Acute Hemorrhagic edema of infancy

Acute Hemorrhagic edema of infancy is a rare and benign leukocytoclassic vasculitis that is more common in children aged 4 to 24 months. The prevalence of this disease is higher in boys and it often occurs in winter. The exact cause is unknown, but from a pathophysiological point of view, it is a type of vasculitis associated with immune complexes. Staphylococcus, Streptococcus, Adenoviruses, Escherichia coli and Mycobacterium are also thought to be involved. Clinical features include sudden onset of fever, purpuric skin lesions with erythema and edema involvement, from millimeters to several centimeters in diameter, sometimes targeted with pale, bold rings. It occurs mostly on face, ear lobes, and lower extremities. In the majority of cases, it is limited to the skin and other organs are rarely involved (1, 2). The disease was first reported in 1913 (3, 4). Of course, it was considered as Henoch-Schonlein purpura for a long time and later has been known as a completely independent disease. So far, 300 cases have been reported under different names in the world: Seidlmayer purpura, Finkelstein disease, rosette form purpura, medallion-like purpura, infantile post-infectious iris-like purpura and edema3 (5-7). Introduced case is an 8-month-old infant who was referred with skin lesions to the pediatric ward of Amir Al-Momenin Hospital in Zabol Case Presentation: The patient was an 8-month-old boy with sudden and progressive ecchymotic skin lesions in the lower limbs and ears, as well as involvement and swelling of the genitalia, in February 2021 admitted in pediatric ward. (Figures 1-3). At the beginning of hospitalization, the patient had a rise in severity of lesions in the form of ecchymosis, petechiae and palpable painful annular purpura with a diameter between 1-5 cm. History and physical examination of the infant revealed no previous Antibiotic or vaccination in recent few weeks. His mother reported a history of mild upper respiratory tract infection with a low grade fever, Rhinorrhea and dry cough which had been resolved without any special treatment. The infant had a good general condition, and his respiratory rate, heart rate, blood pressure and temperature were within the normal range for the age and sex. Touching and moving of involved areas was slightly painful. There is no evidence of mucosal surfaces such as the mouth and nose or internal organ involvement. The infant remained completely happy throughout the hospital stay. In laboratory tests: White Blood Cells 19500/ml (Neutrophil 44%, Lymphocyte 53%, Monocyte 1% and Eosinophil 1%), Hemoglobin 10 g /dl, Platelet 328000/ml, ESR 45 mm/h, CRP 1+ and coagulation profile and liver enzimes were normal. In addition, Serum Complement levels (c3, c4) and IgA were normal. ASO and AntiNuclear Antibody titers were negative. Serum electrolytes and creatinine were normal. Abnormal urine analysis and fecal examination were not observed. Blood and urine cultures were negative. Abdomino pelvic Ultrasound and color Doppler Ultrasound of testis and scrotum were also normal. No skin biopsy was performed due to its benign process and rapid recovery. During the 10-day hospitalization period, the patient had a good general condition. Blood pressure and temperature remained normal. The skin disorder completely disappeared within 6 to 10 days and the patient was discharged in a good general condition. Discussion: Acute Hemorrhagic Edema of Infancy (AHEI) is a benign cutaneous vasculitis. Despite a history of upper respiratory tract infection, urinary tract infection, and vaccination in 75% of cases, the etiology of the disease remains unclear (8-10). In the Behmanesh study in 2011, two cases of AHEI were reported, both boys aged 9 and 14 months. In one case, history of upper respiratory infection 14 days earlier with leukocytosis, ESR: 85, and CRP3 + were seen. Other laboratory tests were normal in both. Due to the benign clinical course, no biopsy was performed and recovery was achieved within 10-14 days. (11) In a 2019 study by Elena Carboni et al, An 11-month-old girl with fever and elliptical purpuric skin lesions on the face and limbs. She had a history of bilateral conjunctivitis and gastroenteritis one week before admission. She had good general condition and stable vital signs. Leukocytosis, Eosinophilia, Thrombocytosis, along with increased ESR and CRP, were the positive laboratory findings. Skin biopsy showed leukocytoclastic vasculitis of small cutaneous vessels associated with perivascular neutrophil infiltration. (12). In the present case, previous history of respiratory infection, leukocytosis, lymphocytosis and increased ESR