Disease and Percentage of Cause Unknown

Disease and Percentage of Cause Unknown

Abdominal pain—25%-41% in the hospital setting1
41%
Achalasia—Almost all; only 1.4% to 5.4% have a known cause2
5.4%
Acoustic neuroma/Vestibular schwannoma—95%3,4
95%
Acquired generalized lipodystrophy—50%5
50%
Acquired hemophilia—50%6
50%
Acute gastroenteritis—25% to 49% or higher7,8,9
49%
Acute idiopathic blind spot enlargement—100% idiopathic, poorly understood10,11
100%
Acute liver failure—Almost half in children and 15% of adults12
15%
Acute transient synovitis—100% definitively unknown13
100%
Acute unilateral audiovestibulopathy—71%-90%14
90%
Acute unilateral uveitis—Up to 50%15
50%
Acute zonal occult outer retinopathy—100%16
100%
Addison’s disease—75%17
75%
Adenomyosis—100%18
100%
Adhesive capsulitis (primary)—100%19
100%
Adult idiopathic cholestasis—100%20
100%
Adult onset erythromelalgia (primary)—100%21
100%
Adult onset Still disease—100% cause undetermined definitively22
100%
Adult onset pulmonic stenosis—Rare but identified (adult onset is entirely idiopathic)23
100%
Adulthood ductopenia —Extremely rare but a few cases have been identified24
100%
Amyotrophic lateral sclerosis—90%-95%25
95%
Anal fissure (primary)—100%26
100%
Anal fistula—90%27,28
90%
Anaphylaxis—30%-60% in adults, 10% in children29
10%
Anetoderma (primary)—100%30
100%
Angioedema—Up to 40%31
40%
Ankylosing spondylitis—100% definitively unknown (gene identified)32
100%
Antiphospholipid syndrome (primary)—40%33,34
40%
Aortic dissection—Up to 80% (no family history or known genetic factors)35
80%
Aortitis—4.3% (large surgical cohort study)36
4.3%
Aplastic anemia—70%37
70%
Arteriovenous fistula—3%-5% of renal arteriovenous lesions38
5%
Ascites—Very rare but idiopathic is identified39,40
10%
Aseptic meningitis—35%-70%41,42
70%
Atrial fibrillation—3% (varies by study and definition)43
3%
Atrial myxoma—95%44
95%
Autoimmune hepatitis—100% cause definitively unknown45
100%
Avascular necrosis—40%46
40%
Axillary web syndrome—Idiopathic is identified but extremely rare47
100%
Barrett’s Esophagus—Unknown when not connected to GERD, no percentage, but idiopathic identified48
100%
Behcet disease—100%49
100%
Bell’s palsy—100%50
100%
Berger’s disease/IgA nephropathy—90%51,52
90%
Blood Clot—30% (US based)53
30%
Benign paroxysmal positional vertigo—50%-70%54
70%
Brachial neuritis—54%55
54%
Bronchiectasis—43% (English study)56
43%
Buerger’s disease—100%57
100%
Burning mouth syndrome—No percentage but idiopathic (primary) form proposed58
100%
Calcinosis cutis—Very rare but idiopathic is identified 59
Calcium oxolate urolithiasis—70%-80% of kidney stone patients have features, majority idiopathic60
80%
Cardiomyopathy—Up to 50%61
50%
Central retinal vein occlusion—25% in young people (under 40)62
25%
Central sleep apnea—4%-7%63,64,65
7%
Cerebellar ataxia—18.2% (Japanese study)66
18.2%
Cerebral venous thrombosis—15%-50%67,68,69
50%
Cerebrovascular fibromuscular dysplasia—100%70
100%
Cervical dysplasia—15% (HR-HPV negative)71
15%
Cervical polyps—100% definitive cause unknown72
100%
Cervicitis—61%73
61%
Chiari Type 1—70%74
70%
Cholecystitis—0.25%-6.4% (eosinophilic cholecystitis)75
6.4%
Chordae rupture—74.6%76,77
74.6%
