Antiphospholipid Syndrome (APS)
APS is a rare autoimmune disorder characterized by recurring blood clots resulting from antibodies formed against phospholipids
• Blood clots can form in arteries, veins, or microvasculature
Antiphospholipid antibodies (aPL):
• Lupus anticoagulant (LA)
• Anticardiolipin antibodies (aCL)
• Anti-ß2 glycoprotein I antibodies (aß2-GPl)
The origin of these antibodies is unknown
Diagnosis of APS - Presence of at least:
• 1 clinical event (confirmed venous, arterial, or small-vessel thrombosis)
• 1 of the three aPLs measured on 2 or more occasions 12 weeks apart
For patients to be diagnosed with APS, presence of 1 clinical event and presence of one of the antibodies have to be present
Treatment (EULAR Guidelines):
• Anticoagulation with warfarin is recommended; INR target 2-3
• If patient has an arterial/venous event while on warfarin and INR target 2-3 was achieved; it's reasonable to increase INR target to 3-4
• DOACs are currently not recommended in APS
Mirna Guirguis, PharmD @mirna_guirguis
#Antiphospholipid #Syndrome #APS #diagnosis #management #anticoagulation #guidelines
Antiphospholipid Syndrome (APLS) Testing - Hypercoagulable Workup Algorithm
INDICATIONS FOR TESTING:
• Vascular thrombosis
- 1 or more clinical episodes of arterial, venous, or small-vessel thrombosis
• Unexplained pregnancy loss defined as:
- 1 or more unexplained deaths of a morphologically normal fetus beyond the 10th week of gestation
- 1 or more premature births of a morphologically normal neonate before the 34th week of gestation due to eclampsia, preeclampsia, or placental insufficiency
- 3 or more unexplained, consecutive, spontaneous abortions before the 10th week of gestation, and with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded
Testing:
• Lupus Anticoagulant Reflexive Panel
• Cardiolipin Antibodies, IgG and IgM
• Beta-2 Glycoprotein 1 Antibodies, IgG and IgM
• Phosphatidylserine and Prothrombin Antibodies, IgG and IgMa
• Phosphatidylserine Antibodies, IgG and IgMa
• Prothrombin Antibody, IgGa
• Cardiolipin Antibody, IgA
• Beta-2 Glycoprotein 1 Antibody, IgA
ARUPConsult @ARUPLabs
#APLS #Antiphospholipid #Syndrome #Hypercoagulable #Workup #Algorithm #diagnosis #hematology
Primary Adrenal Insufficiency
Addison's Disease - Damage of the adrenal glands with lack of cortisol, androgens and aldosterone
Causes of Adrenal Insufficiency:
Most Common Causes:
• Autoimmune > Tuberculosis
Infiltrative Disorders:
• Infection (tuberculosis, fungal infections)
- Tuberculosis: can cause adrenal calcification and enlargement
• Sarcoidosis
• Lymphoma
Metastatic Disease -> Adrenals:
• Lung cancer
• Renal cell carcinoma, and melanoma
Bilateral Adrenal Hemorrhage:
• Consider if unexpected hypotension develops
• Risk factors for BAH include protein C deficiency, anticoagulation, DIC and sepsis
- (Neisseria meningitidis, H Flu, pneumococci, pseudomonas)
Autoimmune: + 21-Hydroxylase Antibodies:
• 50% will develop another autoimmune endocrine disorder
- Primary hypothyroidism
- Primary ovarian insufficiency
- Celiac disease,
- Hypoparathyroidism
- Type 1 diabetes mellitus
Aldosterone Deficiency:
Symptoms:
• Salt craving
• Dizziness
• Nausea/vomiting
• Fatigue
Signs:
• Orthostasis
• Hypotension
Labs:
• ↑ PRA
• ↓ Serum sodium
• ↑ Serum potassium
• ↑ H+ (NAGMA from RTA type IV)
Cortisol Deficiency:
Symptoms:
• Fatigue
• Weakness
• Low-grade fever
• Weight loss
• Anorexia
• Nausea/vomiting
• Abdominal pain
• Back pain
• Arthralgia
• Myalgia
Cortisol Deficiency: Signs
• Hyperpigmentation ("bronzing")
- Palmar creases
- Extensor surfaces
- Buccal mucosa
- *Not present in approximately 5% patients
• ↓ BP
• ↓ Serum cortisol
• ↑ Plasma ACTH
• ↓ Serum sodium
• ↓ Plasma glucose
• ↑ Eosinophils (Not always present)
↓ DHEA/Androgens:
• Symptoms: Reduced libido
• Signs: Decreased axillary or pubic hair
• Labs: ↓ Serum DHEAS
Diagnosis:
• History and physical:
- Symptoms/physical exam.
