Lysozyme amyloid related amyloidosis: Difference between revisions

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==Differentiating lysozyme amyloid related amyloidosis from Other Diseases==
==Differentiating lysozyme amyloid related amyloidosis from Other Diseases==
Lysozyme amyloid related amyloidosis must be differentiated from other types of familial amyloidosis and other diseases that mimic amyloidosis and may present as organ dysfunction, specifically, [[nephrotic syndrome]] leading to [[renal failure]], [[cardiac failure]] and [[polyneuropathy]].
Lysozyme amyloid related amyloidosis must be differentiated from other types of familial amyloidosis and other diseases that mimic amyloidosis and may present as organ dysfunction, specifically, [[nephrotic syndrome]] leading to [[renal failure]], [[cardiac failure]] and [[polyneuropathy]].
 
For more information on the differential diagnosis of lysozyme amyloid related amyloidosis [[Familial amyloidosis differential diagnosis|click here]]
{|
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Organ System Involvement}}
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Differential Diagnosis}}
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Causes}}
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Clinical Features}}
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Laboratory Findings}}
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Gold Standard Test}}
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Therapy}}
|-
! rowspan="9" style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Nephrotic Syndrome and Real Failure
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Familial Amyloidosis
| style="padding: 5px 5px; background: #F5F5F5;" |
* Genetic mutation
| style="padding: 5px 5px; background: #F5F5F5;" |
* Parasthesia
* Muscle weakness
* Sexual problems
* Constipation/ diarrhea
* Urination problems
* Weakness
* Fatigue
* Edema
* Palpitation
* Dizziness
| style="padding: 5px 5px; background: #F5F5F5;" |
* ncreased:I
 
:* [[Troponin I]] or [[Troponin T|TroponinT]]
:* [[BNP]] and [[NT-proBNP]]
:* [[AST]]
:* [[ALT]]
:* Total [[bilirubin]]
:* [[Alkaline phosphatase]]
:* [[Creatinine|Serum creatinine]]
:* [[Urinary]] [[protein]]
:*
| style="padding: 5px 5px; background: #F5F5F5;" |
* Biopsy:
** Apple green birefringence of the tissue sample under polarized light with Congo red stain.
| style="padding: 5px 5px; background: #F5F5F5;" |
* Liver transplant for TTR amyloidosis
* Organ specific transplant
* Tafamidis
* Patisiran and Inoteresen
* Diflunisal
* Epigallocathechin-3-gallate <br />
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Primary (AL) Amyloidosis
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Monoclonal]] [[plasma cell]] proliferation
* Extracellular [[amyloid]] fibril deposition
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Anasarca]]
*[[Bleeding tendency]]
* Swelling of [[lower limbs]]
* Frothy [[urine]]
*[[Chest pain]]
*[[Numbness]] or [[tingling]]
*[[Early satiety]]
*[[Joint pains]]
*[[Macroglossia|Enlarged tongue]]
*[[Taste loss]]
*[[Hoarseness|Hoarseness of voice]]
*[[Alopecia|Hair loss <br />]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Increased [[erythrocyte sedimentation rate]] ([[ESR]])
* Increased [[Alanine aminotransferase|alanine aminotrasnferase]] ([[Alanine transaminase|ALT]]) and [[Aspartate aminotransferase|aspartate aminotrasnferase]] ([[Aspartate transaminase|AST]])
* Increased [[Cardiac troponin I (cTnI) and T (cTnT)|cardiac troponins]]
* Increased [[brain natriuretic peptide]] ([[BNP]])
* Increased [[blood urea nitrogen]] ([[BUN]]) and [[creatinine]]
*[[Proteinuria]]
* Urinary [[Hyaline cast|hyaline]] and fatty casts
*[[Hypercholesterolemia]]
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
* Biopsy:
** Diffuse glomerular deposition of amorphous [[hyaline]] material (nodular pattern - 8 to15 nm in diameter), in [[mesangium]] (weakly staining with [[Periodic acid-Schiff stain|periodic acid-Schiff]] ([[Periodic acid-Schiff stain|PAS]])
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Melphalan]]-[[prednisone]]/[[dexamethasone]]
*[[Dexamethasone]] plus [[Cyclophosphamide]]-[[thalidomide]]
*[[Stem cell transplantation]]
*[[Kidney transplantation]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Diabetic nephropathy|Diabetic Nephropathy]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Hyperfiltration
* Constriction of [[efferent arteriole]]
*[[Microalbuminuria]]
*[[Mesangial cell|Mesangial]] proliferation
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Nocturia]]
*[[Fatigue]]
*[[Pruritis]]
*[[Peripheral edema]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Hyperglycemia]] (random plasma glucose ≥200 mg/dL)
*[[Proteinuria]]
*[[Glucosuria]]
*[[Glycosylated hemoglobin|HbA1C]] ≥6.5% (48 mmol/mol). <br />
| style="padding: 5px 5px; background: #F5F5F5;" |
* Biopsy:
**[[Periodic acid-Schiff stain|PAS]] positive [[Kimmelstiel-Wilson syndrome|Kimmelstiel-Wilson nodules]]
**[[Glomerulosclerosis]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[ACE inhibitor|ACE inhibitors]]
*[[Angiotensin receptor blockers]]
*[[Glycemic]] control
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Minimal change disease|Minimal Change Disease]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Upper respiratory tract infection]]
*[[Allergy]] to bee sting
*[[Non-steroidal anti-inflammatory drug|NSAID]]
*[[Gold]]
*[[Penicillamine]]
*[[Ampicillin]]
*[[Mercury (element)|Mercury]]
*[[Hodgkin's lymphoma|Hodgkin's]] and [[Non-Hodgkin lymphoma|non-Hodgkin's lymphoma]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Peripheral edema]]
*[[Hypertension]]
*[[Peripheral edema]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Proteinuria]]
*[[Hypertension]]
*[[Hyperlipidemia]]
*[[Hypoalbuminemia]]
*[[Microscopic hematuria]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Biopsy:
** Fused [[podocytes]]/effacement
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Prednisone]] with taper
*[[ACE inhibitor|ACE inhibitors]]
*[[Angiotensin receptor blockers]]
* Salt restriction
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Focal segmental glomerulosclerosis|Focal Segmental Glomerulosclerosis]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[HIV]]
*[[Parvovirus B19]]
*[[Cytomegalovirus]]
*[[Heroin]]
*[[Interferon alpha]]
*[[Lithium]]
*[[Pamidronate]]/aledronate
*[[Anabolic steroids]]
*[[Diabetes mellitus]]
*[[Hypertension]]
*[[Obesity]]
*[[Congenital heart disease cyanotic|Cyanotic congenital heart disease]]
*[[Sickle cell anemia]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Peripheral edema]]
*[[Hypertension]]
*[[Peripheral edema]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Proteinuria]]
*[[Hypertension]]
*[[Hyperlipidemia]]
*[[Hypoalbuminemia]]
*[[Microscopic hematuria]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Biopsy:
**[[Podocytes|Podocyte]] foot process effacement
**[[Capillary]] lumen abolished by the segmental increase in matrix <br />
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Prednisone]]
*[[Calcineurin inhibitor|Calcineurin inhibitors]] ([[Cyclosporine|Cyclosporin]], [[tacrolimus]])
*[[Rituximab]]
*[[Cyclophosphamide]]/[[chlorambucil]]
*[[Mycophenolate|Mycophenolate motefil]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Fabry's disease|Fabry's Disease]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Deficient alpha galactosidase A
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Abdominal pain]]
*[[Arthralgia]]
*[[Febrile]] episodes
*[[Angiokeratomas]]
* Burning pain and tingling ([[Peripheral neuropathy|peripheral neuropathy)]]
*[[Hypohidrosis]]
*[[X-linked recessive]] inheritance
| style="padding: 5px 5px; background: #F5F5F5;" |
* Deficient alpha galactosidase A
* Increased ceramide trihexoside ([[Globotriaosylceramide 3-beta-N-acetylgalactosaminyltransferase|globotriaosylceramide]])
| style="padding: 5px 5px; background: #F5F5F5;" |
* Alpha-galactosidase A activity
*[[GLA|GLA gene]] analysis for [[Heterozygote|heterozygotes]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Enzyme replacement therapy
*[[ACE inhibitor|ACE inhibitors]]
*[[Gabapentin]], [[carbamazepine]]
*[[Migalastat]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Light Chain Deposition Disease
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Multiple myeloma]]
*[[Waldenström's macroglobulinemia]]
*[[Monoclonal gammopathy of undetermined significance]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Asymptomatic]]
*[[Fatigue]]
*[[Weight loss]]
*[[Dyspnea]]
*[[Peripheral edema]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Proteinuria]]
*[[Portal hypertension]]
* Increased [[Alanine transaminase|ALT]], [[Aspartate transaminase|AST]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Biopsy:
** Non-amyloid granules
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Bortezomib]]
* Autologous [[stem cell transplantation]]
* Immunomodulatory drugs
*[[Kidney transplantation|Kidney transplant]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Membranous glomerulonephritis|Membranous Glomerulonephritis]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Hepatitis B]] and [[Hepatitis C|C]]
*[[HIV]]
*[[Non-Hodgkin lymphoma|Non-Hodgkin`s lymphoma]]
*[[Chronic lymphocytic leukemia]]
*[[Hodgkin lymphoma|Hodgkin`s lymphoma]]
* Solid tissue tumors
*[[Schistosomiasis]]
*[[Leprosy]]
*[[Hydatid disease]]
*[[Loaiasis]] (filaria)
*[[Malaria|Quartan malaria]]
*[[Systemic lupus erythematosis]] ([[SLE]]) <br />
| style="padding: 5px 5px; background: #F5F5F5;" |<br />
 