Chorea—8%78
8%
Choroidal folds—10%-20%79
20%
Choroidal neovascularization—38.2% in pediatric population80
38.2%
Chronic carpal tunnel syndrome—50%81
50%
Chronic diarrhea—11% (one small study)82
11%
Chronic fatigue syndrome—100%83
100%
Chronic hiccups—Percentage unknown but idiopathic identified84
100%
Chronic idiopathic constipation—About 16% of the US population has this85
16%
Chronic intestinal pseudoobstruction—about 50% (Japanese study)86,87
50%
Chronic pelvic pain—33%-85%88,89
85%
Chronic recurrent multifocal osteomyelitis—100%90
100%
Chylothorax—Nearly 10%91
10%
Chylous pericardial effusion—56%92,93
56%
Cirrhosis—5% to 30%94
30%
Clinically isolated syndrome—Approximately 1/395
33%
Cluster headache (primary)—100%96
100%
CNS vasculitis (primary)—100%97
100%
Coat’s disease—100%98
100%
Colonic perforation—6.9% (Korean study)99
6.9%
Constrictive pericarditis—46%-55% in developed countries100,101
55%
Coronary artery spasm—20%-30%102
30%
Costochondritis—100% definitive cause unknown103,104
100%
Creutzfeldt-Jakob disease—80%-90%105
90%
Crohn’s disease—100%106
100%
Cryoglobulinemia—10%-30%107,108
30%
Cryptogenic organizing pneumonia—100%109
100%
Cutaneous vasculitis—40%-55%110
55%
Cyclical nausea and vomiting—100% unknown definitive etiology, autonomic neuropathy proposed111
100%
Dent disease—25%-35%112
35%
Dermatomyocytis—100%113
100%
Diffuse esophageal spasm—100%114
100%
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia syndrome—100%115
100%
Diffuse idiopathic skeletal hyperostosis (DISH)—100% unknown etiology, some risk factors identified116
100%
Dilated cardiomyopathy—50%117
50%
Discoid lupus erythematosus—100% (autoimmune)118
100%
Diverticulitis—50%-60% not identifiable through genetic risk factors119
60%
Diverticulosis—100% definitive cause unknown120
100%
Drop attacks—65%121
65%
Dumping syndrome—54% (one review)122
54%
Dysarthria—Percentage not established, idiopathic identified123
100%
Dysgeusia—34%124
34%
Dyspepsia—Up to 60%125
60%
Dyssynergia—40%126,127
40%
Dystonia—45.3% (Saudi Arabia study)128
45.3%
Ectopic pregnancy—50%129
50%
Edema 9%-25% in some populations130,131
25%
Electrical alternans—20%132
20%
Embolic limb ischemia—15%-20%133,134
20%
Emphysema—10%135
10%
Encephalitis—20%-60%136,137
60%
Endometrial polyps—100% definitive cause unknown138
100%
Endometriosis—100% (definitive cause unknown)139
100%
Endomyocardial fibrosis—87%140
87%
Enterocolic lymphocytic phlebitis—Entirely unknown etiology, 68% in review found to have associated disease141
68%
Eosinophilic pleural effusion—14%-25%142
25%
Epilepsy—15%-20%143
20%
Epiretinal membrane (primary)—100%144
100%
Episcleritis—64%-74%145
74%
Epistaxis—38.09%-70%,-80%-90%146,147,148,149
90%
Erythema multiforme—58% (small Mayo Clinic study)150
58%
Erythema nodosum—30%-50%151
50%
Erythrocytosis—Up to 70%152
70%
Essential Tremor—100% (50% hypothesized as familial)153
50%
Extramedullary hematopoiesis—4% (Mayo Clinic study)154
4%
Fahr’s disease—Percentage unknown but idiopathic is identified155
100%
Fever of unknown origin (adult)—25%-50%156
50%
Fibromyalgia—100%157
100%
First bite syndrome—12.5% (single small study)158
12.5%
Focal segmental glomerulosclerosis (primary)—100%159
100%
