Limits...
Interleukin-1 receptor antagonist deficiency with a novel mutation; late onset and successful treatment with canakinumab: a case report.

Ulusoy E, Karaca NE, El-Shanti H, Kilicoglu E, Aksu G, Kutukculer N - J Med Case Rep (2015)

Bottom Line: Our patient did not experience further cutaneous lesions or arthritis.Her post-treatment inflammatory markers were normal; she gained weight; and she was able to walk independently.It is possible that the mutation in our patient was a founder mutation that may lead to diagnosis of additional cases in Turkey.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey. ezgiulusoy13@hotmail.com.

ABSTRACT

Introduction: Interleukin-1 receptor antagonist deficiency is a rare autoinflammatory disease involving neonatal onset of pustulosis, periostitis, and sterile osteomyelitis. The underlying genetic abnormality involves a recessive mutation in IL1RN, which encodes interleukin-1 receptor antagonist. In this case report, we describe a case of a 12-year-old Turkish girl who initially was presented at 1 year of age, older than previously reported children with interleukin-1 receptor antagonist deficiency, and with a novel mutation, p.R26X, in ILR1N.

Case presentation: Our patient developed pustular cutaneous lesions at 1 year of age. At the age of 12 years, she was hospitalized for arthralgia of her knees, elbows, and ankles and arthritis of the left knee, with simultaneous pustular cutaneous lesions. She was admitted to the intensive care unit because of septicemia and respiratory insufficiency during follow-up. A skin biopsy of hyperpigmented lesions demonstrated neutrophil infiltration in the epidermis and subepidermal pustular dermatosis. Interleukin-1 receptor antagonist deficiency was suspected, and genetic analysis revealed a homozygous mutation (p.R26X) in IL1RN, which led to a diagnosis of interleukin-1 receptor antagonist deficiency. Treatment with canakinumab (recombinant human anti-human interleukin-1β monoclonal antibody) 150 mg subcutaneously once every 6 weeks was initiated. Our patient did not experience further cutaneous lesions or arthritis. Her post-treatment inflammatory markers were normal; she gained weight; and she was able to walk independently.

Conclusions: In this case report, we describe a patient with interleukin-1 receptor antagonist deficiency who responded excellently to canakinumab treatment. We believe more awareness is warranted for interleukin-1 receptor antagonist deficiency in children. It is possible that the mutation in our patient was a founder mutation that may lead to diagnosis of additional cases in Turkey.

No MeSH data available.


Related in: MedlinePlus

a Inguinal and pubic hyperpigmented scar lesions. b Paronychia of the toes
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4495801&req=5

Fig1: a Inguinal and pubic hyperpigmented scar lesions. b Paronychia of the toes

Mentions: A hyperpigmented scar lesion on the right side of the face; bilateral inguinal, paraumbilical hyperpigmented scar lesions; and paronychia of the thumbs were noted on admission (Fig. 1). Additionally, the patient had contracture of the left knee limiting her motion, episcleritis, and failure to thrive [25kg (below third percentile), 132cm (below third percentile)]. The results of her laboratory studies revealed iron deficiency anemia, hypergammaglobulinemia, and elevated acute-phase reactants (red blood cell count 4.2 million/mm3, hemoglobin 9.1g/dl, hematocrit 27.8%, mean corpuscular volume 81fl, thrombocytes 254,000/mm3, immunoglobulin G (IgG) 1760mg/dl, IgM 186mg/dl, IgA 195mg/dl, C-reactive protein 6.5mg/dl, erythrocyte sedimentation rate 100mm/hr, and serum amyloid A 123mg/L). Total IgE level, eosinophil count, lymphocyte subset levels, and the oxidative burst activity of granulocytes were normal. Autoantibodies (anti-nuclear antibody, anti-neutrophilic cytoplasmic antibody, and rheumatic factor) were negative. She was evaluated for tuberculosis and was found to have two bacillus Calmette-Guérin scars, a 12mm tuberculin response, and a negative QuantiFERON® assay result (QIAGEN, Chadstone, Australia). Serologic investigations yielded negative results for cytomegalovirus, Epstein-Barr virus, hepatitis B and C viruses, syphilis, and HIV. Her blood and urine cultures were negative for bacteria. Splenomegaly was detected by abdominal ultrasonography. Skin biopsy of hyperpigmented lesions demonstrated neutrophil infiltration in epidermis and subepidermal pustular dermatosis. The results of chest radiography and skeletal surveys were normal.Fig. 1


Interleukin-1 receptor antagonist deficiency with a novel mutation; late onset and successful treatment with canakinumab: a case report.