*[[Headache]]
*[[Edema]] affecting any area of the body
* Foamy appearance of urine
*[[Weight gain]]
*[[Poor appetite]]
*[[Nocturia]]
*[[Fatigue]]
*[[Hematuria]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Proteinuria]]
*[[Hypertension]]
*[[Hyperlipidemia]]
*[[Hypoalbuminemia]]
* Microscopic or gross hematuria
*[[Hypoalbuminemia]]
*[[Antinuclear antibodies|ANA]] and [[Anti-dsDNA antibody|anti-dsDNA]] positivity
| style="padding: 5px 5px; background: #F5F5F5;" |
* Biopsy:
**[[Immunoglobulin G|IgG]] and [[C3 (complement)|C3]] deposits with thickened [[basement membrane]] with spikes and vacuolization
**[[Glomerulosclerosis]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Prednisone]]
*[[Methylprednisolone]] with [[cyclophosphamide]]
*[[Tacrolimus]] with a six-month taper
*[[Rituximab]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Fibrillary-Immunotactoid Glomerulopathy
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Idiopathic]]
*[[Hepatitis C]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Microscopic or [[Hematuria|gross hematuria]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Proteinuria]]
*[[Hypertension]]
*Increased [[blood urea nitrogen]] ([[Blood urea nitrogen|BUN]]) and [[creatinine]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Biopsy:
** Polycloncal [[Immunoglobulin G|IgG]] deposits
** Infiltration of glomerular structures by amorphous acellular material (nonbranching fibrils 12-24nm in diameter)
** Ig heavy-chain and one light-chain subclass
| style="padding: 5px 5px; background: #F5F5F5;" |
|-
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Organ System Involvement}}
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Differential Diagnosis}}
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Causes}}
! style="background: #4479BA; width: 300px;" |{{fontcolor|#FFF| Clinical Features}}
! style="background: #4479BA; width: 300px;" |{{fontcolor|#FFF|Laboratory Findings}}
! style="background: #4479BA; width: 300px;" |{{fontcolor|#FFF|Gold Standard Test}}
! style="background: #4479BA; width: 300px;" |{{fontcolor|#FFF|Therapy}}
|-
| rowspan="6" style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''''Polyneuropathy'''''
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[POEMS syndrome]] (Demyelinating)'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Monoclonal]] [[plasma cell]] proliferation
*[[Cytokine]] storm ([[IL-1]], [[Interleukin 6|IL-6]], [[Interleukin 12|IL-12]], [[TNF alpha]], [[VEGF]])
| style="padding: 5px 5px; background: #F5F5F5;" |
* Symmetrical, ascending chronic progressive [[polyneuropathy]] with both [[Sensory system|sensory]] (pin-prick and vibration) and [[Motor skill|motor]] disability ([[Motor skill|motor]] > [[sensory]])
* Generalized/extermity [[pain]]
*[[Areflexia]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*Increased number of [[Platelet|thrombocytes]]
*Increased number of [[Red blood cell|erythrocytes]]
*Elevated [[Cerebrospinal fluid|cerebrospinal fluid (CSF)]] [[protein]] content
*Increased number of [[White blood cells|leukocytes]]
*High levels of [[Immunoglobulin G|IgG]] lambda or [[Immunoglobulin A|IgA]] lambda [[M protein|M-protein]] in the [[serum]]
*Increased number of [[Plasma cell|plasma cells]] in the [[bone marrow]]
*Increased serum [[Vascular endothelial growth factor|VEGF]] level
*Elevated levels of antitiroglobulin [[antibody]] and antithyroid peroxydase [[antibody]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[POEMS syndrome diagnostic criteria|International Myeloma Working Group (IMWG) clinical and laboratory diagnostic criteria]]
| style="padding: 5px 5px; background: #F5F5F5;" |
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Metabolic syndrome|Metabolic Syndrome]] (Axonal pathology)'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Diabetes mellitus]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Symmetric sensorimotor distal polyneuropathy
* Asymmetric proximal neuropathy
*[[Oculomotor nerve palsy|3rd nerve palsy]]
*[[Carpal tunnel syndrome|Carpel tunnel syndrome]]
*[[Autonomic neuropathy]]
* "Glove and stocking" type pain
*[[Muscle wasting]]
*[[Hammer toe|Hammer toes]]
*[[Polyuria]]
*[[Polydipsia]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Uncontrolled [[hyperglycemia]]
* Slowed [[Nerve conduction study|nerve conduction]]
*[[Small fiber peripheral neuropathy|Small fiber dysfunction]]
*[[Monofilament|Monofilament testing]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Fasting blood sugar|Fasting blood sugar level]] greater than equal to 126 mg/dl on 2 separate occasions
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Diabetes mellitus medical therapy|Anti-diabetic therapy]]
*[[Gabapentin]]
*[[Carbamazepine]]
*[[Foot care]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Vitamin deficiencies|Vitamin Deficiencies]] (Axonal Pathology)'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Vitamin B12 deficiency]] (Decreased [[S-Adenosyl methionine|S-adenosyl methionine]])
*[[Thiamine deficiency|Vitamin B1 deficiency]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Primarily [[sensory]] deficits
* Vibration and [[proprioception]] affected
*[[Gait abnormality|Gait abnormalities]]
*[[Cognitive impairment]]
*[[Irritability]]
*[[Glossitis]]
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Anemia]] ([[Megaloblastic Anemias|megaloblastic]] in case of [[Vitamin B12 deficiency|B12 deficiency]])
* Decreased [[serum]] [[Vitamin B12]] levels (< 200 pg/ml)
*[[Methylmalonic acidemia|Elevated methylmalonic acid]]
*
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Serum]] [[Vitamin B12]] levels
*[[Methylmalonic acid|Methylmalonic acid levels]]
*[[Intrinsic factor|Intrinsic factor antibodies]]
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Vitamin B12]] supplement ([[parenteral]])
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Guillain-Barré syndrome|Guillain-Barre Syndrome]] (Demyelinating)'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Anti-ganglioside antibodies|Anti-ganglioside]] and anti-[[myelin]] antibodies
*[[Viral]] infections:
**[[Epstein Barr virus]]
**[[Human Immunodeficiency Virus (HIV)|HIV]]
**[[Cytomegalovirus]]
**[[Varicella Zoster Virus|Varicella Zoster virus]]
*[[Bacterial]] infections:
**[[Campylobacter]] infection
**[[Mycoplasma pneumoniae]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Rapid onset and quick progression
* Progression stops after 2-3 weeks
* Bilateral ascending [[Paraesthesia|paraesthesias]] and [[paralysis]] (generalized)
*[[Muscle weakness|Weakness]]
*[[Ataxia]]
*[[Areflexia]]
* No fever
* 4 sub-types:
**[[Acute inflammatory demyelinating polyneuropathy]]
**[[Acute motor axonal neuropathy]]
**Acute motor and sensory axonal neuropathy
**[[Miller Fisher syndrome]]
 