Foveal atrophy—Percentage unknown but idiopathic is identified160
100%
Gallstone disease—45.7% (single pediatric study)161
45.7%
Gastric volvulus—1/3rd162
33%
Gastrinomas—75%-80%163
80%
Gastroparesis—At least 11%164
11%
GI bleed—5%165,166
5%
Giant cell arteritis—100%167
100%
Glaucoma—90% of US presentations (primary open-angle has unknown cause)168
90%
Goodpasture syndrome—Autoimmune169
100%
Graft vs host—40%170
40%
Granulomatosis with polyangiitis—100% (autoimmune)171
100%
Granulomatous gastritis—About 25%172,173
25%
Granulomatous hepatitis—10%-36%174,175
36%
Gynecomastia—25%176
25%
Hashimoto’s disease—About 5%-10% are seronegative177,178
10%
Heart failure with preserved ejection fraction—55%179
55%
Heart palpitations—16% (single study)180
16%
Hemarthrosis—Rare but idiopathic is identified181,182
100%
Hemifacial spasm—62%183
62%
Hemochromatosis—3.43% (Italian study)184
3.43%
Hemolytic anemia—50%185
50%
Hemoperitoneum—30%-38%186
38%
Hemophagocytic lymphohistiocytosis—10%-17.8%-35.8%187,188,189
35.8%
Hemoptysis—7%-34%190,191
34%
Hemorrhagic stroke—19% in pediatric192
19%
Hemorrhoids—100% definitively unknown193
100%
Henoch Schonlein purpura—100%194
100%
Hepatic hemangioma—100%195
100%
Hiatal hernia—15–20% 495
15–20%
Hirschsprung's disease—80% have no known familial genetic link196
80%
Hirsutism—10% (50% in mild cases)197
50%
Horner syndrome—36.4% (small pediatric study), 25.6%(small adult study)198,199
25.6%
Hydronephrosis—42% in neonates (single study)200
42%
Hyperacusis—No specific percentage but poorly understood etiology overall201,202
100%
Hypercalcemia—Less than 5% but idiopathic is identified203
5%
Hyperemesis gravidarum—100% definitive cause unknown204
100%
Hypereosinophilic syndrome—55% (European study)205
55%
Hyperhidrosis (primary)—100%206
100%
Hyperprolactinemia—5.2%-47.3%207,208
47.3%
Hypersomnia—0.002%-0.010% incidence in the general population209
0.01%
Hypertrophic cardiomyopathy—40%210
40%
Hypertrophic cranial pachymeningitis—57%-67%211,212
67%
Hypertrophic pyloric stenosis—100% unknown etiology in pediatric and adult213
100%
Hyperventilation syndrome (primary)—100%214
100%
Hypocalcemia/Hypoparathyroidism—16%215
16%
Hypogonadism—About 50%216
50%
Hyponatremia/syndrome of inappropriate antidiuretic hormone secretion —15.9%-39.2%, 60% in the elderly217
60%
Hypopituitarism—10.6% (Turkish study)218,219
10.6%
Hypothyroidism—15% (Japanese study)220
15%
Hypotonia—50%221
50%
Idiopathic atrophy of the nails—100% Very rare but identified222
100%
Idiopathic calcified myocardial mass—100%223
100%
Idiopathic central serous chorioretinopathy—100%224
100%
Idiopathic condylar resorption—100%225
100%
Idiopathic dendriform pulmonary ossification—100%226
100%
Idiopathic enlargement of the right atrium—100% idiopathic227
100%
Idiopathic granulomatous mastitis—100%228
100%
Idiopathic granulomatous orchitis—100%229
100%
Idiopathic hyperventilation—100%230
100%
Idiopathic hypovolemia syndrome—100%231
100%
Idiopathic intracranial hypertension—100%232
100%
Idiopathic labyrinthitis—Percentage unknown but idiopathic is identified271
100%
Idiopathic multifocal choroiditis—100%238
100%
Idiopathic pulmonary hemosiderosis—100%242
100%
Idiopathic systemic capillary leak syndrome—100%249
100%
