Two Siblings with Recurrent Fevers

Recurrent fevers are a diagnostic challenge in Pediatrics which requires a systematic structured approach since differential diagnosis is vast.

The authors present the case of a 14 year-old caucasian girl, with no relevant family history. She presented with recurrent fevers since the first year of life, with a duration of 3-7 days at variable intervals (1-6 months). Accompanying symptoms included oral ulcers, cervical lymphadenopathies and arthralgia. She was assyntompatic between attacks, with normal growth and development. After excluding infectious, neoplastic and autoimmune causes, a PFAPA diagnosis was assumed. The patient was treated with a 1-2 day course of prednisolone with favorable response.

At age 12 she presented with genital ulcers during a febrile episode and was referred to our Pediatric Rheumatology Unit. During our evaluation, she complained also of macular rash and abdominal pain with ocasional diarrhea during the episodes.

Investigations during attacks revealed increased inflammatory markers (IM), IgA, IgD and urinary mevalonic acid. Between attacks IM are normal, with mild anemia.

Genetics identified MVK variants c.79-2A>G and c.1129G>A in heterozygosity, which confirmed HyperIgD syndrome (HIDS) diagnosis. She´s receiving NSAIDs and rare short courses of steroids during attacks with adequate control.

Her 9 year-old brother was then brought to our attention with a history of recurrent fevers and rash since the first year of life. Currently, he presents with 6-7 episodes/year, 5-6 days duration, associated with painful cervical lymphadenopathies and occasional diarrhea and artralgia. His genetic study identified the same MVK variants, confirming a HIDS diagnosis.

HIDS is an autosomal recessive autoinflamatory syndrome caused by mutations in the MVK gene. Its presentation is very variable but usually early onset, and can be confused with PFAPA.

Diagnosis is paramount for its therapeutic implications, monitoring for secondary amyloidosis and to detect other cases within the same family, such as in this case.