Age: 3.0
Sex: F
Vaccine: FLUX
Symptoms: Puncture site haemorrhage, Pupillary light reflex tests abnormal, Rales, Red blood cell count normal, Respiratory arrest
Clinical narrative: Case number PHHY2016US023690, is an initial literature case report received on 22 Feb 2016. The author discussed about the fatal allergic reaction due to influenza vaccine. This report refers to a 42-month-old female patient. Past drug history included acetylsalicylic acid and the patient experienced hives for one day during the first year of life which were thought to follow medication. There was no history of asthma and no family history indicative of allergy could be elicited. Prior to the injection of the vaccine the physician had attempted to obtain a history of allergy to eggs or chicken with negative results. Concomitant medication was not reported. The patient was vaccinated with seasonal influenza vaccine (manufacturer and batch number: not reported) subcutaneously at a dose of 0.5 ml on an unknown date. The patient complained of pains in the abdomen and chills followed by vomiting and convulsions four hours after the vaccination. On examination the patient had a rectal temperature of 109 F. The patient was hospitalized within two hours after the onset of symptoms. On admission to the hospital the patient showed pronounced cyanosis, pupils were widely dilated and unresponsive to light. The lungs showed moist rales over both pulmonary fields and the heart rate was 180 per minute. The abdomen was not distended. The extremities showed convulsive contractions during examination. During the seven hour stay in the hospital the patient became increasingly cyanotic despite oxygen and epinephrine hydrochloride therapy. It was noted that bleeding was pronounced at the sites of hypodermic puncture for the administration of medicaments and that large areas of ecchymosis developed around the injected sites. Slight bleeding was also noted from the vaginal and oral orifices. Convulsions occurred at one to two minute intervals. The convulsions ceased after about five hours and the temperature fell to 103 F. The heart rate increased in rapidity up to 240 per minute but remained regular. The respirations were noted to be Cheyne-Stokes in type. Two hours after entry to the hospital breathing ceased and artificial respiration was instituted. After the resumption of respiration constant bilateral twitching and spasms were noted. This was most decided in the lower extremities. Five hours after admission and seven hours after the onset of symptoms the patient showed great shock with pronounced collapse of the veins which rendered venipuncture difficult. Thirty minutes before death a surgical exposure of the right ankle vein was considered necessary for intravenous therapy. At that time an attempt was made to administer dextrose and saline solution with 10 per cent calcium gluconate. The patient was becoming more cyanotic and it was difficult to obtain the pulse beat. Artificial respiration was again instituted and after an intracardiac injection of epinephrine hydrochloride the patient was pronounced dead. Blood examination showed 80 per cent hemoglobin, 4.02 million red cells and 44,000 white cells with 36 per cent neutrophils, 61 per cent lymphocytes and 3 per cent eosinophils. The clinical picture of the patient was that of an allergic reaction which developed four hours after the injection and was characterized by convulsions, abdominal pain and vomiting with associated hemorrhagic phenomena., respiratory arrest, hyperthermia and death. The outcome of the event convulsions was recovered and outcome of other events was not reported. The cause of death was ascribed to anaphylactic shock secondary to the injection of influenza vaccine with air embolism as an immediate terminal contributory cause. A necropsy was performed about eleven hours after death which revealed the following: Heart: Air embolism was present in the right side of the heart and in the inferior vena cava; there were multiple epicardial hemorrhages. Thymus: Petechial subcapsular hemorrhages were present. Lungs: There were bilateral hypostatic congestion, emphysema of the right middle lobe and focal intra-alveolar hemorrhage. Adrenal: Decided bilateral atrophy was observed. Gastrointestinal Tract: Submucosal petechial hemorrhage of the esophagus was seen. Genitourinary Tract: There were submucosal petechial hemorrhages of the vagina. General: Multiple puncture wounds of the upper extremities and a recent phlebotomy wound of the right lower extremity were observed. Gross Observations: The body was that of the patient about 3 years of age and of normal height and weight. The left nostril showed abundant dried, blood tinged, foamy material. On the arms there were multiple hypodermic puncture marks in the region of the deltoid insertion on either side and small drops of fluid blood could be readily squeezed from the puncture wounds. The contiguous skin was ecchymotic. The left inguinal region showed recent venipuncture wounds with adjacent ecchymoses. The right longer extremity showed the presence of a recent transverse incision of the skin placed on the medial surface of the ankle and held together by interrupted sutures. The vagina showed the presence of two zones of submucosal hemorrhage just inside the fourchet. On incision of the fit it was noticed that the cut ends of the capillaries oozed fluid blood. When the thorax was opened both lungs lay free in the pleural sacs and did not appear hyperventilated. The right ventricle was greatly dilated and though its partly transparent wall multiple bubbles of air mixed with blood could be readily seen. With the circulation intact, several of the large venous pathways to the heart were exposed. The superior vena cava was natural. The left subclavian vain