Information on AIPDS
Basic details
Name: Autoinflammation, panniculitis, and dermatosis syndrome | Acronym: AIPDS
Alt. names: otulipenia | ORAS | OTULIN-related autoinflammatory syndrome
Gene: OTULIN | MOI: Autosomal recessive | Mechanism of action: Loss of Function
No. of cases in DB: 9 | First reported in: 2016
Last updated on: 2023-12-01 13:26:49 by Andrés Caballero-Oteyza
Description
Early-onset systemic autoinflammatory condition in which the majority of individuals presented with episodes of unexplained fevers, elevated CRP levels, leukocytosis and neutrophilia, but also panniculitis and lipodystrophy, rashes and neutrophilic infiltration of the skin, and arthritis/arthralgias. Patients often exhibit no overt evidence of immunodeficiency.
Management
All reported individuals responded positively to steroids to some extent. However, these were often not durable responses, while all patients who were trialed on TNF inhibition showed at least moderate, if not robustly, positive responses. By comparison, anakinra, colchicine, ruxolitinib and methotrexate elicited only partial clinical responses in one individual at most (PMID: 27523608, 27559085, 35170849)
9 reported cases added to GenIA
| SubjectID | Sex | Fam.ID | AD | AFM | Validity | Country | Population | Reference & Pub.code |
|---|---|---|---|---|---|---|---|---|
104554 |
M | 215551 |
11 | 0 | Pakistan | Pakistani | PMID:27523608 [Fam.1:V.2(V:2)]; PMID:27559085 [Fam.1:V.2(P1)]; PMID:35587511 [Fam.G:II.2(4)]; PMID:34797715 [P1]; PMID:38914362 [Fam.A:V.2(023)] | |
| 104568 |
F | 215551 |
1 | 0 | Pakistan | Pakistani | PMID:27523608 [Fam.1:IV.3(IV:3)]; PMID:32231246 [IV:3(IV.3)]; PMID:27559085 [Fam.1:IV.1(P4)]; PMID:38914362 [Fam.A:V.6(027)] | |
| 104570 |
F | 215551 |
5 | 0 | Pakistan | Pakistani | PMID:27523608 [Fam.1:IV.4(IV:4)]; PMID:27559085 [Fam.1:IV.3(NA)]; PMID:38914362 [Fam.A:V.7(028)] | |
| 104575 |
F | 215552 |
4 | 0 | Turkey | Turkish | PMID:27559085 [Fam.2:II.1(P2)]; PMID:35587511 [Fam.I:II.2(4)]; PMID:34797715 [P2]; PMID:38914362 [Fam.B:II.1(035)] | |
| 104580 |
F | 215553 |
11 | 0 | Turkey | Turkish | PMID:27559085 [Fam.3:II.1(P3)]; PMID:35587511 [Fam.H:II.1(3)]; PMID:34797715 [P3]; PMID:38914362 [Fam.C:II.1(039)] | |
| 104583 |
F | 215554 |
12 | 0 | Israel | Arab | PMID:30804083 [Patient(III.2)]; PMID:35587511 [Fam.K:II.2(4)]; PMID:38914362 [Fam.D:IV.2(049)] | |
| 104592 |
F | 215555 |
1 | 0 | Iran | Iranian | PMID:30796585 [Patient(V.3)]; PMID:35587511 [Fam.J:II.3(5)]; PMID:38914362 [Fam.E:V.3(065)] | |
| 104612 |
M | 215557 |
7 | 1 | Germany | Greek | PMID:35170849 [Patient(II.2)]; PMID:38914362 [Fam.F:II.2(069)] | |
| 105135 |
F | 215649 |
1 | 0 | Morocco | Moroccan | PMID:38914362 [Fam.M:II.1(107)] |
AD: Age at genetic diagnosis; AFM: age at first manifestation; PMID: PubMed ID; GRID: GenIA reference ID (ref. not in PubMed).
