Sandbox:Sahar

Amyloisosis subtype	Protein	Involved organs severity	Involved organs severity	Amyloisosis subtype
Amyloisosis subtype	Amyloisosis subtype	Amyloisosis subtype	Amyloisosis subtype	Amyloisosis subtype
Primary	_	Anemia	MRI is the best radiologic tool to differentiate between retroperitoneal masses.
Secondary	✔	Leukocytosis, positive inflammatory markers
DRA (dialysis related amyloidosis)	✔	positive tumor marker
Senile systemic (cardiac) amyloidosis	_	DM type II, amylase and lipase levels may be slightly elevated
Meretoja syndrome

Infection/Inflammation

Increased production of IL-1/IL-6/TNF-α

Upregulation of hepatic serum amyloid A production

SAA production uptake by macrophages

C-terminal cleavage of SAA

β-sheet configuration of SAA

Fibril deposition in extracellular space

Binding of glycosaminoglycan, serum amyloid P, and lipid components

Resistant to proteolysis

The above algorithm is adopted from International Journal of Nephrology and Renovascular Disease

Associated Conditions
Conditions	Examples
Chronic infections	Tuberculosis Leprosy Whipple Disease Osteomyelitis Chronic pyelonephritis Subacute bacterial endocarditis Chronic cutaneous ulcers
Monogenic periodic fever syndromes	TNF Receptor associated periodic syndrome (TRAPS) Cryopyrin-associated periodic fever syndrome Mevalonate kinase deficiency Familial mediterranean fever
Conditions predisposing to recurrent infections	Cystic fibrosis Bronchiectasis Kartagener syndrome Epidermolysis bullosa Injected drug abuse Jejuno-ileal bypass Paraplegia Sickle cell anemia Immunodeficiency Common variable immunodeficiency Cyclic neutropenia Hyperimmunoglobulin M syndrome Hypogammaglobulinemia Sex-linked agammaglobulinemia Human immunodeficiency virus/AIDS
Neoplasia	Adenocarcinoma Basal cell carcinoma Carcinoid tumor Castleman disease Gastrointestinal stromal tumor Hairy cell leukemia Hepatic adenoma Hodgkin disease Mesothelioma Renal cell carcinoma Sarcoma
Inflammatory Arthritis	Adult-onset Still disease Ankylosing spondylitis Juvenile idiopathic arthritis Psoriatic arthropathy Reiter syndrome Rheumatoid arthritis Gout
Systemic Vasculitis	Antineutrophil cytoplasmic antibody-associated vasculitis Behcet disease Giant cell arteritis Polyarteritis nodosa Polymyalgia rheumatica Systemic lupus erythematosus Takayasu arteritis Inflammatory Bowel Disease Ulcerative colitis Crohn disease
Others	Atrial myxoma Inflammatory abdominal aortic aneurism Retroperitoneal fibrosis SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome Sarcoidosis Sinus histiocytosis with massive lymphadenopathy

