Clinical diagnosis
Case 254
【Progress】
DLST (drug-induced lymphocyte stimulation test) test for irinotecan was positive (328 > 180) that implied the allergy was caused by irinotecan. Cancer cell must untangle their double stranded DNA for proliferation. Irinotecan inhibits the enzyme to inhibit DNA untangle of cancer cell.
【Discussion】
Allergic immune reaction is to naturally repel the pathogen attack and preserve our body. However, it injures our body since immune potency is double-edged-bladed sword. It is largely categorized into four types: anaphylaxis (Type I), antibody response (Type II), antigen-antibody complex response (Type III) and delayed sensitivity (Type IV).
Anaphylaxis is an acute response to foreign body or toxin coming from histamine secretion from mast cells or basophilic cells most associated with Ig E which is produced from the previous pathogen contact, such as when contrast medium injection. Anaphylaxis without Ig E also occurs such as when bitten by hornet.
Antibody reaction is response of Ig M ( > Ig G) to destroy foreign body directly such as when mal-blood-type transfused.
Antigen-antibody complex is response of Ig G (> Ig M) with attraction of neutrophils or macrophages. Antigen-antibody complex immune reaction is sometimes continuous and serious with the respect that antigen can be self-component, indicating immune cells misjudge self-component is a foreign body and attempt to repel the self-component. Neutrophils take a part of repelling the self-component by phagocytosis and enhance the vessel permeability, inducing inflammation. It occurs such as when rheumatoid arthritis and lupus erythematosus onset.
Delayed hypersensitivity is a response by macrophages with lymphocytes to foreign body. They surround the foreign body to repel and absorb foreign bodies, inducing formation of nodule. It occurs when tuberculin skin test is tested or when Crohn disease onsets.
The allergy examples of antigen-antibody complex (type III) and delayed response (typeIV) described above are the immune response to extravascular foreign body. When more volume of foreign body than antibody volume enters in vascular lumen, one antibody adhere several antigens accumulate and deposit to capillary which induces migration of phagocytes and permeability of vessels inducing edema and micro-thrombosis to ischemic tissue damages.
In our case, anticancer drugs for distant metastasis from sigmoid colon cancer after surgical resection were continued. Laboratory test revealed the lymphocytes count decreased, the monocyte counts increased, platelets count decreased and chest CT showed multiple lesions with ground-glass opacity at bilateral pulmonary lobes. Continuous anticancer drugs administration indicates the continuous exposure of antigen volume and lymphocytes count decrease indicates less production of antibody, indicating accumulation and deposit of large antigen-antibody complex to capillary wall and monocytes infiltration count increase indicates phagocytic removal of the complex with enzyme secretion. Monocytes works high fever and elevation of CRP values. These immune responses stimulate permeability of capillaries and micro-thrombus formation, implying edema and ischemic alveolar damages, as shown ground glass opacity on chest CT and revealed the less count of platelets. Another story is the waste anticancer drug escaped by antibody might deposit to vascular wall and enhance the permeability of the vessels.
【Summary】
We presented a seventy two-year-old male with high fever and cough. He had undergone surgical sigmoid colon resection and got chemotherapy for distant metastasis. Chest CT revealed multiple lesions with ground glass opacity at both lobes. Laboratory test revealed monocytes count increased, lymphocytes count decreased, platelets count decreased and CRP value increased. It was borne in mind that fever and elevations of CRP value imply activation of macrophages, decrease of lymphocytes count implies less production of antibody and the decrease of platelets imply the formation of microthrombus with ischemic tissue damages. Allergic immune response is largely categorized into four types: anaphylaxis (Type I), antibody response (Type II), antigen-antibody complex response (Type III) and delayed sensitivity (Type IV). Of these, Type III reaction might be continuous and serious because self-component can be a foreign body repelling the self. It is postulated that drug induced lung disease is caused by more foreign body and less antibody causing accumulation of antigen-antibody complex deposit to the capillary wall (Type III) and macrophages infiltration to dispose the complex by phagocytes using enzymes (Type IV), inducing thrombus formation and capillary permeability that were shown as ground glass opacity on chest CT.
【References】
1.Shamitova E.N, et al. MECHANISM OF ALLERGY DEVELOPMENT IN HUMANS. European Journal of Natural History. 2019; 3: 56-60
2.Flieder D, Travis W. Pathologic characteristics of drug-induced lung disease. Clin Chest Med. 2004;25:37–45.
3.Limper A, Rosenow E. Drug-induced interstitial lung disease. Curr Opin Pulm Med. 1996;2:396–404.
2022.1.11