, developing within the first day, can be observed; with an interval of over 6 months, S. b. occurs after a short incubation period of 3-5 days, the so-called accelerated reaction; with an interval of medium duration from 17 days to 6 months, either reaction can be observed. Patho-anatomical changes specific to S. b. are not noted. Recognition of S. b., in the presence of all its symptoms, especially in the presence of the most frequently encountered itching urticarial rash, presents no difficulties. Difficulties may arise with measles-like or scarlatiniform rash or with indistinctly expressed symptoms. Measles is excluded by the epidemiological history, absence of a prodromal period, catarrhal phenomena, and Filatov-Koplik spots. Scarlet fever is excluded by the absence of angina and the scarlet tongue. In those cases where S. b. manifests itself only by elevation of temperature, in the absence of other signs, the diagnosis has to be made by excluding all causes that might explain the observed febrile condition. The frequency of S. b. varies greatly among different authors. The smallest number—10%—is noted by Krichevsky, Jochmann; the figures of others are significantly higher and reach 45-50% (Piko), 47.5%-59.6% with primary serum administration and 96-100% with repeated administrations (Molchanova). With the current wide application of sera, the frequency of S. b. has naturally increased. Without great strain, it can be said that only a small number of persons treated with serum do not suffer in one form or another from S. b. Prognosis. The prognosis of S. b., except for phenomena of anaphylactic shock, is favorable, and the disease usually does not cause concern for its outcome, although it is sometimes accompanied by a 'threatening collapse' (Pirke and Schick). However, one should not exaggerate the possibilities of its appearance, since the human organism apparently does not belong to the number of easily sensitizable organisms (Krichevsky). The extremely rarely observed shock phenomena, individual cases of death after serum infusion, described by various authors, and the enormous therapeutic and prophylactic significance of sera fully justify their wide application. Therapy. Treatment of S. b. is symptomatic. Among the symptoms that can cause greater or lesser disturbance to the patient are the itching rash and painfulness of the joints. To alleviate the sensation of itching, local treatment in the form of rubbings with toilet vinegar, water with cologne, 1% solution of menthol, smearing with 1% menthol or veratrine ointments, dusting with talc can be applied. In cases of abundant and intensely itching rash, general measures are appropriate—lukewarm baths, cool wraps, subcutaneous injection of 1 cm³ of a solution of adrenaline (1:1,000) or 2-3 cm³ of 5% calcium chloride into the vein or the same medications orally. In cases of very severe S. b.—subcutaneous administration of physiological, Ringer's solution, or 5-10% solution of glucose. In joint lesions, warm compresses, phototherapy, heat are applied; in other cases, salicylates also have a beneficial effect. Prevention.

For the prevention of serum sickness, one should first strive to reduce the toxicity of the serum; for this purpose, it must be freed from excess proteins by heating to 56°, should be as concentrated as possible, and should be kept for no less than 2-3 months (Glukhov, Sadovsky, Chernov). To prevent or alleviate serum reactions, it is recommended to administer serum that has been heated and diluted (1:10) with physiological saline solution (Friedberger, Hartoch). For the purpose of desensitizing the body and bringing it into a state of anti-anaphylaxis, Bezredka proposed administering 0.5-1.0 cm³ of serum, and after four hours, the rest of the required amount (Bezredka, Friedberger and others). This method does not always prevent serum sickness, but it probably alleviates its symptoms, since the presence of anti-anaphylaxis only guarantees against the appearance of anaphylactic shock (Bogomolets). The use of intramuscular administration of 10-15% sodium hyposulfite in an amount of 10-20 cm³ simultaneously with the infusion of serum is harmless, reduces the frequency of serum sickness by 25-30%, and helps to decrease the number of severe cases of serum sickness (Glukhov, Sadovsky, Chernov). During the first week, in the absence of immediate or accelerated reactions, repeated administrations of serum are safe. If the interval is more than a week or there are serum reactions and at the same time there is a need for additional administration of serum, the proposed preventive measures should be applied, and in hospital practice, in cases where the most rapid effect from the serum is required, usually 0.5-1 cm³ is administered, and after 1-1½ hours the required amount of serum.