Etiologies of Chronic Pancreatitis (progressive inflammatory changes in the pancreas that result in permanent structural damage and histologic fibrosis)

–Alcohol abuse (45 %) as well as cigarette use
-Recurrent acute pancreatitis
–Genetic (eg: CFTR, SPINK mutations)
-Chronic ductal obstruction
-Systemic diseases (eg: SLE, hyperparathyroidism, hypertriglyceridemia)
-Idiopathic
–AUTOIMMUNE–Can be Type 1 (part of IgG4 disease) vs. Type 2 (idiopathic duct-centric pancreatitis without systemic involvement or IgG4 +) 

Clinical manifestations of chronic pancreatitis

-Can be ASYMPTOMATIC
–Epigastric abdominal pain most common symptom however
–Pancreatic insufficiency (only after 90 % of pancreatic function lost) and manifests as steatorrhea and glucose intolerance/diabetes
-Remember that chronic pancreatitis puts you at increased risk for PANCREATIC CANCER

Lab/Imaging

-Amylase/Lipase usually NORMAL so not as helpful
–72 hour quantitative fecal fat (steatorrhea alone is non-specific!)
–Fecal elastase has high sensitivity and specificity for chronic pancreatitis
-KUB can show calcifications hinting towards chronic pancreatitis and MRCP/ultrasound can show pancreatic duct obstructions, dilations, strictures or fluid collections

Treatment

-Alcohol and smoking cessation!
-Creon supplementation, may also need fat-soluble (A,D,K,E) supplementation
-Analgesics for abdominal pain which is extremely hard to control. Minimize opioids but may be necessary for refractory pain.
-Specialized approaches include celiac nerve blocks, endoscopic surgery and surgical resection

IgG4 related disease

–Inflammatory and Fibrotic systemic condition where organs have tumefactive (swelling), IgG4 positive lymphoplasmacytic infiltrate with often elevated IgG4 serum levels but not always

Clinical manifestations of IgG4 related disease

–Pancreatic involvement (manifests as pancreatic mass which can mimic CANCER, recurrent pancreatitis, strictures etc.)
–Biliary involvement (biliary strictures leading to obstructive jaundice as well as sclerosing cholangitis)
-ANY organ can be affected (eg: thyroiditis, interstitial nephritis, salivary involvement) Diagnosis and Treatment

http://www.nature.com/nrrheum/journal/v10/n3/full/nrrheum.2013.183.html

Diagnosis
-Diagnosis is made with the HISORt criteria (need at least one criteria)-see below

–Treatment is with STEROIDS and may need immunomodulating therapy depending on clinical course.

Further reading

NEJM article on IgG4 related disease 

Syncope

-Defined as ABRUPT and TRANSIENT loss of conscious associated with loss of postural tone followed by complete and RAPID spontaneous recovery
-Before you start working up syncope, make sure it is not a mimic like a seizure!

How do you make the diagnosis?

-Keep in mind that the majority of syncopal episodes are of unknown etiology but the most common known etiology is neurocardiogenic or vasovagal syncope. Despite what you saw on that episode of Scrubs, this type of syncope is not diagnosed with a blood test
-A detailed H&P makes the diagnosis in about 50 % of patients with syncope, especially focusing on whether it was EXERTIONAL, Prodromal symptoms, changes in position during event, FAMILY HISTORY of sudden cardiac death, and any associated cardiac symptoms. 
–Check orthostatics and EKG on everyone (still low yield but minimal cost and EKG can help you look for more dangerous etiologies)
–Telemetry is reasonable and recommended if you suspect a cardiac etiology for the syncope based on the H&P and EKG

-Do NOT get brain imaging (CT/MRI) in simple syncope as the yield is extremely low unless high suspicion for intracranial mass 
-Echocardiogram and carotid ultrasound are also extremely low yield unless EKG or exam shows concerning features (eg: ejection murmur on exam concerning for AS, young male with severe LVH concerning for HOCM, bilateral carotid bruits)
-See below for common causes of syncope, diagnostic testing, and treatment (from Medscape)

What is the San Francisco Syncope Rule?