showed no evidence of air in its lumen. The inferior vena cava exposed along its entire length was seen to be distended and rounded and to contain a continuous column of frothy fluid blood along its entire length. The femoral vessels were exposed on both sides. Both femoral veins were collapsed. When the vessels were milked in a direction from the periphery to the trunk air bubbles were not recognized in either vessel; on milking the right iliac vein from the inguinal region in a cephalad direction, bubbles of air mixed with blood were seen. On exploration of the incised cutaneous wound of the right ankle at the site of phlebotomy, the underlying vein was readily identified and showed a ligature around its wall. Just proximal to the ligature a small nick corresponding to the site of puncture was readily identified. Anatomic Observations: Heart: The heart on removal weighed 909 Gm. The epicardial surfaces showed extensive Flame shaped hemorrhages both anteriorly and posteriorly. The right auricle and ventricle contained abundant fluid blood intimately mixed with numerous air bubbles of various sizes. The remainder of the examination of the heart revealed essentially normal structure. Lungs: The right lung weighed 120 Gm., the left 130 Gm. The posterior portions of both lobes of the left lung were dark red and on section cut with somewhat increased resistance to reveal a glistening, dark red, homogenous, nonconsolidated tissue, sections of which sank readily in water. The anterior portions of both lobes on this side were air containing and moderately congested and showed, in addition, scattered areas of circumscribed recent intra alveolar hemorrhage. The bronchi on this side showed intensely engorged mucosal surfaces having the appearance of red velvet. A culture taken from the main bronchus on this time grew a streptococcus of the alpha group and Staphylococcus aureus. The right lung had four lobes. The two lower lobes showed dark red circumscribed areas on their posterior portions, resembling those seen on the left side. In addition occasional lobules in the upper lobe appeared to be partly collapsed, being distinctly depressed below the adjacent pleural surfaces. One of the lobes also had a local area of emphysema on its anterior margin. The bronchi on this side resembled those of the left. The hilar nodes were natural. Thymus: The thymus was enlarged, weighed 30 Gm. and showed multiple subcapsular petechial hemorrhages. The cut surface was not noteworthy. Liver: The liver weighed 420 Gm. On section it revealed indistinctness of the lobular markings, the larger vessels oozing abundant blood. Spleen: The spleen weighed 55 Gm. and on section showed follicular hyperplasia. The pulp was firm and dark red. Adrenals: The adrenals were decidedly atrophic in appearance, the cortices being about 1 mm. in thickness. The medulla was similarly totally reduced on the side. Kidneys: The right kidney and left kidney each weighed 45 Gm. On section the cut surfaces were engorged. Uterus and Adnexa: The uterus and adnexa were natural for the age. Gastrointestinal Tract: The esophagus presented a few small submucosal hemorrhages in the distal half. The stomach contained about 2 ounces (59 cc.) of dark mucoid coagulum and showed normal mucosal surfaces. Lymphoid tissue: The Lymphoid tissues in the normal sites, more especially in the mesentery, were discretely enlarged and showed congested homogenous cut surfaces. Brain: The brain weighed 1,360 Gm and showed greatly engorged cerebral surfaces. On section the capillary systems in the gray and white matter were appreciably engorged. Microscopic examination showed sections of the lungs early acute interstitial inflammation in which mononuclear cells with fewer polymorphonuclear and only occasional eosinophils were seen. There was well defined intra alveolar and subpleural edema. In addition many of the air spaces showed recent intra-alveolar extravasation of red cells. Many colonies of bacteria were noted in the alveoli and bronchioles and were entirely devoid of any adjacent inflammatory cellular reaction. Occasional bronchioles showed the presence of their lumens of acidophilic albuminous exudate mixed with red cells. Sections of the heart muscle showed decided congestion of the vessels with scant areas of recent interstitial hemorrhage. There was well defined interstitial and subendocardial edema present. Sections of the spleen and lymph nodes displayed early follicular necrosis. The spleen on careful search failed to reveal any eosinophilic cells. The sections of the lymph node showed moderate eosinophilic cell infiltration. The adrenals manifested well defined cortical and medullary atrophy. The remainder of the organs revealed acute congestive change. The post mortem examination of the blood revealed 82.2 per cent hemoglobin, 4.75 million red cells and 7,400 white cells, with 26 per cent neutrophils, 74 per cent lymphocytes and a 0.87 color index. The author stated the fatal case of severe hemorrhagic allergic reaction occurred in the patient after influenza A and B vaccine was given subcutaneously in the prescribed dose. It was recommended that attempts should be made to further purify the various virus vaccines now becoming generally used so as to materially diminish the amount of reacting egg substances in the mediums of the marketed product. Since children appear more sensitive to egg protein than do adults greater precautions should be taken in this group of patients in the course of immunization with vaccines grown on egg mediums. The author concluded that simple precautions which have been outlined are observed should be little or no danger in continuing the vaccination of the civilian population with these agents which the accumulated evidence showed to have definite immunization value.