Summary of clinical findings
[Considering only Definitive and Possible cases]
| Rank | Clinical term | Present | Absent | Unreported |
|---|---|---|---|---|
| 1 | Systemic autoinflammation |
9 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 2 | Elevated C-reactive protein |
9 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 3 | Leukocytosis |
8 (88.9%) | 0 (0.0%) | 1 (11.1%) |
| 4 | Panniculitis |
7 (77.8%) | 0 (0.0%) | 2 (22.2%) |
| 5 | Failure to thrive |
6 (66.7%) | 0 (0.0%) | 3 (33.3%) |
| 6 | Fever |
5 (55.6%) | 0 (0.0%) | 4 (44.4%) |
| 7 | Abnormal lymphoproliferation |
5 (55.6%) | 2 (22.2%) | 2 (22.2%) |
| 8 | Neutrophilia |
5 (55.6%) | 0 (0.0%) | 4 (44.4%) |
| 9 | Skin rash |
5 (55.6%) | 0 (0.0%) | 4 (44.4%) |
| 10 | Neutrophilic infiltration of the skin |
4 (44.4%) | 0 (0.0%) | 5 (55.6%) |
| 11 | Arthralgia |
4 (44.4%) | 0 (0.0%) | 5 (55.6%) |
| 12 | Hepatopathy |
4 (44.4%) | 2 (22.2%) | 3 (33.3%) |
| 13 | Recurrent fevers |
4 (44.4%) | 0 (0.0%) | 5 (55.6%) |
| 14 | Increased IgA levels |
4 (44.4%) | 0 (0.0%) | 5 (55.6%) |
| 15 | (unusual) Respiratory tract infection |
3 (33.3%) | 2 (22.2%) | 4 (44.4%) |
| 16 | Skin nodule |
3 (33.3%) | 0 (0.0%) | 6 (66.7%) |
| 17 | Lung disease |
3 (33.3%) | 2 (22.2%) | 4 (44.4%) |
| 18 | Enteropathy |
3 (33.3%) | 2 (22.2%) | 4 (44.4%) |
| 19 | Diarrhea |
3 (33.3%) | 2 (22.2%) | 4 (44.4%) |
| 20 | Lipodystrophy |
3 (33.3%) | 0 (0.0%) | 6 (66.7%) |
| 21 | Arthritis |
3 (33.3%) | 0 (0.0%) | 6 (66.7%) |
| 22 | Pneumonia |
3 (33.3%) | 2 (22.2%) | 4 (44.4%) |
| 23 | Erythema |
3 (33.3%) | 0 (0.0%) | 6 (66.7%) |
| 24 | Elevated serum GGT levels |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 25 | Elevated circulating ALT levels |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 26 | Cataract |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 27 | Hepatic steatosis |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 28 | Neonatal sepsis |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 29 | Lymphadenopathy |
2 (22.2%) | 1 (11.1%) | 6 (66.7%) |
| 30 | Pulmonary edema |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 31 | Increased serum complement C3 |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 32 | neutralising alpha-toxin antibodies |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 33 | Global developmental delay |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 34 | Joint swelling |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 35 | Hepatosplenomegaly |
2 (22.2%) | 2 (22.2%) | 5 (55.6%) |
| 36 | Myalgia |
2 (22.2%) | 1 (11.1%) | 6 (66.7%) |
| 37 | Elevated hepatic transaminases |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 38 | Vomiting |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 39 | Autoimmunity |
2 (22.2%) | 4 (44.4%) | 3 (33.3%) |
| 40 | Increased IgM levels |
2 (22.2%) | 1 (11.1%) | 6 (66.7%) |
| 41 | ASMA positivity |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 42 | Growth delay |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 43 | Premature birth |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 44 | Hyperferritinemia |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 45 | Increased IgG level |
2 (22.2%) | 2 (22.2%) | 5 (55.6%) |
| 46 | Autoimmune antibody positivity |
2 (22.2%) | 4 (44.4%) | 3 (33.3%) |
| 47 | Abdominal pain |
2 (22.2%) | 2 (22.2%) | 5 (55.6%) |
| 48 | Nasogastric tube feeding in infancy |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 49 | Skin infections |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 50 | Papulopustular Rash |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 51 | Grand mal seizures |
2 (22.2%) | 0 (0.0%) | 7 (77.8%) |
| 52 | Finger swelling |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 53 | Dependency on intravenous nutrition |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 54 | Increased circulating IL-6 |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 55 | Conjunctival hyperemia |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 56 | Hypertelorism |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 57 | Protruding ear |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 58 | Wide nasal bridge |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 59 | Prominent nose |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 60 | Elevated circulating AST levels |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 61 | Eosinophilic