Inclusion body myositis—100%251
100%
Incompetent cervix (primary)—100%252
100%
Infantile spasms—35.7% (small Pakistani study)253
35.7%
Inflammatory amyloidosis—Almost 25%254
25%
Inflammatory bowel disease—100%255
100%
Interstitial nephritis—10%-28%233,234
28%
Intestinal pneumatosis—15%258
15%
Intracranial aneurysm—72.7% in infants259
72.7%
Intrahepatic cholestasis of pregnancy—100%260
100%
Intussusception—75% children, 10% adults261,262
10%
Irritable bowel syndrome—100%263
100%
Ischemic stroke—30%-40%264
40%
Isolated hypoglossal nerve palsy—50%265
50%
Isolated idiopathic teres minor atrophy—100%266
100%
Juvenile myoclonic epilepsy—100% definitively unknown (hereditary genetics possible in 50%)267
50%
Kawasaki disease—100%268
100%
Keratoacanthoma—100%269
100%
Keratosis pilaris—100%270
100%
Kidney allograft failure—5.8%271
5.8%
Kidney stones—44% of pediatric (long-term single-center study), 40%-50% of chronic patients have idiopathic hypercalciuria235,236
50%
Laryngeal dystonia—100%273
100%
Legg-Calve-Perthes disease—100%274
100%
Leukocytosis—12.5% (single study)275
12.5%
Lewy body dementia—100%276
100%
Lichen planus—Majority277
100%
Lichen sclerosus—100% definitively unknown (suspected autoimmune)278
100%
Light chain deposition disease—Less than 50%279
50%
Lipoma—100% definitively unknown (2/3rds have genetic abnormality)280
100%
Long QT syndrome—20% no known genetic cause281,282
20%
Low systemic vascular resistance—7% (single study)283
7%
Lymphocytic gastritis—Up to 20%284
20%
Macular degeneration—100% definitively unknown (risk factors identified)285
100%
Macular hole—80%-83%286,287
83%
Macular neuroretinitis—50%288,289
50%
Macular telangiectasia type 2—100%290
100%
Male infertility—30%291
30%
Mallory-Weiss tear—25%292
25%
Mast cell activation—4.4%293
4.4%
Mediastinal fibrosis—Up to 58% in locations without endemic histplasmosis294
58%
Megacolon—66.7% in adults (one review, may lack clear definitions)295
66.7%
Membranous nephropathy—75%296
75%
Menetrier disease—100% definitive cause unknown297
100%
Meniere’s (primary)—100%298
100%
Mesenteric panniculitis—2/3rds (single study)299
100%
Mesenteric phlebosclerosis—100% unknown etiology but may be associated with use of herbal medicine300,301
100%
Microcytic anemia—18% (Dutch study)302
18%
Mid-aortic syndrome—64%303,304
64%
Middle ear myoclonus—100% definitive cause unknown305
100%
Mild idiopathic oxaluria—100% of this type306
100%
Minimal change disease—70%-90% of children with nephrotic syndrome, 10%-15% of adults with idiopathic nephrotic syndrome307,308
15%
Mitral valve prolapse—50%-65% (no familial genetic component, other risk factors identified)309
65%
Myelin oligodendrocyte glycoprotein antibody-associated disease—100%310
100%
Mononeuritis multiplex—33%311,312
33%
Mooren’s ulcer—100%313
100%
Multicentric Castleman disease—33%-50%314
50%
Multiple sclerosis—100%315
100%
Multisystem atrophy/Shy-Drager syndrome—100%316
100%
Myasthenia gravis—Mostly idiopathic (autoimmune)317
100%
Myelofibrosis—10% do not have a known causal mutation318
10%
Myelopathy—18.1%319
18.1%
Myocarditis—50%320
50%
Myoclonus—4.66%321
4.66%
Nasal polyps—100%322
100%
Nephrotic syndrome—90% in children, 80%-90% in adults323,324
90%