Organ System Involvement	Differential Diagnosis	Causes	Clinical Features	Laboratory Findings	Gold Standard Test	Therapy
Nephrotic Syndrome and Renal Failure	Secondary (AA) Amyloidosis	Chronic inflammatory disorders Chronic infections	Periorbital edema Lower extremity edema Signs/symptoms of underlying inflammatory disorder	Proteinuria Elevated level of acute phase reactant due to underlying inflammatory condition	Biopsy and congo-red staining of the sample	Treatment of the undelying iflammatory disorder
	Primary (AL) Amyloidosis	Monoclonal plasma cell proliferation Extracellular amyloid fibril deposition	Anasarca Bleeding tendency Swelling of lower limbs Frothy urine Chest pain Numbness or tingling Early satiety Joint pains Enlarged tongue Taste loss Hoarseness of voice Hair loss	Increased erythrocyte sedimentation rate (ESR) Increased alanine aminotrasnferase (ALT) and aspartate aminotrasnferase (AST) Increased cardiac troponins Increased brain natriuretic peptide (BNP) Increased blood urea nitrogen (BUN) and creatinine Proteinuria Urinary hyaline and fatty casts Hypercholesterolemia	Biopsy: Diffuse glomerular deposition of amorphous hyaline material (nodular pattern - 8 to15 nm in diameter), in mesangium (weakly staining with periodic acid-Schiff (PAS)	Melphalan-prednisone/dexamethasone Dexamethasone plus Cyclophosphamide-thalidomide Stem cell transplantation Kidney transplantation
	Diabetic Nephropathy	Hyperfiltration Constriction of efferent arteriole Microalbuminuria Mesangial proliferation	Nocturia Fatigue Pruritis Peripheral edema	Hyperglycemia (random plasma glucose ≥200 mg/dL) Proteinuria Glucosuria HbA1C ≥6.5% (48 mmol/mol).	Biopsy: PAS positive Kimmelstiel-Wilson nodules Glomerulosclerosis	ACE inhibitors Angiotensin receptor blockers Glycemic control
	Minimal Change Disease	Upper respiratory tract infection Allergy to bee sting NSAID Gold Penicillamine Ampicillin Mercury Hodgkin's and non-Hodgkin's lymphoma	Peripheral edema Hypertension Peripheral edema	Proteinuria Hypertension Hyperlipidemia Hypoalbuminemia Microscopic hematuria	Biopsy: Fused podocytes/effacement	Prednisone with taper ACE inhibitors Angiotensin receptor blockers Salt restriction
	Focal Segmental Glomerulosclerosis	HIV Parvovirus B19 Cytomegalovirus Heroin Interferon alpha Lithium Pamidronate/aledronate Anabolic steroids Diabetes mellitus Hypertension Obesity Cyanotic congenital heart disease Sickle cell anemia	Peripheral edema Hypertension Peripheral edema	Proteinuria Hypertension Hyperlipidemia Hypoalbuminemia Microscopic hematuria	Biopsy: Podocyte foot process effacement Capillary lumen abolished by the segmental increase in matrix	Prednisone Calcineurin inhibitors (Cyclosporin, tacrolimus) Rituximab Cyclophosphamide/chlorambucil Mycophenolate motefil
	Fabry's Disease	Deficient alpha galactosidase A	Abdominal pain Arthralgia Febrile episodes Angiokeratomas Burning pain and tingling (peripheral neuropathy) Hypohidrosis X-linked recessive inheritance	Deficient alpha galactosidase A Increased ceramide trihexoside (globotriaosylceramide)	Alpha-galactosidase A activity GLA gene analysis for heterozygotes	Enzyme replacement therapy ACE inhibitors Gabapentin, carbamazepine Migalastat
	Light Chain Deposition Disease	Multiple myeloma Waldenström's macroglobulinemia Monoclonal gammopathy of undetermined significance	Asymptomatic Fatigue Weight loss Dyspnea Peripheral edema	Proteinuria Portal hypertension Increased ALT, AST	Biopsy: Non-amyloid granules	Bortezomib Autologous stem cell transplantation Immunomodulatory drugs Kidney transplant
	Membranous Glomerulonephritis	Hepatitis B and C HIV Non-Hodgkin`s lymphoma Chronic lymphocytic leukemia Hodgkin`s lymphoma Solid tissue tumors Schistosomiasis Leprosy Hydatid disease Loaiasis (filaria) Quartan malaria Systemic lupus erythematosis (SLE)	Headache Edema affecting any area of the body Foamy appearance of urine Weight gain Poor appetite Nocturia Fatigue Hematuria	Proteinuria Hypertension Hyperlipidemia Hypoalbuminemia Microscopic or gross hematuria Hypoalbuminemia ANA and anti-dsDNA positivity	Biopsy: IgG and C3 deposits with thickened basement membrane with spikes and vacuolization Glomerulosclerosis	Prednisone Methylprednisolone with cyclophosphamide Tacrolimus with a six-month taper Rituximab