| style="padding: 5px 5px; background: #F5F5F5;" |
* Delayed F waves
| style="padding: 5px 5px; background: #F5F5F5;" |
* Clinical diagnostic criteria (progressive weakness of more than two [[limbs]], [[areflexia]], and progression for no more than four weeks)
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Intravenous]] [[immunoglobulins]]
*[[Plasma]] exchange
*[[Mechanical ventilation|Respiratory support]]
*[[DVT]]/[[PE]] [[prevention]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Chronic inflammatory demyelinating polyneuropathy|Chronic Inflammatory Demyelinating Polyneuropathy]] (CIDP) (Mixed axonal and demyelinatiing)'''
| style="padding: 5px 5px; background: #F5F5F5;" |
* Abnormal [[immune response]] (both [[Immunoglobulin G|IgG]] based [[Humoral immunity|humoral]] and [[Cell mediated immunity|T-Cell mediated]]) response to unknown [[antigen]] (possible culprits include [[myelin]] [[proteins]] P0, P2 and PMP22)
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
* Slow onset and gradual progression
*[[Relapse|Relapsing]] and remitting course
* Symmetrical [[Proximal muscle weakness|proximal]] and [[Distal muscle weakness|distal motor]] and [[Sensory system|sensory weakness]] (legs>arms)
*[[Foot drop]]
*[[Numbness]], [[tingling]] and [[pain]]
*[[Areflexia]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Elevated [[CSF]] [[protein]] ([[oligoclonal bands]] with normal [[White blood cells|WBCs]])
* Slowed [[Nerve conduction study|motor nerve conduction velocities]]
* Prolonged distal [[Motor skill|motor]] latencies (period between F wave and initial stimulation)
* Delayed F wave latencies (recorded from the [[feet]], hence called "F" waves)
*[[MRI]] contrast enhancement and enlargement of [[Vertebra|T2]] [[spinal segments]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* EFNS/PNS criteria
* Koski criteria
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Corticosteroids]]
*[[Intravenous immunoglobulin]] ([[IVIG]])
*[[Immunosupressive drug|Immunosupressants]] ([[Alemtuzumab|Alemtuzemab]] [[Azathioprine]] [[Cyclophosphamide]] [[Cyclosporine|Cyclosporin]] [[Etanercept]] [[Interferon-alpha]])
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Multifocal motor neuropathy|Multifocal Motor Neuropathy]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Immune response|Abnormal immune response]] ([[Anti-ganglioside antibodies|Anti ganglioside]] [[Anti-ganglioside antibodies|GM-1]] [[IgM]] [[antibodies]])
| style="padding: 5px 5px; background: #F5F5F5;" |
* Progressive, asymmetric, distal and upper [[Limb (anatomy)|limb]] predominant weakness
* No significant [[sensory]] abnormalities
*[[Areflexia]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Elevated [[CSF]] [[protein]]
*
| style="padding: 5px 5px; background: #F5F5F5;" |
* Clinical criteria (EFNS/PNS):
** Slowly progressive or step-wise progressive, focal, asymmetric  [[limb]] weakness; i.e., [[Motor skill|motor]] involvement in the [[motor nerve]]  distribution of at least two nerves for  > 1 month.
** No objective [[Sensory system|sensory]]  abnormalities except  for minor vibration  sense abnormalities in  the [[lower limbs]]
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Intravenous immunoglobulin|Intravenous immunoglobulins]]
*[[Cyclophosphamide]]
*[[Rituximab]]
|-
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Organ System Involvement'''}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Differential Diagnosis'''}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Causes'''}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Features'''}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Laboratory Findings}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Gold Standard Test}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Therapy'''}}
|-
| rowspan="7" style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''''Organomegaly (Hepatosplenomegaly and Lymphadenopathy)'''''
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Malaria]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Plasmodium falciparum]]
*[[Plasmodium ovale|P. ovale]]
*[[P. malariae]]
*[[Plasmodium knowlesi|P. knowlesi]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Tertian ([[Plasmodium vivax|vivax]], [[Plasmodium ovale|ovale]], [[Plasmodium falciparum|falciparum]]), quartan (malariae), quotidian fever ([[Plasmodium knowlesi|knowlesi]])
*[[Vector]] is female [[Anopheles]] mosquito
*[[Hepatosplenomegaly]]
*[[Lymphadenopathy]]
*[[Jaundice]]
*[[Icterus (medicine)|Icterus]]
*[[Tachycardia]]
*[[Tachypnea]]
*[[Productive cough]]
*[[Hematuria]]
*[[Altered mental status]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Microcytic anemia]]
*[[Malaria differential diagnosis|Thick and thin blood films]] ([[Giemsa stain|Giemsa staining]])
 