Ulusoy E, Karaca NE, El-Shanti H, Kilicoglu E, Aksu G, Kutukculer N - J Med Case Rep (2015)

a Inguinal and pubic hyperpigmented scar lesions. b Paronychia of the toes
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4495801&req=5

Fig1: a Inguinal and pubic hyperpigmented scar lesions. b Paronychia of the toes
Mentions: A hyperpigmented scar lesion on the right side of the face; bilateral inguinal, paraumbilical hyperpigmented scar lesions; and paronychia of the thumbs were noted on admission (Fig. 1). Additionally, the patient had contracture of the left knee limiting her motion, episcleritis, and failure to thrive [25kg (below third percentile), 132cm (below third percentile)]. The results of her laboratory studies revealed iron deficiency anemia, hypergammaglobulinemia, and elevated acute-phase reactants (red blood cell count 4.2 million/mm3, hemoglobin 9.1g/dl, hematocrit 27.8%, mean corpuscular volume 81fl, thrombocytes 254,000/mm3, immunoglobulin G (IgG) 1760mg/dl, IgM 186mg/dl, IgA 195mg/dl, C-reactive protein 6.5mg/dl, erythrocyte sedimentation rate 100mm/hr, and serum amyloid A 123mg/L). Total IgE level, eosinophil count, lymphocyte subset levels, and the oxidative burst activity of granulocytes were normal. Autoantibodies (anti-nuclear antibody, anti-neutrophilic cytoplasmic antibody, and rheumatic factor) were negative. She was evaluated for tuberculosis and was found to have two bacillus Calmette-Guérin scars, a 12mm tuberculin response, and a negative QuantiFERON® assay result (QIAGEN, Chadstone, Australia). Serologic investigations yielded negative results for cytomegalovirus, Epstein-Barr virus, hepatitis B and C viruses, syphilis, and HIV. Her blood and urine cultures were negative for bacteria. Splenomegaly was detected by abdominal ultrasonography. Skin biopsy of hyperpigmented lesions demonstrated neutrophil infiltration in epidermis and subepidermal pustular dermatosis. The results of chest radiography and skeletal surveys were normal.Fig. 1

Bottom Line: Our patient did not experience further cutaneous lesions or arthritis.Her post-treatment inflammatory markers were normal; she gained weight; and she was able to walk independently.It is possible that the mutation in our patient was a founder mutation that may lead to diagnosis of additional cases in Turkey.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey. ezgiulusoy13@hotmail.com.

ABSTRACT

Introduction: Interleukin-1 receptor antagonist deficiency is a rare autoinflammatory disease involving neonatal onset of pustulosis, periostitis, and sterile osteomyelitis. The underlying genetic abnormality involves a recessive mutation in IL1RN, which encodes interleukin-1 receptor antagonist. In this case report, we describe a case of a 12-year-old Turkish girl who initially was presented at 1 year of age, older than previously reported children with interleukin-1 receptor antagonist deficiency, and with a novel mutation, p.R26X, in ILR1N.

Case presentation: Our patient developed pustular cutaneous lesions at 1 year of age. At the age of 12 years, she was hospitalized for arthralgia of her knees, elbows, and ankles and arthritis of the left knee, with simultaneous pustular cutaneous lesions. She was admitted to the intensive care unit because of septicemia and respiratory insufficiency during follow-up. A skin biopsy of hyperpigmented lesions demonstrated neutrophil infiltration in the epidermis and subepidermal pustular dermatosis. Interleukin-1 receptor antagonist deficiency was suspected, and genetic analysis revealed a homozygous mutation (p.R26X) in IL1RN, which led to a diagnosis of interleukin-1 receptor antagonist deficiency. Treatment with canakinumab (recombinant human anti-human interleukin-1β monoclonal antibody) 150 mg subcutaneously once every 6 weeks was initiated. Our patient did not experience further cutaneous lesions or arthritis. Her post-treatment inflammatory markers were normal; she gained weight; and she was able to walk independently.

Conclusions: In this case report, we describe a patient with interleukin-1 receptor antagonist deficiency who responded excellently to canakinumab treatment. We believe more awareness is warranted for interleukin-1 receptor antagonist deficiency in children. It is possible that the mutation in our patient was a founder mutation that may lead to diagnosis of additional cases in Turkey.

No MeSH data available.


Related in: MedlinePlus