	Fibrillary-Immunotactoid Glomerulopathy	Idiopathic Hepatitis C	Microscopic or gross hematuria	Proteinuria Hypertension Increased blood urea nitrogen (BUN) and creatinine	Biopsy: Polycloncal IgG deposits Infiltration of glomerular structures by amorphous acellular material (nonbranching fibrils 12-24nm in diameter) Ig heavy-chain and one light-chain subclass
Organ System Involvement	Differential Diagnosis	Causes	Clinical Features	Laboratory Findings	Gold Standard Test	Therapy
Polyneuropathy	POEMS syndrome (Demyelinating)	Monoclonal plasma cell proliferation Cytokine storm (IL-1, IL-6, IL-12, TNF alpha, VEGF)	Symmetrical, ascending chronic progressive polyneuropathy with both sensory (pin-prick and vibration) and motor disability (motor > sensory) Generalized/extermity pain Areflexia	Increased number of thrombocytes Increased number of erythrocytes Elevated cerebrospinal fluid (CSF) protein content Increased number of leukocytes High levels of IgG lambda or IgA lambda M-protein in the serum Increased number of plasma cells in the bone marrow Increased serum VEGF level Elevated levels of antitiroglobulin antibody and antithyroid peroxydase antibody	International Myeloma Working Group (IMWG) clinical and laboratory diagnostic criteria
	Metabolic Syndrome (Axonal pathology)	Diabetes mellitus	Symmetric sensorimotor distal polyneuropathy Asymmetric proximal neuropathy 3rd nerve palsy Carpel tunnel syndrome Autonomic neuropathy "Glove and stocking" type pain Muscle wasting Hammer toes Polyuria Polydipsia	Uncontrolled hyperglycemia Slowed nerve conduction Small fiber dysfunction Monofilament testing	Fasting blood sugar level greater than equal to 126 mg/dl on 2 separate occasions	Anti-diabetic therapy Gabapentin Carbamazepine Foot care
	Vitamin Deficiencies (Axonal Pathology)	Vitamin B12 deficiency (Decreased S-adenosyl methionine) Vitamin B1 deficiency	Primarily sensory deficits Vibration and proprioception affected Gait abnormalities Cognitive impairment Irritability Glossitis	Anemia (megaloblastic in case of B12 deficiency) Decreased serum Vitamin B12 levels (< 200 pg/ml) Elevated methylmalonic acid	Serum Vitamin B12 levels Methylmalonic acid levels Intrinsic factor antibodies	Vitamin B12 supplement (parenteral)
	Guillain-Barre Syndrome (Demyelinating)	Anti-ganglioside and anti-myelin antibodies Viral infections: Epstein Barr virus HIV Cytomegalovirus Varicella Zoster virus Bacterial infections: Campylobacter infection Mycoplasma pneumoniae	Rapid onset and quick progression Progression stops after 2-3 weeks Bilateral ascending paraesthesias and paralysis (generalized) 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	Delayed F waves	Clinical diagnostic criteria (progressive weakness of more than two limbs, areflexia, and progression for no more than four weeks)	Intravenous immunoglobulins Plasma exchange Respiratory support DVT/PE prevention
	Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (Mixed axonal and demyelinatiing)	Abnormal immune response (both IgG based humoral and T-Cell mediated) response to unknown antigen (possible culprits include myelin proteins P0, P2 and PMP22)	Slow onset and gradual progression Relapsing and remitting course Symmetrical proximal and distal motor and sensory weakness (legs>arms) Foot drop Numbness, tingling and pain Areflexia	Elevated CSF protein (oligoclonal bands with normal WBCs) Slowed motor nerve conduction velocities Prolonged distal 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 T2 spinal segments	EFNS/PNS criteria Koski criteria	Corticosteroids Intravenous immunoglobulin (IVIG) Immunosupressants (Alemtuzemab Azathioprine Cyclophosphamide Cyclosporin Etanercept Interferon-alpha)