* Rapid diagnostic test ([[antigen]] detection
*[[Polymerase chain reaction]] ([[Polymerase chain reaction|PCR]])
*[[Enzyme linked immunosorbent assay (ELISA)|Enzyme linked immunosorbent assay]] ([[Enzyme linked immunosorbent assay (ELISA)|ELISA]])
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Malaria differential diagnosis|Thick and thin films]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Non-[[Plasmodium falciparum|falciparum]] species:
**[[Chloroquine]] (in susceptible)
**[[Artemisinin]] plus [[Mefloquine|mefloquin]] or [[lumefantrine]] (in [[chloroquine]] resistant)
*[[Plasmodium falciparum|Falciparum]] species:
**[[Chloroquine]] (in susceptible)
**[[Artemether]] plus [[lumefantrine]] (in [[Chloroquine|chloroquin]] resistant) OR
**[[Artesunate]] plus [[Mefloquine|mefloquin]] OR
**[[Artesunate]] plus [[Sulfadoxine|sulfadoxine-pyrimethamine]]
**[[Atovaquone-Proguanil|Atovaquone plus proguanil]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Kala-azar]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Leishmaniasis|Leshmania donovani]]
* L. infantum
* L. chagasi
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Fever]]
* Vector is [[sandfly]]
*[[Hepatosplenomegaly]]
*[[Lymphadenopathy]]
*[[Hyperpigmentation]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Anemia]]
*[[Direct agglutination test]] (DAT)
* rk39 dipstick
*[[Enzyme linked immunosorbent assay (ELISA)|ELISA]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Splenic]] aspiration
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Liposomal amphotericin B]]
*[[Sodium stibogluconate]]
*[[Pentamidine]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Hepatitis|Infective Hepatitis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Hepatitis A virus|Hepatitis A virus (HAV)]]
*[[HBV]]
*[[Hepatitis C|HCV]]
*[[Hepatitis D|HDV]] (co-infection with [[HBV]])
*[[Hepatitis E|HEV]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Fever]]
* Transmitted via [[fecal-oral route]] ([[Hepatitis A|HAV]], [[Hepatitis B virus|HBV]], [[HDV]], [[HEV]]), infected sera ([[HCV]]), [[sexual contact]] with infected individuals
*[[Hepatosplenomegaly]] (may become shrunken in cases of [[cirrhosis]] due to chronic infection)
*[[Lymphadenopathy]]
*[[Jaundice]]
*[[Palmar erythema]]
*[[Spider angiomata]]
*[[Gynecomastia]]
*[[Arthritis-dermatitis syndrome]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Antigen]] and [[antibody]] detection
* Total and direct [[bilirubin]] (increased)
* Severe disease is often associated with persistent [[bilirubin]] levels >340 mmol/L
*[[ALT]] and [[AST]] (increased)
*[[Alkaline phosphatase]] (normal or mildly elevated)
*[[Prothrombin time]] (prolonged from synthetic defect, caused by hepatocellular [[necrosis]])
*[[Total protein]] (decreased)
*[[Globulin]] (mildly elevated)
* Initial [[lymphopenia]] and [[neutropenia]], followed by relative [[lymphocytosis]]
*[[Anemia|Low hemoglobin]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Antigen]] and [[antibody]] detection
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Interferon]] ([[IFN]])
 
*[[Antivirals|Nucleoside analogs]]
 
*[[Antivirals|Nucleotide analogs]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Chronic myelogenous leukemia|Chronic Myelogenous Leukemia]] (CML)'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Philadelphia chromosome|BCR/ABL gene]] fusion product due to [[Chromosomal translocation|translocation]] [[mutation]] [[Philadelphia chromosome|t(9;22)]](q34;q11)
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Fever]]
*[[Weight loss]]
*[[Hepatosplenomegaly]]
*[[Lymphadenopathy]]
 
*[[Bruises]]
*[[Petechiae]]
*[[Ulcers]]
*[[Vesicles]]
*[[Malaise]]
*[[Early satiety]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Anemia]]
 
*[[Leukocytosis]] (median of 100,000/µL) with a [[left shift]]
*[[Thrombocytosis]]
*[[Blast|Blasts]] usually <2%
* Absolute [[basophilia]]
* Absolute [[eosinophilia]]
*[[Monocytosis]]
*[[Thrombocytosis]]
*[[Thrombocytopenia]] suggests an alternative diagnosis or the presence of advanced stage
* Elevated [[uric acid]]
* Elevated [[histamine]] levels
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Fluorescence in situ hybridization|Fluoroscent insitu hybridization (FISH)]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Imatinib]]
*[[Dasatinib]]
*[[Nilotinib]]
*[[Bosutinib]]
*[[Ponatinib]]
 