- Dark patches on the skin might be a clue
• Blood tests:
- Check sodium, potassium, AM cortisol and ACTH
- + 21-hydroxylase antibodies are found in approximately 90% of autoimmune adrenalitis cases
- Serum cortisol < 3 ug/dL -> Primary AI present
- ACTH stimulation test: Administer 250 mcg ACTH. Measure at 0, 30, and 60 mins.
- Check Serum Cortisol. IF < 18 ug/dL Primary AI present
- ACTH test is not affected by use of DEXAMETHASONE
- ACTH test is affected by HYDROCORTISONE
#Primary #adrenal #insufficiency #addisons #disease #endocrinology #diagnosis #signs #symptoms
Sjogren's Syndrome Overview
Epidemiology:
• F > M: 9:1
• 5-6th Decades (can be any age)
Autoimmune exocrinopathy multisystemic disease affecting salivary and lacrimal glands:
• Focal lymphocytic sialadenitis
• Keratoconjunctivitis sicca
• Xerostomia
• Symmetric parotid swelling
• Lacrimal swelling
• Skin dryness
• Vaginal dryness
• Primary form: not associated with other diseases
• Secondary form: overlaps with RA, SLE
• Mikulicz syndrome: Prominent parotid and lacrimal glandular enlargement
Sjogren's Syndrome Diagnosis:
• Dry eyes
• Salivary hypofunction
• Antibodies: Anti-Ro/SSA & Anti-La/SSB ab
• Lip (minor salivary gland) biopsy
• Ocular examination
Labs:
• Antibodies:
• Anti-Ro/SSA ab (specific in primary)
• Anti-La/SSB ab
• RF
• Antinuclear antibodies ≥ 1:320
• Cytopenia: 2%
• Hypocomplementemia
• Can cause TYPE IV RTA, TYPE I RTA
Diagnosis:
• LIP (minor salivary gland) biopsy
• Histo: aggregate foci (>50 cells/aggregate) of CD4 T cells, B cells, and plasma cells around salivary ducts
Clinical Features:
HEENT:
• Keratoconjunctivitis sicca
• Xerostomia
• Dental caries
• Parotid swelling
CNS Involvement:
• Central nervous system (CNS): demyelinating disease, myelopathy, cranial nerve neuropathy
• Peripheral nervous system: small-fiber neuropathy, mononeuritis multiplex, peripheral neuropathy, transverse myelitis
• 8%-27% for CNS and peripheral
Thyroid Disease:
• 10%-15%
Pulmonary
• Interstitial Pneumonitis (LIP, UIP, NSIP):
• Lymphocytic interstitial pneumonia
• Usual interstitial pneumonia
• Tracheobronchial disease
• Xerotrachea
• NSIP: Pleural thickening or effusion, INC risk PE, Pulmonary amyloidosis, PAH
Skin:
• Dry skin (xerosis)
• Cutaneous vasculitis: 10%-16%
Liver:
• Autoimmune hepatitis, primary biliary cirrhosis: 3%-20%
Renal:
• Interstitial nephritis
• Distal (Type I) renal tubular acidosis
• NAGMA
• Glomerulonephritis: 5%-6%
• Membranoproliferative GN
• Nephrogenic DI
Hematologic:
• Lymphoma, Cytopenia: 2%
Systemic Vasculitis:
• 7%, Cryoglobulinemia (4%-12%), Raynaud phenomenon (16%)
MSK:
• Arthralgia and Arthritis
Malignancy Risk:
• Non-Hodgkins lymphoma
• B cell lymphoma
• Large B cell lymphoma
• MALT Lymphoma
• Lung Adenocarcinoma
Treatment:
• Symptomatic: artificial tears/artificial saliva/mouth lubricants
• Pharmacologic:
• Severe oral dryness: muscarinic agonists
• Active extraglandular autoimmune disease: Glucocorticoids
• Immunomodulatory/Biologic: 2nd or 3rd line
#Sjogrens #Syndrome #Rheumatology #Diagnosis #Management
Behçet's Syndrome
Systemic disease associated with inflammation of multiple organs, small-vessel vasculitis and large-vessel vasculopathy
Epidemiology:
• Young adults 20 to 40 years of age
• Most common in Asia
• HLA-B51 association
• M > F
Clinical Manifestations:
• Oral Ulcerations: Recurrent oral aphthous ulcerations (painful)
• Urogenital Lesions (75% or more): Genital ulceration
• Ocular Disease (25-75%): Inflammatory eye disease (panuveitis, retinal vasculitis)