Neuralgic amyotrophy—Idiopathic is 10x more likely than hereditary325
40%
Non-puerperal uterine inversion—9.2%327
9.2%
Normal pressure hydrocephalus—Could be up to 14% in some populations, varies widely by study327
14%
Obliterative bronchiolitis—5%-42%328,329
42%
Olfactory loss—6%-30%330
30%
Oligohydramnios—50% (single study)331
50%
Ophthalmoplegia—36% (small Indian study)332
36%
Optic neuritis—46%-Approximately 50%333,334
50%
Orbital inflammation—8%-10% of orbital mass lesions340
10%
Orthostatic hypertension—29%-1/3rd335,336
40%
Ovarian granulomas—16% (single small study)338
16%
Paget’s disease—100%339,340
100%
Pancreatitis—15%-25% of acute and up to 9% of chronic (European study)343,344
9%
Pancytopenia—50%345
50%
Paraproteinemia/Monoclonal gammopathy of undetermined significance—2/3rds of plasma cell dyscrasias346
100%
Parkinson’s—85%347
85%
Paroxysmal tonic upward gaze—Percentage unknown but idiopathic is identified348
100%
Patulous eustachian tube dysfunction—1/3rd349
33%
Peliosis hepatis—20%-50%350
50%
Pelvic inflammatory disease—15%-55%351,352,353
55%
Pemphigus—100%354
100%
Peptic ulcers—11%-44%355
44%
Pericarditis—80%-90% in developed countries356
90%
Periorbital myokymia—100% not definitively understood357
100%
Peripheral neuropathy—30%-40%358,359
40%
Peritonsillar abscess—37.27% (no pathogen found)360
37.27%
Pharyngitis—30%361
30%
Pheochromocytoma—70%362
70%
Physiologic jaundice of the newborn—32% (single Indian study)363
32%
Pituitary adenoma—95%364
95%
Pityriasis alba—100%365
100%
Placental abruption—100% (some risk factors identified)366
100%
Placental insufficiency—60%367,368
60%
Pleurisy—30%-40%369
40%
Plummer-Vinson syndrome—100%370
100%
Pneumacystoides intestinalis—15%371
15%
Polyarteritis nodosa—80%372,373
80%
Polycystic kidney disease—15% (no familial link)374
15%
Polyhydramnios—50%-60%375,376
60%
Polymyalgia rheumatica—100%377,378
100%
Polymyositis—100%379
100%
Polyneuropathy—20%-30%380
30%
Porphyria cutanea tarda—75%-80%381
80%
Portal vein thrombosis—8%-15%,25%382,383
30%
Postpartum hemorrhage—20%384
20%
Preeclampsia—100% definitively unknown385
100%
Postural orthostatic tachycardia syndrome—Up to 50% attributed to post-viral illness; the rest is debated284
50%
100%
Premature labor—45%-50%386
50%
Premature ovarian insufficiency—39%-67%387,388
67%
Priapism—50%389
50%
Primary aldosteronism—60%-70%390
70%
Primary lateral sclerosis—100%391
100%
Primary osteoarthritis—100% cause not definitive392
100%
Primary sclerosing cholangitis—100%393
100%
Prinzmetal angina—100% definitively unknown394
100%
Progressive supranuclear palsy—100%395
100%
Prolonged prothrombin time—9% (single study)396
9%
Proptosis—18%-19.6%397,398
19.6%
Pruritis—8%-15%399
15%
Pseudo gout—Majority400,401
100%
Psoriasis—100% definitively unknown402
100%
Pulmonary arterial hypertension—39%-61%403
61%
Pulmonary embolism—16.5%-69%404,405
69%
Pulmonary fibrosis—Approximately 19% to 39%406
39%
Pulmonic regurgitation—10% in moderate/severe407
10%
Pyoderma gangrenosum—20%-30%408
30%
Pyometra—74.1% (single study)409
74.1%
Rapid gastric emptying—22.6% (one study)447
22.6%
Recurrent aphthous ulcer—100%244
100%
Recurrent pregnancy loss—50%411
50%
Refractory Sideroblastic Anemia—100%245