*[[Cytarabine]]
*[[Cytarabine|HDAC]] (high-dose [[cytarabine]])
*[[Hydroxyurea]]
*[[Busulfan]]
*[[Busulfex]]
*[[Stem cell transplantation]]
 
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Lymphoma]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
* Various causes based on type:
**[[Hodgkin's lymphoma|Hodgkin's]]
**[[Non-Hodgkin lymphoma|Non-Hodgkin's]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Fever]]
*[[Weight loss]]
*[[Lymphadenopathy]]
*[[Hepatosplenomegaly]]
*[[Night sweats]], constant [[fatigue]]
* Purplish scaly rash in cases of [[cutaneous lymphoma]]
 
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Erythrocyte sedimentation rate|Elevated ESR]]
*[[C-reactive protein|Increased CRP]]
*[[Lactate dehydrogenase|Increased LDH]]
*[[Anemia of chronic disease]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Lymph node biopsy]]
| style="padding: 5px 5px; background: #F5F5F5;" |
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Primary amyloidosis|Primary (AL) Amyloidosis]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
* Aggregation and deposition of [[immunoglobulin light chains]] that are usually produced by [[plasma cell]] clones
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Nephrotic syndrome]] ([[peripheral edema]])
*[[Restrictive cardiomyopathy]] ([[fatigue]], [[dyspnea]], [[syncope]])
*[[Peripheral neuropathy]] ([[numbness]], [[tingling]])
*[[Hepatomegaly]] with elevated [[liver enzymes]]
*[[Macroglossia]]
*[[Purpura]]
*[[Bleeding diathesis]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Typical green birefringence under polarized light after Congo red staining (appears in red under normal light)
| style="padding: 5px 5px; background: #F5F5F5;" |
* Congo red staining
| style="padding: 5px 5px; background: #F5F5F5;" |
* Melphalan-prednisone/dexamethasone
* Dexamethasone plus Cyclophosphamide-thalidomide
* Stem cell transplantation
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Gaucher's disease|Gaucher's Disease]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[GBA (gene)|GBA gene]] [[mutation]]
* Aberrant metabolism of [[glucocerebroside]] ([[lipid]])
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Hydrops fetalis]]
* Dry, scaly skin ([[ichthyosis]]) or other [[skin]] abnormalities
*[[Hepatosplenomegaly]]
* Distinctive facial features
*[[Neurological disorder|Neurological problems]]
*[[Gall stones]]
*[[Growth retardation]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Hypocholesterolemia]]
*[[Splenic]] nodules
*[[Cytopenias]] (especially [[thrombocytopenia]])
* Increased [[ferritin]] levels
* Increased tartarate resistant acid phosphatase (TRAP) levels
| style="padding: 5px 5px; background: #F5F5F5;" |
* Enzyme assay for [[glucocerebrosidase]]
*[[DNA|DNA analysis]] for [[GBA (gene)|GBA mutation]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Enzyme replacement therapy|Enzyme replacement]]
*[[Splenectomy]]
*[[Blood transfusion]]
|-
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF| |'''Organ System Involvement'''}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Differential Diagnosis'''}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Causes'''}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Features'''}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Laboratory Findings}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Gold Standard Test}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Therapy'''}}
|-
| rowspan="5" style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''''Cardiac Failure'''''
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Cardiac amyloidosis (AL and ATTRwt)
| style="padding: 5px 5px; background: #F5F5F5;" |
* Monoclonal plasma cell proliferation
* Extracellular amyloid fibril deposition <br />
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
* Fatigue
* Dyspnea
* Dizziness
* Orthopnea
* Peripheral edema
* Weight loss due to cardiac cachexia
* Ascites
* Syncope on exertion
* Transthyretin (ATTRwt) associated more common in African-Americans during sixth to seventh decade of life
 
**
| style="padding: 5px 5px; background: #F5F5F5;" |
* Normocytic mormochromic anemia
* Serum free-light-chain assay positive
* Increased BNP, ANP and β2 microglobulin
* Voltage-to-mass ratio is more sensitive than EKG, 2D Echo and nuclear scanning alone <br />
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
* Biopsy:
 
* Diffuse deposition of amorphous hyaline material (nodular pattern - 8 to15 nm in diameter), in mesangium (weakly staining with periodic acid-Schiff (PAS)
 
<br />
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
* Supportive care
* Tafamidis
* Melphalan-prednisone/dexamethasone
* Dexamethasone plus Cyclophosphamide-thalidomide
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Hypertrophic obstructive cardiomyopathy]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Mutations|Mutation]] in sarcomeric protein (beta myosin heavy chain and myosin binding protein C)
*[[Autosomal dominant]] inheritance
 
*
*
| style="padding: 5px 5px; background: #F5F5F5;" |<br />
 
* [[Chest pain]] (also known as [[Angina pectoris|angina]])
* [[Dizziness]]
* [[Dyspnea]] ([[shortness of breath]]) which is due to increased stiffness of the [[hypertrophied left ventricle]]
* [[Exercise intolerance]]
* [[Fainting]], [[presyncope]] or frank [[syncope]], especially during exercise
* [[Fatigue]])
* [[Light-headedness]]
* [[Shortness of breath]]
* [[Reduced activity tolerance]]
* [[Shortness of breath]]
* [[Sudden cardiac death]]
 
<br />
 
**
**
| style="padding: 5px 5px; background: #F5F5F5;" |
* Increased [[Brain natriuretic peptide|BNP]]
* Increased [[creatine kinase]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Echocardiography:
** [[Left ventricular]] asymmetric hypertrophy
** Parasternal long axis shows relationship of the septal hypertrophy and the outflow tract
** Left ventricular diastolic dysfunction
** SAM (systolic anterior motion) of the mitral leaflet
** Mid-systolic closure of the aortic valve
** Late peaking, high velocity flow in the outflow tract
** Variability of obstruction with maneuvers (exercise, amyl nitrate inhalation, and post-PVC beats)  <br />
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Beta blockers]]
* [[Calcium channel blocker|Calcium channel blockers]]
* [[Septal myectomy]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Alcoholic cardiomyopathy]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Alcohol consumption
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Exercise intolerance]]
*[[Fainting]], [[presyncope]] or frank [[syncope]], especially during exercise
*[[Fatigue]])
*[[Light-headedness]]
*[[Shortness of breath]]
*[[Reduced activity tolerance]]
*[[Shortness of breath]]
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |<br />
 
