Hyperimmunoglobulin D Syndrome Presenting with Volvulus Due to Abdominal Fibro-Inflammatory Bands

Hyperimmunoglobulin D syndrome (HIDS) is an autoinflammatory disease caused by autosomal recessive mutations in the MVK gene, which encodes an enzyme called mevalonate kinase.^1,2 The disease is characterized by recurrent fever, lymphadenopathy, gastrointestinal (GI) manifestations, hepatosplenomegaly, skin rash, and mucosal ulcers.³ The disease usually starts in the first year of life. According to the largest pediatric HIDS cohort, the median flare frequency was 12 episodes per year, lasting approximately 4 days.³ These episodes might be provoked by specific triggers such as vaccination, stress, and infection.³ Patients are generally well between attacks but about 10%-20% of the patients had constitutional symptoms such as fatigue between fever episodes.³

Gastrointestinal symptoms are commonly seen in HIDS patients, such as abdominal pain, diarrhea, and vomiting. Herein we report a patient presented with volvulus due to abdominal fibro-inflammatory bands. After a detailed evaluation, the patient was diagnosed with HIDS which caused these bands probably due to recurrent sterile peritonitis.

A 3-year-old boy presented to our emergency department with 2 days of fever, abdominal pain, and projectile bilious vomiting. The physical examination revealed bilateral cervical lymphadenopathy, abdominal distension, rebound tenderness, and decreased bowel sounds. His blood tests are given in Table 1. Abdomen x-ray showed air-fluid levels with dilated intestines. An abdominal computed tomography was performed which was compatible with small intestine obstruction due to midgut volvulus without any pathological lymph nodes. He was started on wide-spectrum antibiotics. The pediatric surgery department performed a laparotomy and dissected the fibrotic bands causing the mechanical obstruction (Figure 1). After the operation, the patient had abdominal pain and high acute phase reactants despite broadening the antibiotics. The infectious screening was unremarkable including possible viral and bacterial pathogens and tuberculosis screening. The pediatric gastroenterology department evaluated the patient for recurrent GI symptoms and excluded other etiologies such as inflammatory bowel disease, etc. A biopsy taken during the dissection of the fibro-inflammatory bands showed fibrosis, congestion, and active chronic inflammation consisting of neutrophils and lymphocytes without any amyloid deposition. The previous history of the patient revealed that he had recurrent fever attacks every 30-45 days lasting 4-6 days accompanied by abdominal pain, oral aphthous, diarrhea, cervical lymphadenopathy without rash, and tonsillitis. He was the second child of a first-degree consanguineous marriage. His sister had similar recurrent fever episodes lasting 3-6 days with abdominal pain, oral aphthous, and diarrhea. There was no other history of rheumatic diseases in the family history.

Table 1.

Laboratory Findings of the Patient

Hemoglobin	12 g/dL
White blood cells	17 850/mm3
Platelets	629 000/mm3
Erythrocyte sedimentation rate	15 mm/h
C-reactive protein	136.4 g/L
Alanine aminotransferase	11 U/L
Aspartate transaminase	21 U/L
Blood urine nitrogen	38 mg/dL
Creatinine	0.41 mg/dL
Urinalysis	Unremarkable

Figure 1.

(A) Strangulation and dilatation of small intestine; (B) Fibrous band causing midgut volvulus.

After excluding other causes with the patient’s history, infectious screening, and immunological evaluation, 1 mg/kg/day of methylprednisolone was started together with colchicum for possible autoinflammatory disease. Eventually, the abdominal pain decreased together with the normalization of the acute phase reactants. The patient was discharged with a steroid tapering plan. We performed a next-generation screening panel including autoinflammatory diseases (NLRP3, MVK, TNFRSF1A, NLRP12, PSTPIP1, NOD2, ELANE2, IL1RN, MEFV, LPIN2, ADA2, TNFRSF11A, CARD14, PSMB8, IL10RA, IL10RB, and NLRP7) revealing that the patient had homozygous V377I mutation on MVK gene (most common pathogenic variant causing HIDS⁴) and heterozygous M694V mutation on MEFV gene (most common pathogenic variant causing familial Mediterranean fever (FMF)⁵). His attacks continued after the cessation of steroids, and we started canakinumab with the diagnosis of HIDS. He is now attack-free with canakinumab treatment. Both written and verbal consent have been obtained from the parents.

Hyperimmunoglobulin D syndrome is an autoinflammatory disease characterized by recurrent fever episodes, rash, lymphadenopathy (mostly cervical), and GI findings and in severe forms neurological impairments and ocular and auditory abnormalities.^3,6-8 It is caused by autosomal recessive mutations in the MVK gene.^1,2 Although it is an autosomal recessive disease, our patient and his sister were diagnosed with HIDS as their parents were first-degree relatives. The onset was very early in life, with a median age of 0.5 years.³ According to the largest patient series, GI symptoms were seen in 98% of the patients.³ The most common GI symptoms were abdominal pain (88%), diarrhea (84%), and vomiting (69%). Abdominal adhesions have been reported in 4 patients in a registry of 114 patients.³ In another registry of 103 patients, 10 of them had adhesions; among those, 6 of them have been found during laparotomy done for suspected appendicitis.⁹ Abdominal adhesions and spontaneous small-bowel obstruction were reported in 2%-3% of FMF patients in different series as well.^10,11 Although FMF is the most common autoinflammatory disease, especially in Turkey, patients who have additional findings which are not compatible with FMF should be evaluated further. Recently, a patient was diagnosed with HIDS when she started to have cervical lymphadenopathy, maculopapular rash, and diarrhea during her attacks and was initially diagnosed as FMF due to recurrent episodes of fever and abdominal pain only.¹²

Our patient did not have any operations before but presented with an attack together with midgut volvulus. Up to our knowledge, this is the first HIDS case presented with volvulus and fibro-inflammatory bands, probably due to repeated sterile peritonitis. One can speculate that having heterozygous M694V mutation together with HIDS might worsen the presentation and the severity of the sterile peritonitis which eventually resulted in the formation of fibro-inflammatory bands. Dissecting the bands did not cure the abdominal pain which persisted until steroid treatment was given with which the attack subsided. The patient had flares during the steroid tapering plan; thus, we started anti-interlekin 1 treatment as recommended in the literature.^13-15

Although other more common etiologies should be investigated in a patient presenting with volvulus, HIDS should also be kept in mind if the patient has recurrent fever episodes, abdominal pain, diarrhea, and lymphadenopathies.