dermal infiltration |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 62 | Hematopoietic stem cell transplantation |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 63 | Thick eyebrow |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 64 | Persistent fever |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 65 | Carious teeth |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 66 | Localized osteoporosis |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 67 | Cortical cataract |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 68 | Cyanosis |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 69 | Atypical scarring of skin |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 70 | Hematuria |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 71 | Congenital hydrocele |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 72 | Septicaemia |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 73 | Parotitis |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 74 | Graft Versus Host Disease |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 75 | Antineutrophil antibodies |
1 (11.1%) | 1 (11.1%) | 7 (77.8%) |
| 76 | Elevated sIL-2R in serum |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 77 | Epidermal spongiosis |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 78 | Increased serum complement C1q |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 79 | Cutaneous lymphocytic infiltrates |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 80 | RSV pneumonia |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 81 | Gluteal abscess |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 82 | Vasculitis |
1 (11.1%) | 3 (33.3%) | 5 (55.6%) |
| 83 | Atrial septal defect |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 84 | Normocytic anemia |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 85 | Metabolic acidosis |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 86 | Pulmonary infiltrates |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 87 | Hyperkalemia |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 88 | Coarse hair |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 89 | Splenomegaly |
1 (11.1%) | 1 (11.1%) | 7 (77.8%) |
| 90 | Increased number of B cells |
1 (11.1%) | 1 (11.1%) | 7 (77.8%) |
| 91 | Duodenal ulcer |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 92 | Lymphadenitis |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 93 | Hyperphosphatemia |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 94 | Increased blood urea nitrogen |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 95 | Elevated circulating alkaline phosphatase concentration |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 96 | Elevated circulating creatinine concentration |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 97 | Acute kidney failure |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 98 | Anemia |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 99 | Predominantly lower limb lymphedema |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 100 | Obesity |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 101 | Hepatomegaly |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 102 | Sialadenitis |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 103 | Pneumothorax |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 104 | Hyperuricemia |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 105 | Cachexia |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 106 | erythema nodosum |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 107 | Respiratory failure |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 108 | Varicella zoster virus infection |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 109 | proteinuria |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 110 | Renal tubular epithelial necrosis |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 111 | (unusual) Viral infection |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 112 | Abnormal weight loss |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 113 | Monocytosis |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 114 | Ileus |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 115 | Lung abscess |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 116 | cirrhosis |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 117 | Cutaneous abscess |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 118 | Edema of the upper limbs |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 119 | sleep disturbance |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 120 | Epileptic spasm |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 121 | Eczema |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 122 | elevated ESR |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 123 | Mild global developmental delay |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 124 | Respiratory distress |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 125 | Splenic abscess |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 126 | Muscular hypotonia |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 127 | Broad chin |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 128 | Bloody diarrhea |
1 (11.1%) | 0 (0.0%) | 8 (88.9%) |
| 129 | Decreased IgA levels |
0 (0.0%) | 1 (11.1%) | 8 (88.9%) |
| 130 | Decreased IgG levels |
0 (0.0%) | 2 (22.2%) | 7 (77.8%) |
| 131 | Reduced NK cell number |
0 (0.0%) | 2 (22.2%) | 7 (77.8%) |
| 132 | Decreased IgM levels |
0 (0.0%) | 1 (11.1%) | 8 (88.9%) |
| 133 | Antinuclear antibodies |
0 (0.0%) | 1 (11.1%) | 8 (88.9%) |
| 134 | Reduced number of B cells |
0 (0.0%) | 2 (22.2%) | 7 (77.8%) |
| 135 | Reduced T cell count |
0 (0.0%) | 2 (22.2%) | 7 (77.8%) |
| 136 | Pancreatitis |
0 (0.0%) | 1 (11.1%) | 8 (88.9%) |
| 137 | Decreased serum complement C3 |
0 (0.0%) | 1 (11.1%) | 8 (88.9%) |
| 138 | Hypogammaglobulinemia |
0 (0.0%) | 2 (22.2%) | 7 (77.8%) |
| 139 | Unusual infection |
0 (0.0%) | 2 (22.2%) | 7 (77.8%) |
| 140 | Granulomatosis |
0 (0.0%) | 1 (11.1%) | 8 (88.9%) |
| 141 | Impaired oxidative burst |
0 (0.0%) | 2 (22.2%) | 7 (77.8%) |
Summary of treatment outcomes
[Considering only Definitive and Possible cases]
| Treatment ⓘ | Responses & clinical indications |
|---|---|
| Immunosuppressive agents | Absent (3) for unspecified. Moderate (3) for unspecified. Mild (1) for unspecified. Good (1) for Elevated C-reactive protein & Fever & Systemic autoinflammation; Systemic autoinflammation. Excelent/Remision (1) for Systemic autoinflammation. Unspecified (1) for unspecified |
| Infliximab | Good (1) for Elevated C-reactive protein & Fever & Leukocytosis & Neutrophilia & Skin rash & Systemic autoinflammation |
| Anti-TNF drug | Moderate (1) for unspecified. Good (1) for Systemic autoinflammation. Excelent/Remision (1) for Systemic autoinflammation |
| Adalimumab | Good (1) for Systemic autoinflammation |
| Corticosteroids | Moderate (3) for unspecified. Absent (2) for unspecified. Mild (1) for unspecified. Good (1) for Elevated C-reactive protein & Fever & Systemic autoinflammation. Unspecified (1) for unspecified |
| Azathioprine | Absent (2) for unspecified |
| Methotrexate | Absent (3) for unspecified |
| Prednisolone | Absent (2) for Diarrhea & Fever & Skin rash; unspecified. Mild (1) for Systemic autoinflammation. Good (1) for unspecified |
| Methylprednisolone | Moderate (1) for unspecified. Excelent/Remision (1) for Diarrhea & Fever & Skin rash. Unspecified (1) for unspecified |
| Anakinra | Absent (3) for Systemic autoinflammation; unspecified. Good (1) for unspecified |
| Interleukin Receptor Antagonist | Absent (3) for Systemic autoinflammation; unspecified. Good (1) for unspecified |
| Azithromycin | Unspecified (1) for unspecified |
| Acyclovir | Unspecified (1) for unspecified |
| Biological agents | Good (1) for Elevated C-reactive protein & Fever & Leukocytosis & Neutrophilia & Skin rash & Systemic autoinflammation |
| Monoclonal antibodies | Good (1) for Elevated C-reactive protein & Fever & Leukocytosis & Neutrophilia & Skin rash & Systemic autoinflammation |
| Antibiotics | Absent (2) for Systemic autoinflammation; unspecified. Unspecified (1) for unspecified |
| Colchicine | Negative/Bad (1) for unspecified. Mild (1) for Systemic autoinflammation |
| Anti-Inflammatory agents | Absent (1) for Diarrhea & Fever & Skin rash. Mild (1) for Systemic autoinflammation. Good (1) for unspecified. Excelent/Remision (1) for Diarrhea & Fever & Skin rash |
| Hematopoietic stem cell transplantation | Excelent/Remision (1) for Arthritis & Diarrhea & Fever & Panniculitis & Systemic autoinflammation. Unspecified (1) for unspecified |
| Etanercept | Moderate (1) for unspecified. Excelent/Remision (1) for Systemic autoinflammation |
| Antiviral agent | Unspecified (1) for unspecified |