* Elevated [[mean corpuscular volume]] ([[MCV]]) and [[mean corpuscular hemoglobin]] (MCHC)
* Mild [[thrombocytopenia]]
* Elevated [[LDH]], [[AST]], [[ALT]], [[creatine kinase]], malic dehydrogenase and alpha-hydroxybutyric dehydrogenase
* Elevated gammaglutamyl transpeptidase
* Serum concentrations of [[magnesium]] and [[zinc]] may be reduced
 
<br />
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Endomyocardial biopsy]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Restriction of dietary salt
* [[ACE inhibitor|ACE inhibitors]] or [[angiotensin II receptor blockers]]
* [[Beta blockers]]
* [[Diuretics]]
* [[Digoxin]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[ST elevation myocardial infarction|ST-elevation myocardial infarction]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Myocardial ischemia]]
* [[Atherosclerosis]]
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Exercise intolerance]]
*[[Fainting]], [[presyncope]] or frank [[syncope]], especially during exercise
*[[Fatigue]])
*[[Light-headedness]]
*[[Shortness of breath]]
*[[Reduced activity tolerance]]
*[[Shortness of breath]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Increased [[Cardiac troponin|cardiac troponins]]
* Increased [[Lactate dehydrogenase|LDH]]
* [[Leukocytosis]]
* [[ST segment elevation]] on EKG
| style="padding: 5px 5px; background: #F5F5F5;" |
* Elevation of [[Cardiac troponin|cardiac troponins]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Percutaneous coronary intervention or coronary artery bypass graft
* [[Aspirin]]
* [[Clopidogrel]]
* [[Beta blockers]]
* [[Diuretics]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |[[Pericarditis]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[HIV]]
* [[Dressler's syndrome]]
* [[Tuberculosis]]
* [[Uremia]]
* [[Radiation]]
* [[Malignancy]]
 
*
| style="padding: 5px 5px; background: #F5F5F5;" |
 
* [[Chest pain]] (relieved by sitting up and leaning forward and is worsened by lying down)
* [[Cough]] (either dry or productive)
* [[Fever]]
* [[Fatigue]]
* [[Anxiety]]
* [[Breathlessness]]
 
<br />
| style="padding: 5px 5px; background: #F5F5F5;" |
 
* [[Creatine kinase]]: [[Acute pericarditis]] may be associated with a modest increase in serum [[creatine kinase]]-MB (CK-MB) depending upon the extent of involvement of the underlying [[myocardium]].
* Increased [[Cardiac troponin I (cTnI) and T (cTnT)|cardiac troponin-I (cTnI)]]
* Increased [[LDH]]
* Increased serum [[myoglobin]]
* Increased [[SGOT]] ([[AST]])
 
<br />
| style="padding: 5px 5px; background: #F5F5F5;" |
* Two of the following four criteria:
** Pericarditic chest pain
** [[Pericardial rubs|Pericardial rub]]
** New widespread [[ST-segment elevation]] or [[PR depression]]
** New or worsening [[pericardial effusion]].
* Supporting findings can include elevation of inflammatory markers ([[C-reactive protein (CRP)|C-reactive protein]], [[Erythrocyte sedimentation rate|ESR]], [[white blood cell count]]), and evidence of pericardial inflammation on imaging([[Computed tomography|CT scan]] and [[cardiac MRI]]).
| style="padding: 5px 5px; background: #F5F5F5;" |
|-
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Organ System Involvement'''}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Differential Diagnosis'''}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Causes'''}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Features'''}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Laboratory Findings}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Gold Standard Test}}
| style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|'''Therapy'''}}
|-
| rowspan="4" style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''''Plasma Cell Dyscrasias'''''
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Multiple myeloma]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Chromosomal aberration|Chromosomal aberrations]] or other [[Genetics|genetic]] insults
*[[Malignant]] transformation of [[plasma cells]]
*Clonal [[plasma cell]] proliferation
| style="padding: 5px 5px; background: #F5F5F5;" |
*Diffuse [[bone]] pain and [[tenderness]] with [[osteolytic]] lesions
*[[Renal failure]]
*[[Hypercalcemia]]
*[[Anemia]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Anemia]]
*[[Thrombocytopenia]]
*[[Leukopenia]]
* Decreased albumin (reversed albumin:globulin ratio)
* Increased serum creatinine, urea
* Hypercalcemia
* Elevated ESR
* Normal-low alkaline phosphatase
* RBC rouleaux formation
* Bence-Jones proteins in urine
| style="padding: 5px 5px; background: #F5F5F5;" |
* Clonal plasma cells on bone marrow exam greater than equal to 10%
 
AND
 
* Any one of the following:
** Evidence of end-organ damage
** Hypercalcemia (>11 mg/dl)
** Renal insufficiency
** Anemia (Hb < 10 mg/dl)
** Bone lesions
** Greater than 1 lesions on MRI
| style="padding: 5px 5px; background: #F5F5F5;" |
*Induction [[chemotherapy]] with [[bortezomib]], [[lenalidomide]], and [[dexamethasone]]
*[[Bisphosphonates]]
*[[RANKL|RANK ligand]] inhibitors ([[denosumab]])
*[[Autologous bone marrow transplantation|Autologous stem cell transplantation]]
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Monoclonal gammopathy of undetermined significance]] ([[MGUS]])'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Chromosomal aberration|Chromosomal aberrations]] or other [[Genetics|genetic]] insults
*Clonal [[plasma cell]] proliferation
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Asymptomatic]]
*
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Serum]] [[M protein]] of <3 g/L
* Fewer than 10% [[plasma cells]] in the [[bone marrow]]
* No evidence of [[bone]] or [[Organ (anatomy)|organ]] damage
| style="padding: 5px 5px; background: #F5F5F5;" |
* Serum M protein (IgG or IgA) <3g/dl
 
AND
 
* Clonal bone marrow plasma cells < 10%
 
AND
 
* No end-organ damage
| style="padding: 5px 5px; background: #F5F5F5;" |
* Observation
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Multiple Myeloma|Asymptomatic Plasma Cell Myeloma]]'''
[[Multiple Myeloma|('''Smoldering''' and '''Indolent plasma cell myeloma''')]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Chromosomal aberration|Chromosomal aberrations]] or other [[Genetics|genetic]] insults
*[[Malignant]] transformation of [[plasma cells]]
*Clonal [[plasma cell]] proliferation
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Asymptomatic]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Serum]] [[M protein]] of  greater than equal to 3 g/L
* Greater than 10% [[plasma cells]] in the [[bone marrow]]
* No evidence of [[bone]] or [[Organ (anatomy)|organ]] damage
| style="padding: 5px 5px; background: #F5F5F5;" |
* Serum M protein (IgG or IgA greater than equal to 3 g/dl
 