• Cutaneous Lesions (75%): acneiform lesions, erythema nodosum (septal panniculitis), superficial thrombophlebitis, pyoderma gangrenosum like lesions, pyoderma gangrenosum like lesions, erythema multiforme-like lesions, palpable purpura, Pathergy (an inflamed response to local skin injury)
• Neurologic Disease: Lesions in the corticospinal tract, brainstem, periventricular white matter, spinal cord, and basal ganglia, CNS (brainstem lesions, aseptic meningitis), MCC CNS symptoms (headache and diplopia)
• Vascular Disease: Arterial (MCC-small vessel vasculitis. Medium and large also involved), Venous disease (SVC/IVC occlusion, Budd-Chiari syndrome, dural sinus thrombosis, VTE)
• Cardiac Disease: Pericarditis, myocarditis, coronary arteritis +/- myocardial infarction, coronary artery aneurysms
Diagnosis:
No pathognomonic laboratory tests in Behcet syndrome (Clinical Dx). At least three episodes of recurrent oral ulcers in 12 months plus at least two more of the following:
• Genital ulcers
• Eye involvement (uveitis or retinal damage)
• Skin lesions
• Positive pathergy test (this is a skin prick test that can confirm Behcet disease)
Differential Diagnosis:
• Genital ulcerations
• Oral aphthae : SLE, Reactive arthritis,ervical adenopathy (PFAPA) syndrome, hyperimmunoglobulin D syndrome, and A20 haploinsufficiency (HA20)
• Gastrointestinal : Crohn disease, ulcerative colitis, spondyloarthritis
• Ocular: Giant retinal tears, Ischemia, Leukemia, Lymphoma Ocular melanoma
• Arthritis: SLE, Reactive Arthritis, AS
Treatment:
• Oral and genital ulcers-Topical glucocorticoids
• Recurrent mucocutaneous lesions-Colchicine
• Recurrent and chronic arthritis-Azathioprine, interferon alfa, or tumor necrosis factor CTNF)-a inhibitors
• Uveitis- Ophthalmology collaboration
• CNS exacerbations: high-dose glucocorticoids and azathioprine
• Severe or refractory disease : monoclonal TNF-aIpha inhibitor + oral DMARD
• Nonsurgical abdominal pain: Glucocorticoids 5-ASA or azathioprine
#Behcet #Syndrome #diagnosis #management #signs #symptoms #rheumatology #disease
Emergent Causes of Headache and Associated Risk Factors
Carbon monoxide poisoning
- Breathing in enclosed or confined spaces with engine exhaust or ventilation of heating equipment
- Multiple household members with the same symptoms
- Wintertime and working around machinery or equipment producing carbon monoxide (eg, furnaces)
Meningitis, encephalitis, abscess
- History of sinus or ear infection or recent surgical procedure
- Immunocompromised state
- General debilitation with decreased immunologic system function
- Acute febrile illness—any type
- Extremes of age
- Impacted living conditions (eg, military barracks, college dormitories)
- Lack of primary immunization
Temporal arteritis
- Age > 50
- Females more often than males (4:1)
- History of other collagen vascular diseases (eg, systemic lupus)
- Previous chronic meningitis
- Previous chronic illness, such as tuberculosis, parasitic or fungal infection
Glaucoma—acute angle closure
- Not associated with any usual or customary headache patterns
- History of previous glaucoma
- Age >30
- History of pain increasing in a dark environment
Increased intracranial pressure
- History of previous benign intracranial hypertension
- Presence of cerebrospinal fluid (CSF) shunt
- History of congenital brain or skull abnormalities
- Female gender
- Obesity
Cerebral venous sinus thrombosis
- Female gender
- Pregnancy, peripartum, hormone replacement therapy or oral contraceptive use
