| disease | Serum Sickness |
| alias | Serum Sickness |
Serum sickness refers to an immune complex disease caused by the injection of heterologous immune serum, characterized by symptoms such as rash, fever, arthralgia, and lymphadenopathy. Currently, the clinical use of immune serum has significantly decreased and is limited to the prevention and treatment of diphtheria, tetanus, certain poisonous snake bites, and immunosuppressive therapy to prevent graft rejection. Nowadays, drug-induced sensitization has become the most common cause of serum sickness.
bubble_chart Pathogenesis
Serum sickness is a typical type III hypersensitivity reaction. The body can produce antibodies against various antigenic components of foreign serum introduced into the body or antigenic complex proteins formed by certain drugs acting as haptens binding with endogenous proteins. When the amount of antibodies formed is slightly less than the remaining antigens in the body, immune complexes that deposit on vascular walls can form, subsequently activating the complement system and generating vasoactive substances, neutrophil chemotactic factors, etc. This leads to local congestion and edema, infiltration of neutrophils, and release of proteolytic enzymes from lysosomes, resulting in tissue inflammation and injury. The antibody immunoglobulins constituting the immune complexes in serum sickness are mainly IgG, but if IgE is more abundant, the increase in serum permeability during the onset becomes more pronounced. Moreover, symptoms such as laryngeal edema, hypotension, or even anaphylactic shock may occur. Individuals who are more prone to producing both IgG and IgE antibodies under antigenic stimulation are also more susceptible to serum sickness.
Currently, the main serum preparations causing serum sickness in clinical practice include tetanus antitoxin, diphtheria antitoxin, various snake venom antitoxins, and antilymphocyte globulin (ATG). The drugs primarily responsible for serum sickness are penicillin, streptomycin, sulfonamides, salicylates, phenylbutazone, phenytoin sodium, as well as macromolecular drugs like dextran.bubble_chart Pathological Changes
The pathological manifestations of this disease are often similar to those of type III hypersensitivity reactions such as wind-dampness heat and nodular poly-stirred pulse inflammation, but the severity is milder. The main features include small vessel dilation, granulocyte infiltration, and edema. Autopsies were performed on three fatal cases caused by the administration of large doses of horse anti-cancer serum, revealing severe renal lesions characterized by ischemia, fibrin deposition, and infiltration of lymphocytes, neutrophils, and eosinophils.
bubble_chart Clinical Manifestations
This disease often occurs within 1 to 3 weeks after a single injection of a large dose of heterologous serum or globulin; a few patients, especially those with a history of similar serum vaccination, may experience onset within 1 to 3 days after inoculation. The occurrence and severity of symptoms are related to factors such as the route of inoculation (intravenous injection tends to trigger the
mechanism of disease more frequently) and the dose of serum administered. Skin rash is the most obvious and common symptom of this disease, primarily presenting as urticaria-like wheals, purpuric rashes, or measles-like rashes, often first appearing at the injection site. Fever typically develops gradually, peaking at 38–39°C, accompanied by varying degrees of generalized lymphadenopathy, which is soft and slightly tender. Some patients may also exhibit facial, eyelid, and extremity edema (more common in children), and very few may present with laryngeal edema. Some patients may experience abdominal pain, nausea, vomiting, and other symptoms concurrent with fever. For cases caused by serum or globulin (e.g., ATG) or other macromolecular drugs, joint pain, swelling, and other arthritic symptoms may appear around 2 days after the onset of the rash, often affecting multiple joints symmetrically. Severe complications such as polyneuritis, glomerulitis, or/and myocarditis are rare.
The most important diagnostic criteria for this disease are the history of serum or ATG injection and the aforementioned characteristic clinical manifestations. Small-molecule drugs rarely cause neuritis, glomerulitis, and/or systemic lymphadenopathy.
Laboratory tests are of limited help in diagnosing this disease. There is usually a moderate increase in the total white blood cell count, but eosinophilia is uncommon. Both total serum complement and C3 may decrease, and immune complexes may sometimes be found in the blood. Although these findings can aid in the diagnosis of this disease, they are not highly specific.
bubble_chart Treatment Measures
Generally speaking, the symptoms of this disease are not severe and are self-limiting. Therefore, treatment should primarily focus on symptomatic relief. For fever or arthralgia, salicylate preparations can be used. For those with rashes, diphenhydramine can be administered orally at 25–50 mg, 2–3 times daily, along with an intravenous injection of 10% calcium gluconate (10–20 ml) daily. Subcutaneous injection of 0.1% adrenaline (0.1–0.3 ml per dose) is highly effective for angioneurotic edema, dyspnea, or severe urticaria, and can be repeated every half hour if necessary.
Some reports suggest that administering sufficient antihistamines (cyproheptadine or hydroxyzine) to children between the 4th and 16th days after diphtheria antitoxin serum injection can significantly reduce the incidence of serum sickness.
For severe cases involving the nervous system, kidneys, or other internal organs, adrenal corticosteroids should be used. Adults may start with an intravenous injection of hydrocortisone (200–300 mg) or an equivalent oral dose of prednisone, with gradual dose reduction after 2–3 days based on the patient's condition.
Strictly adhere to the indications for the use of pharmaceuticals and serum immunologic products, and minimize the use of intravenous administration. If the use of heterologous serum products is necessary, first carefully inquire about any history of allergies or prior serum use, and then perform a skin sensitivity test as follows: ① Place an undiluted drop of serum on the flexor side of the forearm, then use a sterilized needle tip to make several scratches within the serum drop (without drawing blood); ② Observe for half an hour. If no reaction occurs, administer 0.1 ml of a 1:10 diluted serum intradermally; ③ Observe for another 20 minutes. If the injection site does not develop a wheal or induration exceeding 1 cm in diameter, or if no pseudopod-like papules appear around it, the result is considered positive, and the serum can then be administered intramuscularly.
If the skin test is positive, the serum should ideally be avoided. If its use is absolutely necessary, a purgative method for desensitization may be employed: ① First, administer an antihistamine orally (25–50 mg); ② After half an hour, inject 0.1 ml of serum diluted 20-fold subcutaneously; ③ Wait 20 minutes, then inject 0.1 ml of serum diluted 10-fold subcutaneously; ④ If no reaction occurs after another 20 minutes, inject 0.1 ml of undiluted serum subcutaneously; ⑤ Observe for 15 minutes. If no reaction is observed, proceed to inject 0.2 ml, 0.5 ml, 1.0 ml, and 2.0 ml subcutaneously at 15-minute intervals, followed by the remaining dose subcutaneously or intramuscularly.
During desensitization and serum injection, ensure that adrenaline and adrenocortical hormones are readily available to prevent anaphylactic shock. At any point during desensitization, 0.1–0.3 ml of 0.1% adrenaline may be administered subcutaneously as needed to counteract potential reactions. After completing the desensitization process and administering the remaining dose, closely monitor the patient for 1–3 hours to watch for delayed reactions.
