A punch biopsy of one of the lesions showed a superficial and deep mixed inflammatory cell infiltrate, including neutrophils and eosinophils. There was also vasculitis, karyorrhexis and extravasated red blood cells. The findings are those of leukocytoclastic vasculitis, suggestive of acute hemorrhagic edema of infancy. Direct immunofluorescence was positive for IgM, C3, and fibrinogen, but negative for IgA.
Acute hemorrhagic edema of infancy (AHEI), also known as Finkelstein disease, is form of leukocytoclastic vasculitis that occurs in infants and toddlers aged between4 months and 3 years.
The lesions start as petechiae or edematous, erythematous to violaceous nodules that later coalesce and form “cockade”-like plaques with a central clearing on the face and extremities.Gastrointestinal, renal, and joint involvement are rare.1 AHEI follows a benign course with resolution of the lesions and symptoms within days to weeks. The etiology of this condition is not known but infection triggers have been reported including coronavirus infections, coxsackie virus infections, Escherichia coli urinary tract infections, herpes simplex virus stomatitis, and pneumococcal bacteremia.2,3 Our patient had a prior history of pneumococcal pneumonia and metapneumovirus infection. MMR vaccine also has been reported as a possible trigger, as well as some medications.
Laboratory results are usually normal, but some patients may have elevated inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), as noted in our patient, and leukocytosis, thrombocytosis, and eosinophilia. Microscopic analysis demonstrates leukocytoclastic vasculitis of small vessels with associated karyorrhexis and extravasated red blood cells.
The differential diagnosis includes other vasculitic conditions, primarily Henoch-Schönlein purpura (HSP). Patients with HSP tend to be older in age and the lesions described as palpable purpura commonly affect the lower extremities and buttocks. These patients can present with abdominal pain and arthritis; renal compromise also can occur. Direct immunofluorescence can commonly be positive for IgA, which was negative in our patient.
AHEI and HSP are considered different entities, but both present with leukocytoclastic vasculitis.1 Another condition to consider in patients with fever, rash, and edema is Kawasaki disease, also a form of vasculitis, that affects small- and medium-size muscular vessels with predilection for the coronary arteries. Patients with Kawasaki disease present with fever (usually longer than 5 days), facial and extremity edema (similar to AHEI), skin lesions (which may have multiple presentations, the most common being macular, papular and erythematous, and urticarial eruptions), but also lymphadenopathy and conjunctivitis. These patients appear sicker than children with AHEI. Their laboratory results show leukocytosis, thrombocytosis or thrombocytopenia, elevated inflammatory markers, and sterile pyuria.4
Patients with erythema nodosum present with tender erythematous nodules, which can look like early AHEI lesions. The most common location is the lower extremities, but in children erythema nodosum can occur on the face, trunk, and arms. The lesions can occur secondary to infections such as streptococcus, mycoplasma, tuberculosis, coccidioidomycosis, and sarcoidosis, as well as to malignancy or medications. These patients do not appear sick, are not febrile, and are rarely seen under 2 years of age.5
Acute febrile neutrophilic dermatosis – Sweets’ syndrome – also should be considered in a patient with tender nodules, fever, and leukocytosis. The skin lesions in Sweets’ syndrome, compared with those in AHEI, are painful and can present as papules, nodules, and bullae on the face and extremities. A prior history of an upper respiratory infection is commonly described in children with Sweets’ syndrome. These patients present with fever, which may start days to weeks prior to the lesions starting. Children with Sweets’ syndrome also can have conjunctivitis, myalgias, polyarthritis, and in severe cases septic shock and multiorgan dysfunction. Sweets’ syndrome can be seen in patients with inflammatory bowel disease, systemic lupus erythematosus, chronic multifocal osteomyelitis, and malignancy; it also may be induced by certain medications.6
As mentioned above, the course of AHEI is benign, and the condition resolves within days to weeks. Treatment is supportive.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She had no relevant financial disclosures. Email Dr. Matiz at firstname.lastname@example.org.