OR
 
* Urinary M protein greater than equal to 500 mg/24 h
 
AND/OR
 
* Clonal bone marrow plasma cells 10-60%
 
AND
 
* No end-organ damage
| style="padding: 5px 5px; background: #F5F5F5;" |
* Observation
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Plasmacytoma]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Chromosomal aberration|Chromosomal aberrations]] or other [[Genetics|genetic]] insults
*[[Malignant]] transformation of [[plasma cells]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* Solitary bone [[plasmacytoma]] ([[bone]])
* Extramedullary [[plasmacytoma]] ([[Soft tissue|soft tissues]])
* Clinical manifestations related to [[tumor]] mass and compression [[symptoms]]
| style="padding: 5px 5px; background: #F5F5F5;" |
* On biopsy:
** Solitary infiltrate of clonal plasma cells in bone (SBP) or soft tissue (EMP).
** No evidence of infiltration by clonal plasma cells.
* Negative skeletal survey plus MRI/CT spine and pelvis except for the solitary lesion.
* Lack of hypercalcemia, renal insuffieciency, anemia, multiple bone lesions which would suggest MM
| style="padding: 5px 5px; background: #F5F5F5;" |
* Diagnosis of exclusion
| style="padding: 5px 5px; background: #F5F5F5;" |
* Radiotherapy
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |Skin Changes
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold; text-align:center;" |'''[[Scurvy]]'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Vitamin C]] deficiency
*[[Malabsorption]]
*[[Hemodialysis]]
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Gum disease]] such as gum [[bleeding]]
*Loose [[teeth]]
*Easy [[bruising]]
*Impaired [[immune]] response
*Impaired [[wound]] healing
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Vitamin C]] supplementation
*Citrus fruits
|}


==Epidemiology and Demographics==
==Epidemiology and Demographics==

Revision as of 04:29, 13 December 2019

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List of terms related to Lysozyme amyloid related amyloidosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]

Synonyms and keywords:Lysozyme amyloidosis, ALys, Hereditory amyloidosis, autosomal dominant amyloidosis, Hereditary lysozyme amyloidosis, Familial amyloid nephropathy due to lysozyme variant, Familial renal amyloidosis due to lysozyme variant, Hereditary amyloid nephropathy due to lysozyme variant, Hereditary renal amyloidosis due to lysozyme variant

Overview

Lysozyme amyloid related amyloidosis is one of the subtypes of familial amyloidosis, it is associated with four mutations include, Ile56Thr, Asp67His, Trp64Arg, and Phe57Ile. It is an extremely rare disease and it commonly affects individuals in their third to fourth decades of life. Manifestation of the disease are based on which organs are involved, and include GI symptoms, renal impairment, sicca syndrome, lymphadenopathy, splenomegaly, and petechiae or purpura. The diagnosis of lysozyme amyloid related amyloidosis is based on the family history, histologic examination and amino acid sequencing. There is no treatment for lysozyme amyloid related amyloidosis; the mainstay of therapy is supportive care. Organ transplant could be done as palliative treatment.

Historical Perspective

Classification

Lysozyme amyloid related amyloidosis is one of the subtypes of familial amyloidosis. Familiar amyloidosis may be classified according to the type of mutant protein into 6 subtypes:[5][6][7]

 
 
 
 
 
 
 
 
 
 
 
 
 
Familial amyloidosis subtypes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Transthyretin (TTR)
 
Apolipoprotein AI
 
Gelsolin
 
Lysozyme
 
Cystatin C
 
Fibrinogen Aa-chain
 
Apolipoprotein AII

Pathophysiology

Genetics

There are four genetic mutations which are associated with lysozyme amyloid related amyloidosis. include:[4]

  • Ile56Thr
  • Asp67His
  • Trp64Arg
  • Phe57Ile

Causes

Common cause of lysozyme amyloid related amyloidosis is genetic mutations.[13][5][6][14]

Differentiating lysozyme amyloid related amyloidosis from Other Diseases

Lysozyme amyloid related amyloidosis must be differentiated from other types of familial amyloidosis and other diseases that mimic amyloidosis and may present as organ dysfunction, specifically, nephrotic syndrome leading to renal failure, cardiac failure and polyneuropathy. For more information on the differential diagnosis of lysozyme amyloid related amyloidosis click here

Epidemiology and Demographics

  • Lysozyme amyloid related amyloidosis commonly affects individuals in their third to fourth decades of life.[5]

Risk Factors

The most potent risk factor in the development of lysozyme amyloid related amyloidosis is positive familial history. Other risk factors include older age, male gender, and African-American race.[17][3][18]

Screening

There is insufficient evidence to recommend routine screening for lysozyme amyloid related amyloidosis.

Natural History, Complications, and Prognosis

Note: Because the risk of bleeding in this patients, liver biopsy should not be performed in suspected ones.[20]

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Physical examination of patients with lysozyme amyloid related amyloidosis is usually remarkable for renal impairment, petechiae, purpura, lymphadenopathy, and splenomegaly.[26][24][4][25][27][28]

Laboratory Findings

  • Common tests that are abnormal in renal function tests including serum creatinine, urinary protein, glomerular filtration rate, and albumin to creatinine ratio in the urine.

Electrocardiogram

Although, cardiac involvement is so rare in lysozyme amyloid related amyloidosis, electrocardiography may be done for cardiac analysis..

X-ray

There are no x-ray findings associated with lysozyme amyloid related amyloidosis.

Echocardiography or Ultrasound

Although, cardiac involvement is so rare in lysozyme amyloid related amyloidosis, echocardiography may be done for cardiac analysis.

CT scan

There are no CT scan findings associated with lysozyme amyloid related amyloidosis.

MRI

There are no MRI findings associated with lysozyme amyloid related amyloidosis.

Other Imaging Findings

Total body SAP component scintigraphy may be helpful in the diagnosis of lysozyme amyloid related amyloidosis. It can show lysozyme amyloid deposition and extension of it in the liver, spleen, kidney, adrenal glands, and bone marrow.[19]

Other Diagnostic Studies

Treatment

Medical Therapy

There is no treatment for lysozyme amyloid related amyloidosis; the mainstay of therapy is supportive care.[32]

Surgery

Primary Prevention

There are no established measures for the primary prevention of lysozyme amyloid related amyloidosis.