and CRP were the abnormal findings. Krause and colleagues described five cases of AHEI and suggested some diagnostic criteria: age less than two years, ecchymotic or purpuric lesions with facial edema, auricles of ears and limbs with or without mucosal involvement, absence systemic disease or visceral involvement and spontaneous recovery within a few days or weeks (6). And in this case, also, there were all the above criteria. The main feature of the disease is a obvious conflict between the acute skin symptoms and the patient's very good general condition. (13) In García-Muro study in 2019, a happy 2-month-old infant with a history of recent upper respiratory infection had maculopapular and purpuric lesions in face and limbs with swelling of the face and ears. and also palm and foot involvement. Mild leukocytosis, lymphocytosis, thrombocytosis with negative findings for other laboratory test and rhinovirus negative virology test. With conservative treatment, the skin involvement subsided within 6 days. In the present study, leukocytosis and lymphocytosis were also seen, but there was no thrombocytosis and no virological test was performed. (14) In another study, the disease was clinically characterized by fever, purpuric skin lesions, and edema. Purpuric lesions appeared on the face, auricles and limbs, with edema of the scalp, limbs and genitalia without trunk involvement (15). our study had all the conditions mentioned. Diagnosis is based on clinical signs. CRP, ESR is usually normal or slightly increased. There may be eosinophilia, leukocytosis, and thrombocytosis, which may be due to an acute inflammatory process; the complement level is normal (16). Other tests such as blood coagulation tests (INR, PT, PTT), UA, liver and kidney function tests, VDRL, ANA, IgM, IgA, ASO are normal (17). In this patient, CRP: +2 and ESR were increased and leukocytosis with lymphocytosis was reported in CBC and other tests were normal. Histopathologic examination has been done seldomly and its results vary from a leukocytoclastic vasculitis with or without fibrinoid necrosis to more nonspecific findings such as perivascular lymphohistocytic infiltration with extravasation of Red Blood Cells. The differential diagnoses of this disease are Henoch-Schonlein purpura, Sweet syndrome, erythema multiforme, Kawasaki disease, meningococcemia, urticarial vasculitis, child abuse and drug-induced vasculitis (4). An important differential diagnosis of this disease is Henoch-Schonlein purpura (HSP). Both of them are leukocytoclassic vasculitis and appear in winter (18). There are a number of distinctions between them: onset of HSP is about 2-8 years, but AHEI age of onset is 2-24 months (19). Clinical manifestations of HSP include skin rash, arthritis, abdominal pain (sometimes gastrointestinal bleeding), and renal involvement (20). These manifestations are rare in AHEI. The skin manifestation of HSP consists of urticarial lesions, erythematous and papular rashes, petechiae and purpura or subcutaneous edema that characteristically involve the lower limbs and buttocks (21). However, in AHEI purpura is on face and larger ecchymoses are seen on limbs, which can be associated with severe and extensive edema (22). In this patient, in the absence of abnormal urinalysis test and gastrointestinal and joint symptoms, HSP has been excluded. Absence of thrombocytopenia and purpuric lesions are against to the diagnosis of serum sickness. Sweet syndrome is rare in children, often accompanied by osteomyelitis, joint pain, musculoskeletal pain, and is often secondary to malignancy (1). The present patient was not in a critical condition. Rapid recovery, negative Anti-Nuclear Anti Body, and normal levels of complement make rheumatic diseases such as lupus erythematosus unlikely. High Erythrocyte Sedimentation Rate is against to diagnosis of drug reactions. Systemic infections such as meningococcal disease are ruled out due to well-being afebrile patient. No particular treatment is needed for AHEI. Spontaneous recovery occurs in 2 to 3 weeks (17). conclusion: Acute hemorrhagic edema of infancy (AHEI) is a rare leukocytoclastic vasculitis with skin involvement characterized by purpuric lesions and edema, usually involving male infants 4 to 24 months of age. Most cases are associated with a recent history of viral or bacterial infection. The diagnosis is completely clinical, has a self-limiting process and improves without special treatment and has a good prognosis. Therefore, strong clinical suspicion during the patient's examination, in the absence of evidence of other serious differential diagnoses, will reduce the need for invasive and expensive tests. .