- Prothrombotic conditions
Reversible cerebral vasoconstriction syndrome
- Episodic sudden severe pain, with or without focal neurological findings or seizure
- Recurrent episodes over a period up to several weeks
- Exposure to adrenergic or serotonergic drugs
- Postpartum state
Subarachnoid hemorrhage (SAH)
- Sudden and severe pain; "worst headache of life"
- Acute severe pain after sexual intercourse or exertion
- History of SAH or cerebral aneurysm
- History of polycystic kidney disease
- Family history of SAH
- Hypertension—severe
- Previous vascular lesions in other areas of the body
- Young and middle-aged
Subdural hematoma
- History of alcohol dependency with or without trauma
- Current use of anticoagulation
Epidural hematoma
- Traumatic injury
- Lucid mentation followed by acute altered mentation or somnolence
- Anisocoria on physical examination
#headache #redflags #signs #symptoms #differential #emergency #diagnosis
Cryofibrinogenemia Summary
Cryofibrinogenemia Epidemiology:
• 40-70 years with a modest female predominance
Cryofibrinogenemia:
• The precipitation of a complex when plasma is cooled from the normal body temperature of 37°C to the near-freezing temperature of 4°C.
• This precipitating complex contains fibrinogen, fibrin, fibronectin, small amounts of fibrin split products, albumin, immunoglobulins and other plasma proteins which can plug blood vessels.
• Cryofibrinogen is distinguished from cryoglobulin (CG) since, it precipitates only in plasma and not in serum.
• Cryoglobulins precipitate in serum + plasma
Cryofibrinogen - Cryofibrinogen is a cold insoluble complex of:
• Fibrin
• Fibrinogen
• Fibrin split products with:
- Albumin
- Cold insoluble globulin
- Factor VIII
- Plasma proteins
Cryofibrinogenemia Symptoms:
• Asymptomatic or combination of:
- Hyperviscosity,
- Vascular reactivity (Skin necrosis)
- Thrombosis (Thrombotic vasculopathy)
• Paradoxical spontaneous bleeding may occur due to the depletion of clotting factors
Cryofibrinogenemia Can Be Divided Into Two Types:
1. Primary (essential)
2. Secondary form associated with autoimmune diseases, malignancies, vasculitis, sepsis or cryoglobulinemia
Associated Disorders:
• Malignancy
• Infections including coronavirus disease 2019 (COVID-19)
• Inflammatory processes:
• Systemic rheumatic diseases
• Thromboembolic conditions
Cryofibrinogenemia Clinical Manifestations - Findings may include:
• Cold sensitivity
• Painful ulcers
• Skin necrosis
• Purpura
• Livedo reticularis
• Painful or pruritic erythema (perniosis) of the extremities
• Arthralgias
• Raynaud phenomenon
• Simulates calciphylaxis clinicopathologically,
- Related conditions: Stroke, myocardial infarction, limb and bowel ischemia or infarction, thrombophlebitis, pulmonary emboli, and ocular thrombi including retinal arterial and/or venous occlusions, as well as gangrene
Cryofibrinogenemia Diagnosis:
• + Clinical findings/Presentation
• Asymptomatic: Plasma (CF) cryofibrinogen levels < than 50 mg/L
- Significant levels >1g/L
• Negative cryoglobulins
• Negative causes of secondary cryofibrinogenemia.
• Biopsy: Typical pathologic findings on biopsy of affected tissue
• Angio: Occlusion of small to medium-sized arteries
• Secondary CF: Presence of associated disease
Cryofibrinogenemia DDX:
• Calciphylaxis
• Cryoglobulinemia
• TTP, HUS and HIT
• Antiphospholipid syndrome
• Warfarin-induced skin necrosis
• DIC
• Septic emboli
• Frostbite
• Atherosclerotic PVD
• Atheroemboli
#Cryofibrinogenemia #diagnosis #rheumatology #hematology