-One of the many prognostic rules to look at whether someone is at high risk for serious outcomes and may need to be admitted if they meet ANY of these criteria
-If they meet NONE of the criteria with no other obvious source of syncope (eg: melena on exam),  high NPV for serious outcomes from syncope at 7 or 30 days.

Conditions to look out for on an EKG of a young patient with Syncope

-HOCM
–Long QT syndrome (acquired or congenital) as increased risk of Torsades
-Brugada Syndrome
-Arrhythmogenic right ventricular dysplasia (ARVD)
-Arrhythmias
-Tachyarrhythmias (esp. VT but also WPW)
-Bradyarrhythmias (eg: heart block)

Workup of suspected LQTS

-Rule out secondary etiologies of prolonged Qtc (long list but includes many electrolyte abnormalities as well as DRUGS). BRADYCARDIA prolongs the QT interval.
-LQT1-LQT13 genetic testing as determining genotype can affect clinical course
-GXT testing to look for arrhythmias as well as monitor QT interval (normally decreases with increased HR but not always in LQTS)

Treatment

–Beta Blockers FIRST LINE but at higher risk for heart block
-Keep Mg and K at normal limits to avoid Qtc prolongation, avoid drugs that can worsen prolongation
-PPM, left cardiac sympathectomy, and AICD may be needed
-Referral to center with radiofrequency catheter ablation.

Glomerulonephritis (basic breakdown)

-Can be acute, chronic, or due to RPGN

1. Anti-GBM  disease 
2. Pauci-immune GN
   1. GPA
   2. EGPA
   3. MPA
3. Immune Complex GN
   1. Systemic involvement
      1. SLE
      2. Endocarditis
      3. Cryoglobulinemia
      4. HSP
   1. Isolated Renal
      1. IgA Nephropathy
      2. IRGA (Infection Related GN)
      3. MPGN

Clinical presentation of Glomerulonephritis

–Hematuria
–Dysmorphic RBC or RBC casts
-Sub-nephrotic range usually (but can be nephrotic range) proteinuria often with renal failure
-HTN
-Edema

How do you distinguish the etiology of an immune complex GN? 

                                      Check COMPLEMENT levels!

Diseases with LOW complement

1. SLE (low C3 and C4 and often + ANA Anti-dsDNA)
2. Cryoglobulinemia (Low C4 and C4, often associated with HCV with + Cryo)
3. Endocarditis (Low C3, RF for endocarditis, fever, + BC etc.)
4. IRGA (usually low C3, now always PSGN and Staph related GN is just as common now)-classic teaching is that PSGN occurs weeks after infection but can occur concurrently with infection with other etiologies such as Staph!)

Diseases with NORMAL complement

1. HSP (only systemic IC disease with normal complement)
2. IgA nephropathy (often compared to PSGN which has low complement and usually occurs weeks after infection later than with IgA nephropathy)

Lupus Nephritis

-Making the diagnosis of Lupus is commonly done using the SLICC criteria (see below).

-While not part of the criteria, SPLENOMEGALY can be seen with SLE like our patient and should make you suspect SLE!
-There are SIX classes of Lupus Nephritis and biopsy is important to guide therapy
-Nearly everyone with SLE requires a renal biopsy EXCEPT those with

1. Protein excretion <500 mg/day
2. Bland urine sediment (no dysmorphic RBC, RBC casts)
3. Normal creatinine

Classic Triad of Infectious Mono

-Fever
-Pharyngitis
-Lymphadenopathy

*Most common symptoms however are MALAISE and SORE THROAT. Less common but if you see Palatal Petechiae, think about Mono!

Epidemiology

-Most common in adolescents aged 10-19 but can be seen in adults as well

Etiology

-EBV (Epstein Barr Virus)-90-95 % people are EBV seropositive but long latency period.
-Spread by Saliva and sexual transmission (not just the kissing disease)

Diagnosis

-Heterophile antibodies (Monospot is using Horse RBC agglutination)
Sensitivity=85 % while Specificity=97-100 % (can be falsely negative up to 25 % in first week so VCA may be more helpful)
-VCA (Viral Capsid Antigen) IgG, IgM
-Peripheral smear may show >50 % lymphocytes with atypical lymphocytes (see below)

Signs and Symptoms 

–Presentation differs depends on whether young or old as those in older groups have more atypical presentations (see below) including neutropenia and severe infection like our patient had!