	Multifocal Motor Neuropathy	Abnormal immune response (Anti ganglioside GM-1 IgM antibodies)	Progressive, asymmetric, distal and upper limb predominant weakness No significant sensory abnormalities Areflexia	Elevated CSF protein	Clinical criteria (EFNS/PNS): Slowly progressive or step-wise progressive, focal, asymmetric limb weakness; i.e., motor involvement in the motor nerve distribution of at least two nerves for > 1 month. No objective sensory abnormalities except for minor vibration sense abnormalities in the lower limbs	Intravenous immunoglobulins Cyclophosphamide Rituximab
Organ System Involvement	Differential Diagnosis	Causes	Features	Laboratory Findings	Gold Standard Test	Therapy
Organomegaly (Hepatosplenomegaly and Lymphadenopathy)	Malaria	Plasmodium falciparum P. ovale P. malariae P. knowlesi	Tertian (vivax, ovale, falciparum), quartan (malariae), quotidian fever (knowlesi) Vector is female Anopheles mosquito Hepatosplenomegaly Lymphadenopathy Jaundice Icterus Tachycardia Tachypnea Productive cough Hematuria Altered mental status	Microcytic anemia Thick and thin blood films (Giemsa staining) Rapid diagnostic test (antigen detection Polymerase chain reaction (PCR) Enzyme linked immunosorbent assay (ELISA)	Thick and thin films	Non-falciparum species: Chloroquine (in susceptible) Artemisinin plus mefloquin or lumefantrine (in chloroquine resistant) Falciparum species: Chloroquine (in susceptible) Artemether plus lumefantrine (in chloroquin resistant) OR Artesunate plus mefloquin OR Artesunate plus sulfadoxine-pyrimethamine Atovaquone plus proguanil
	Kala-azar	Leshmania donovani L. infantum L. chagasi	Fever Vector is sandfly Hepatosplenomegaly Lymphadenopathy Hyperpigmentation	Anemia Direct agglutination test (DAT) rk39 dipstick ELISA	Splenic aspiration	Liposomal amphotericin B Sodium stibogluconate Pentamidine
	Infective Hepatitis	Hepatitis A virus (HAV) HBV HCV HDV (co-infection with HBV) HEV	Fever Transmitted via fecal-oral route (HAV, 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	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 Low hemoglobin	Antigen and antibody detection	Interferon (IFN) Nucleoside analogs Nucleotide analogs
	Chronic Myelogenous Leukemia (CML)	BCR/ABL gene fusion product due to translocation mutation t(9;22)(q34;q11)	Fever Weight loss Hepatosplenomegaly Lymphadenopathy Bruises Petechiae Ulcers Vesicles Malaise Early satiety	Anemia Leukocytosis (median of 100,000/µL) with a left shift Thrombocytosis 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	Fluoroscent insitu hybridization (FISH)	Imatinib Dasatinib Nilotinib Bosutinib Ponatinib Cytarabine HDAC (high-dose cytarabine) Hydroxyurea Busulfan Busulfex Stem cell transplantation
	Lymphoma	Various causes based on type: Hodgkin's Non-Hodgkin's	Fever Weight loss Lymphadenopathy Hepatosplenomegaly Night sweats, constant fatigue Purplish scaly rash in cases of cutaneous lymphoma	Elevated ESR Increased CRP Increased LDH Anemia of chronic disease	Lymph node biopsy
	Primary (AL) Amyloidosis	Aggregation and deposition of immunoglobulin light chains that are usually produced by plasma cell clones	Nephrotic syndrome (peripheral edema) Restrictive cardiomyopathy (fatigue, dyspnea, syncope) Peripheral neuropathy (numbness, tingling) Hepatomegaly with elevated liver enzymes Macroglossia Purpura Bleeding diathesis	Typical green birefringence under polarized light after Congo red staining (appears in red under normal light)	Congo red staining	Melphalan-prednisone/dexamethasone Dexamethasone plus Cyclophosphamide-thalidomide Stem cell transplantation
	Gaucher's Disease	GBA gene mutation Aberrant metabolism of glucocerebroside (lipid)	Hydrops fetalis Dry, scaly skin (ichthyosis) or other skin abnormalities Hepatosplenomegaly Distinctive facial features Neurological problems Gall stones Growth retardation	Hypocholesterolemia Splenic nodules Cytopenias (especially thrombocytopenia) Increased ferritin levels Increased tartarate resistant acid phosphatase (TRAP) levels	Enzyme assay for glucocerebrosidase DNA analysis for GBA mutation	Enzyme replacement Splenectomy Blood transfusion

Example #1

The patient presented with S.O.B. one year after hysterectomy for a leiomyomatous uterus.

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  CT in Intravenous leiomyomatosis

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