Secondary Prevention

Effective measures for the secondary prevention of lysozyme amyloid related amyloidosis include:[19]

References

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  2. 2.0 2.1 Sipe JD, Cohen AS (June 2000). "Review: history of the amyloid fibril". J. Struct. Biol. 130 (2–3): 88–98. doi:10.1006/jsbi.2000.4221. PMID 10940217.
  3. 3.0 3.1 3.2 Khan MF, Falk RH (November 2001). "Amyloidosis". Postgrad Med J. 77 (913): 686–93. PMC 1742163. PMID 11677276.
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  7. Scriver, Charles (2001). The metabolic & molecular bases of inherited disease. New York: McGraw-Hill. ISBN 978-0079130358.
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  14. Scriver, Charles (2001). The metabolic & molecular bases of inherited disease. New York: McGraw-Hill. ISBN 978-0079130358.
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  17. 17.0 17.1 Shin YM (March 2011). "Hepatic amyloidosis". Korean J Hepatol. 17 (1): 80–3. doi:10.3350/kjhep.2011.17.1.80. PMC 3304630. PMID 21494083.
  18. Shin YM (March 2011). "Hepatic amyloidosis". Korean J Hepatol. 17 (1): 80–3. doi:10.3350/kjhep.2011.17.1.80. PMC 3304630. PMID 21494083.
  19. 19.0 19.1 19.2 19.3 19.4 Granel, Brigitte; Valleix, Sophie; Serratrice, Jacques; Chérin, Patrick; Texeira, Antonio; Disdier, Patrick; Weiller, Pierre-Jean; Grateau, Gilles (2006). "Lysozyme Amyloidosis". Medicine. 85 (1): 66–73. doi:10.1097/01.md.0000200467.51816.6d. ISSN 0025-7974.
  20. Harrison, R F; Hawkins, P N; Roche, W R; MacMahon, R F; Hubscher, S G; Buckels, J A (1996). "'Fragile' liver and massive hepatic haemorrhage due to hereditary amyloidosis". Gut. 38 (1): 151–152. doi:10.1136/gut.38.1.151. ISSN 0017-5749.
  21. Lim AY, Lee JH, Jung KS, Gwag HB, Kim DH, Kim SJ, Lee GY, Kim JS, Kim HJ, Lee SY, Lee JE, Jeon ES, Kim K (July 2015). "Clinical features and outcomes of systemic amyloidosis with gastrointestinal involvement: a single-center experience". Korean J. Intern. Med. 30 (4): 496–505. doi:10.3904/kjim.2015.30.4.496. PMC 4497337. PMID 26161016.
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  24. 24.0 24.1 Gillmore, Julian D.; Booth, David R.; Madhoo, S.; Pepys, Mark B.; Hawkins, Philip N. (1999). "Hereditary renal amyloidosis associated with variant lysozyme in a large English family". Nephrology Dialysis Transplantation. 14 (11): 2639–2644. doi:10.1093/ndt/14.11.2639. ISSN 1460-2385.
  25. 25.0 25.1 Yood, Robert A. (1983). "Bleeding Manifestations in 100 Patients With Amyloidosis". JAMA: The Journal of the American Medical Association. 249 (10): 1322. doi:10.1001/jama.1983.03330340064034. ISSN 0098-7484.
  26. J. G. Lanham, M. L. Meltzer, F. C. De Beer, G. R. Hughes & M. B. Pepys (1982). "Familial amyloidosis of Ostertag". The Quarterly journal of medicine. 51 (201): 25–32. PMID 7111672.
  27. Segalov, Eva; Gibson, John; Joshua, Douglas E.; Kronenberg, Harry (2009). "Primary Amyloidosis Co-Presenting with Cervical and Massive Intra-Abdominal Lymphadenopathy". Leukemia & Lymphoma. 19 (5–6): 519–520. doi:10.3109/10428199509112215. ISSN 1042-8194.
  28. "Familial Nephropathic Non-neuropathic Amyloidosis: Clinical Features, Immunohistochemistry and Chemistry". QJM: An International Journal of Medicine. 1991. doi:10.1093/oxfordjournals.qjmed.a068643. ISSN 1460-2393.
  29. Merlini G, Seldin DC, Gertz MA (May 2011). "Amyloidosis: pathogenesis and new therapeutic options". J. Clin. Oncol. 29 (14): 1924–33. doi:10.1200/JCO.2010.32.2271. PMC 3138545. PMID 21483018.
  30. Real de Asúa D, Costa R, Galván JM, Filigheddu MT, Trujillo D, Cadiñanos J (2014). "Systemic AA amyloidosis: epidemiology, diagnosis, and management". Clin Epidemiol. 6: 369–77. doi:10.2147/CLEP.S39981. PMC 4218891. PMID 25378951.
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  32. Pleyer, Christopher; Flesche, Jan; Saeed, Fahad (2015). "Lysozyme amyloidosis – a case report and review of the literature". Clinical Nephrology Case Studies. doi:10.5414/CNCS108538. ISSN 2196-5293.
  33. Yazaki, Masahide; Farrell, Sandra A.; Benson, Merrill D. (2003). "A novel lysozyme mutation Phe57Ile associated with hereditary renal amyloidosis". Kidney International. 63 (5): 1652–1657. doi:10.1046/j.1523-1755.2003.00904.x. ISSN 0085-2538.
  34. Valleix, Sophie; Drunat, Séverine; Philit, Jean-Baptiste; Adoue, Daniel; Piette, Jean-Charles; Droz, Dominique; MacGregor, Brigitte; Canet, Denis; Delpech, Marc; Grateau, Gilles (2002). "Hereditary renal amyloidosis caused by a new variant lysozyme W64R in a French family". Kidney International. 61 (3): 907–912. doi:10.1046/j.1523-1755.2002.00205.x. ISSN 0085-2538.
  35. Sattianayagam, P. T.; Gibbs, S. D. J.; Rowczenio, D.; Pinney, J. H.; Wechalekar, A. D.; Gilbertson, J. A.; Hawkins, P. N.; Lachmann, H. J.; Gillmore, J. D. (2012). "Hereditary lysozyme amyloidosis - phenotypic heterogeneity and the role of solid organ transplantation". Journal of Internal Medicine. 272 (1): 36–44. doi:10.1111/j.1365-2796.2011.02470.x. ISSN 0954-6820.
  36. Loss, Martin; Ng, Wa S.; Karim, Rooshdiya Z.; Strasser, Simone I.; Koorey, David J.; Gallagher, Peter J.; Verran, Deborah J.; McCaughan, Geoffrey W. (2006). "Hereditary lysozyme amyloidosis: Spontaneous hepatic rupture (15 years apart) in mother and daughter. role of emergency liver transplantation". Liver Transplantation. 12 (7): 1152–1155. doi:10.1002/lt.20803. ISSN 1527-6465.


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