Differential Diagnosis

Always keep Acute HIV infection in mind if you are thinking Mono but also includes Strep pharyngitis, Acute CMV, Toxoplasmosis, and Viral Pharyngitis.

Treatment

-Supportive care, hydration, NSAIDs/APAP use PRN
-No benefit to support routine use of H2 blockers, Acyclovir, or steroids although Acyclovir can decrease shedding time of virus
-4 weeks no contact sports (due to very low risk of splenic rupture) but they do NOT need to be on bed rest.
-Avoid ampicillin/amoxicillin as can classically cause a morbilliform rash

Further reading

NEJM article on Infectious Mononucleosis 

Definition: a foreign body resulting from accumulation of ingested material – most commonly found as a hard mass / concentration in the stomach.

Types

Phytobezoar: composed of vegetable matter – MOST COMMON

Trichobezoar: composed of hair

Pharmacobezoar: composed of ingested medications

Other: composed of a variety of other substances (tissue paper, shallac, fungus, styrofoam, cement, etc.)

Pathogenesis

• Ingestion of indigestible material
• Delayed gastric emptying
• Composition / Interaction with gastric material – unripe persimmon fruit contain shibuol (soluble tamin), which forms coagulate when mixed with gastric material

Rapunzel Syndrome: trichobezoar from the stomach to the terminal ileum

Epidemiology: RARE

• Incidence ~0.3% on EGD
• Phytobezoars – male ~40-50 years old
• Trichobezoars – female ~20s; associated with underlying psychiatric disorder

Risk Factors:

• Gastric dysmotility – underlying anatomic abnormality may predispose to formation
  • 70-94% have had gastric surgery
  • 54-80% have undergone vagotomy / pyloroplasty
• Gastroparesis
• Gastric outlet obstruction
• Dehydration
• Medications – insoluble carrying vehicle, high hygroscopy

Clinical Manifestations:

• Abdominal pain
• Nausea/vomiting
• Early satiety
• Anorexia
• Weight loss
• GIB/Obstruction – NOT COMMON

Physical exam: unremarkable in most, occasional abdominal pain and halitosis.  Alopecia in trichobezoars.

Imaging:

• Abdominal radiograph with/without barium
• Abdominal US
• CT scan

Complications:

• GI perforation
• Peritonitis
• Protein-losing enteropathy
• Steatorrhea
• Pancreatitits
• Intussusception

Diagnosis:

• EGD is required to establish the diagnosis of a gastric bezoar AND to obtain samples to determine composition/type

Management: controversial in the absence of studies comparing different modalities

• Chemical dissolution – administration of an agent to degrade the gastric bezoar (non-invasive / inexpensive); potential complication of SO from partially dissolved bezoars ~ 6 weeks later
  • Coca-cola – 3L/12H; low pH, mucolytic effect, ↑ sodium bicarb content, CO2 bubbles (widely available, inexpensive, well-tolerated)
  • Cellulase – dissolves cellulose found in plant fiber / phytobezoars
  • Papain – type of meat tenderizer with many complications
  • Acetylcysteine – low success rates (~50%)
• Endoscopic removal – fragmenting the bezoar with water jet, direct suction (large channel), forceps, snares; allow the fragments to be cleared.
• Adjuvant prokinetics – Metoclopramide typically used in conjunction with endoscopic / chemical therapy because it may decrease the time to dissolution.
• Surgery – reserved for patients that fail chemical AND endoscopic treatment OR those with complications (obstruction/bleeding) OR when composition is not amendable to either other treatment options.

Wheezes: “All that wheezes is not asthma, but all that wheezes is obstruction.”

