Dr.Jerin.K.John,Dr.Suma Balan(Ped Rheumatology),
Dr.Kumar Abhinav
(PedRheumatology),Dr.C.Jayakumar
(Pediatrics)
Three month-old female infant, the first child of a non-consanguineous marriage, born preterm at 35 weeks of gestation with a normal birth weight, presented with fever for three days. The fever was high-grade,
subsiding with acetaminophen
At 1.5 months of age, the infant had been admitted for culture-negative sepsis, presenting with fever, cough, rhinitis, and erythematous wheals with pustules.
Initial investigations revealed a
CRP of 99 mg/L, total leukocyte count of 31,380/mm³, platelet count of 1.4 lakhs/mm³, and a neutrophil-to-lymphocyte ratio of 66/25.
Urine routine microscopy showed 8–10 pus cells/hpf.
Ultrasound of the abdomen demonstrated focal calcifications in the upper pole of the right kidney and splenomegaly. She was treated with IV antibiotics for seven days.
Following this episode, she was referred for thrombocytopenia and splenomegaly. Further evaluations included a bone marrow biopsy, which showed normal hematopoietic elements. Lymphocyte subset analysis was normal. The immunoglobulin profile showed slightly lower levels of IgA, IgG, and IgM. Ophthalmologic evaluation was unremarkable, with no cherry red spots, corneal clouding, or retinopathy.
The current presentation involved recurrent daily fever spikes over one week, associated with bilateral erythematous indurated nodules on the lower limbs and a diffuse maculopapular rash over the trunk.
On examination, the ba was febrile with dysmorphic facies and organomegaly. Routine laboratory investigations revealed leukocytosis with a total count of 23,000/mm³, 63% neutrophils, hemoglobin of 9 g/dL, mildly low platelet counts, and a CRP of 84 mg/L. Peripheral smear showed normocytic normochromic anemia with leukocytosis and monocytosis.
Despite initiating empirical oral antibiotics, analgesics, and supportive measures, fever persisted, and the skin lesions worsened, particularly over the left groin.
A dermatology consultation and skin biopsy revealed neutrophilic panniculitis. Given the clinical picture of persistent fever, elevated inflammatory markers, dysmorphic facies, organomegaly, and skin biopsy findings, an autoinflammatory syndrome was suspected.
Advanced investigations included NBT and DHR tests to rule out immunodeficiency, interferon signature testing to exclude interferonopathies, and a CT brain to evaluate calcifications, which showed normal findings. Blood cultures were sterile, and tympanometry results were normal. Ophthalmologic evaluation was repeated, and VEP was suggested.
The infant was started on 1 mg/kg corticosteroids, which led to the rapid resolution of fever and significant improvement in the skin lesions.
Differential Diagnosis
Chronic Infantile Neurological, Cutaneous, and Articular Syndrome (CINCA)
Periodic Fever Syndromes (e.g., Familial Mediterranean Fever, Hyper IgD Syndrome
Majeed Syndrome
Pyogenic Sterile Arthritis, Pyoderma Gangrenosum, and Acne (PAPA Syndrome)
Secondary causes of neutrophilic panniculitis (e.g., infections, malignancies
Primary Immunodeficiencies (e.g., Chronic Granulomatous Disease, Leukocyte Adhesion Deficiency)
Discussion
Autoinflammatory syndromes are a group of disorders characterized recurrent episodes of fever and systemic inflammation in the absence of infection, malignancy, or autoimmune pathology. These syndromes involve innate immune system dysregulation and are often associated with characteristic clinical and laboratory findings.
This case highlights the diagnostic challenges in identifying autoinflammatory syndromes in neonates and infants, where clinical presentations overlap significantly with infectious and immunodeficiency disorders. The recurrent fever, high inflammatory markers, skin lesions suggestive of neutrophilic panniculitis, and lack of response to antibiotics steered the diagnosis toward an autoinflammatory disorder.
Neutrophilic panniculitis is a hallmark feature in certain autoinflammatory conditions, such as Majeed syndrome, but can also occur in other conditions like periodic fever syndromes or interferonopathies. The exclusion of immunodeficiency through normal lymphocyte subset analysis, NBT and DHR tests, and normal immunoglobulin profiles was crucial in ruling out alternative diagnoses. Similarly, normal imaging findings and negative infectious workup ruled out secondary causes.
The dramatic response to corticosteroids further supports the diagnosis of an autoinflammatory syndrome, emphasizing the importance of timely immunomodulatory therapy to prevent complications. Early intervention not only resolves systemic inflammation but also prevents long-term sequelae, including organ damage and growth failure.
Take-Home Message
Autoinflammatory syndromes should be considered in infants with recurrent fever, high inflammatory markers, and cutaneous manifestations such as neutrophilic panniculitis. A systematic approach involving multidisciplinary teams is essential for the early diagnosis and management of these rare conditions.
Exclusion of infectious and immunodeficiency causes is vital before initiating immunomodulatory therapy.
Corticosteroids are effective in controlling inflammation and can serve as the first line of treatment in suspected autoinflammatory syndromes.
Prompt recognition and treatment are key to preventing complications and ensuring favorable outcomes.