100%
REM sleep behavior disorder—60%412
60%
Renal arteriovenous fistula—3%-5%413
5%
Renal arteriovenous malformation—Up to 5%414
5%
Renal infarction—Up to 59% (varies by study)415
59%
Renal tubular acidosis (type 1)—55% (single study)416
55%
Restless leg—100% (Primary type, may be familial in up to 75%)417
75%
Retinal detachment—50%418
50%
Retroperitoneal fibrosis—Over 70% but of that, 35% to 60% IgG4-related419
60%
Reversible cerebral vasoconstriction syndrome—20%-50%420
50%
Reynaud’s phenomenon—80%-90%410
90%
Rhabdomiolysis—7%,12% in the elderly421,422
12%
Rhinitis—about 50%423
50%
Right ventricle hypertrophy—Rare but idiopathic is identified424
100%
Sarcoidosis—100%425,426
100%
Scheuermann's disease/Idiopathic kyphosis—100%427
100%
Scleroderma—100% (autoimmune)428
100%
Sclerosing encapsulating peritonitis—Very rare but happens429
100%
Scoliosis—80%-90%430
90%
Seborrheic dermatitis—100%431
100%
Seborrheic keratosis—100% definitively unknown (risk factors identified)432
100%
Semicircular canal dehiscence—100%433,434
100%
Sjogren’s—40% (autoimmune)435
40%
Spasmodic dysphonia—100%436
100%
Sphincter of Oddi dysfunction—30%-65% of patients with idiopathic acute recurrent pancreatitis437
65%
Spinal cord infarct—20%-47.3%438,439
47.3%
Spontaneous hemopneumothorax—Rare but idiopathic identified440
50%
Spontaneous spinal epidural hematoma—40%-50%441
50%
ST-elevation myocardial infarction—19%442
19%
Stable angina—Over 50%443
50%
Stiff person syndrome—20% (seronegative)444
20%
Subarachnoid hemorrhage—19%445
19%
Subdural hematoma—Percentage is unknown but idiopathic is identified446
100%
Subglottic stenosis—19%447
19%
Sudden sensorineural hearing loss—90%448
90%
Syncope—14%-39%449
39%
Tarsal tunnel syndrome—20%450
20%
Telogen effluvium—33%451,452
33%
Thrombocytosis—10%-20%453
20%
Tinnitus—65%-98%454
98%
Tolosa-Hunt syndrome—100%455
100%
Tonic-clonic seizures—15 to 34 years: 85% idiopathic, 35 to 64 years: 60% idiopathic, 5 years and older: 50% idiopathic456,457
50%
Torticollis—80%-90%458
90%
Transverse Myelitis—15%-30% up to 64%459
64%
Tricuspid aortic regurgitation—21.8%-34.1%461,462
34.1%
Trigeminal neuralgia—10%463
10%
Troponin elevation—35%464
35%
Tumor lysis syndrome—24%465
24%
Type 1B diabetes—100%466
100%
Ulcerative colitis—100%467
100%
Uncal herniation—Extremely rare but idiopathic is identified468
100%
Unilateral vocal fold paralysis—29%-67%469,470
67%
Upper extremity digital ischemia—11.7%471
11.7%
Urethritis—50% (non-gonococcal)472
50%
Urticaria—80%-90%473
90%
Uterine leiomyomata—100% exact cause unknown 474,475
100%
Uveal effusion syndrome type 3—100%474,475
100%
Vaginitis—up to 30%476
30%
Venous thromboembolism—25%-50%477,478
50%
Ventricular fibrillation—5%-10% of survivors of cardiac arrest out of the hospital481
10%
Ventricular tachycardia—10%482,483
10%
Villous atrophy—Up to 14% of adult patients (variable by study, poor definitions)484
14%
Vogt–Koyanagi–Harada syndrome—100% (autoimmune)485
100%
Vulvodynia—100%486
100%
West syndrome—5%–30%250
30%
Wunderlich syndrome—6.7%489,490
6.7%
Xanthelasma palpebrarum—50%491
50%
Zenker’s diverticulum—100%492, 493
100%
Zollinger–Ellison syndrome—100%494
100%

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