Extrathoracic Upper Airway

Nasopharynx & Oropharynx

• Tonsillar Hypertrophy
• Pharyngitis
• Peritonsillar abscess
• Retropharyngeal abscess

Larynogpharynx & Larynx

• Epiglottis
• Paradoxical Vocal Cord Movement
• Vocal Cord Paralysis
• Anaphylaxis & Laryngeal Edema
• Post Nasal Drip
• Benign/Malignant Tumors
• Relapsing Polychondritis (subglottic stenosis)

Intrathoracic Upper/Lower Airways

Trachea

• Tracheal stenosis
• Tracheomalacia
• Goiter

Proximal Airways

• Foreign-body aspiration
• Bronchitis

Distal Airways

• Asthma
• COPD
• Pulmonary edema
• Bronchiectasis

“Thumb sign” of epiglottitis

Infectious causes of epiglottitits

Bacterial:

• H. influenza (type B)
• Steptococcus pneumoniae
• Staphylococcus aureus (MRSA/MSSA)
• B-hemolytic streptoccoci (A-G)

Viral:

• HSV
• VZV
• EBV
• Para/Influenza

Non-Infectious

• Thermal injury
• Foreign body

Risk Factors:

Children: incomplete/lack of immunizations; immune deficiency

Adults: comorbid condition (HTN, DM, PSA, etc.), immune deficiency

3 D’s of Epiglottitis – Drooling, Dysphagia, Distress

Presentation:

Children: respiratory distress, anxiety, posture (see below), stridor, muffled (hot potato) voice.

Tripod Posture / Sniffling Position:

Adults: sore throat/odynophagia (~90%), fever, muffled voice, drooling, stridor/respiratory distress, hoarseness

Onset:

Children: <24 hours (frequently <12 hours)

Adults: 48 hours (65%)

Treatment:

First – secure airway!

Next – empiric antibiotics (typically 3rd generation cephalosporin and MRSA coverage)

Myasthenia Gravis: autoimmune – directed against post-synaptic NM junction; look for bulbar muscle involvement that gets worse with activity.

Sign/Symptoms:

1. Ocular: ptosis/diplopia, EOM involvement, no pupillary involvement
2. Bulbar: dysarthria, dysphagia, fatigue with chewing
3. Weakness: proximal limb weakness, facial/neck weakness
4. Respiratory muscle weakness ⇒ Myasthenia crisis

Tests:

Bedside

• Ice-pack test – improved ptosis with ice pack administration
• Tensilon (edraphnium) – acetylchoinesterase inhibitor with rapid onset/short duration; NOT SPECIFIC

Serologic

• Acetylecholine receptor antibody
• Muscle specific tyrosine kinase antibody (Anti-MUSK)

Electrophysiologic

• Repetitive nerve stimulation: ↓ amplitude with repetitive stimulation ~75% have thymic abnormalities (85% thymic hyperplasia, 15% thymoma)

GBS: ascending motor and sensory involvement, symmetric

Timing: <4 weeks

Pathophysiology: Due to molecular mimicry → immune response to preceding infection cross reacts to peripheral nerve

Common trigger: Campylobacter Jejuni (most common), CMV, EBV, HIV, VZV, mycoplasma, Zika

Physical Exam:

• Absent/depressed DTRs (90%)
• Ascending weakness (~90%)
• Paresthesias (80%)
• Facial weakness/bulbar signs (55%)

LP: Albumino-cytologic dissociation

Miller Fisher Variant

• Ophthalmoplegia
• Ataxia
• Areflexia

Botulism: bulbar involvement – spread in craniocaudal direction ~ “descending paralysis” with CN/eye involvement

Most common etiologies for BLOODY pleural effision:

• Trauma
• Malignancy
• Pulmonary infarct
• Post-cardiac injury

Lights Criteria: one criteria = EXUDATIVE effusion

1. Pleural total protein / serum total protein > 0.5
2. Pleural LDH / serum LDH > 0.6
3. Pleural LDH ≥ 2/3 ULN for serum LDH

* Lights criteria is SENSITIVE, but NOT SPECIFIC – you do not want to miss an exudative effusion, so you want to a low false negative rate.

* For patients with a high suspicion for transudative effusion, but meets Lights criteria (i.e. CHF following initiation of diuresis), check serum albumin and pleural albumin (if serum – pleural < 1.2 mg/dL, confirms diagnosis of exudative effusion).

Transudative Effusions (not a complete list):

• CHF (~90%)
• Cirrhosis (hepatic hydrothorax)
• Severe hypoalbuminemia
• Nephrotic syndrome
• Peritoneal dialysis
• Myexedma
• Constrictive pericarditits
• SVC syndrome

Exudative Effusion (not a complete list):

• Infection (PNA/TB)
• Malignancy
• CTD
• Pancreatitis
• Trauma
• PE/Pulmonary infarct
• Post heart surgery
• Esophageal rupture

If exudative effusion, start with cell count/diff

• PMNs > 50% – parapneumonic, PE, pancreatitis
• Lymphs > 50% – Cancer, TB, fungal, post-surgery
• Eosinophils >10% – Hemothorax, drug reaction, parasite infection

Myopathy is not only due to trauma, crush injury or statins! 

Etiologies of non-traumatic-non-exertional rhabdomyolysis (elevated CK)

–ALCOHOL, illicit drugs- from A (methAmphetamine) to Z (ecstasy), all are associated with rhabdo
–Medical drugs, commonly statins/fibrates but MANY implicated drugs (see below
-Infectious (including HIV!)
-Seizures, DTs, or restraints (avoid prolonged restraints of this reason and re-assess need for them frequently
–Hypothyroidism (more on this later)-Check that TSH!
-NMS, Malignant Hyperthermia
–Inflammatory myopathies(Dermatomyositis/Polymyositis/Dermatomyositis)
–Electrolyte abnormalities (eg: HypoK, HypoPhos)

List of implicated drugs (not a comprehensive list)

Make sure you do a comprehensive history when evaluating for rhabdo and consider secondary causes per above, including meds and thyroid abnormalities

What are some manifestations of SEVERE hypothyroidism (Myxedema Coma)

-See our other blog post for more details but the THREE cardinal features of Myxedema Coma are ALTERED MENTAL STATUS (not commonly Coma as the name states), HYPOthermia, and a PRECIPITATING EVENT (commonly an infection, or cold exposure, or MI or trauma)
-The “classic” patient who gets Myxedema Coma is an elderly female >60 years with history of untreated hypothyroidism presenting during the winter months. However, classic is not always so classic.
-Other findings include Bradycardia, HYPOnatremia, HYPOglycemia, and HYPOtension

Treatment of Myxedema Coma

–IV Levothyroxine (L4, sometimes L3 but controversial) along with stress dose steroids unless adrenal insufficiency is ruled out (get that AM cortisol!). Otherwise you can precipitate an ADRENAL CRISIS

What does hypothyroid myopathy look like? 

-Elevation in CK usually less than 10x ULN (seen in 60-90 % of patients), usually triggered by intense exercise or concurrent statin therapy (like our patient)
–Muscle hypertrophy (thickened doughy appearance of skin and subQ tissues)
–Proximal myopathy (progressive symmetric proximal weakness- can look like an inflammatory myopathy!)

Treatment

-Treat the hypothyroidism and symptoms usually improve

Take home point

-Did I mention that hypothyroidism is a common etiology of rhabdomyolysis?

What is a monoclonal gammopathy?

-Proliferation of single clone of plasma cells (M protein)
-Remember M is for monoclonal, not for IgM
-Can be detected in serum and/or urine
-M protein consists of heavy chain complexed with kappa/lambda light chain or free kappa/lambda light chain. See our patient’s spike below!

What can cause a monoclonal gammopathy?

-Although we commonly think about malignant processes, there are BENIGN etiologies including CTD, vasculitis, viral infections, or even post-transplant. See below for example from BCMJ

Credit: http://www.bcmj.org/articles/monoclonal-gammopathy-and-primary-care

What tests should you order next if you suspect a monoclonal gammopathy?

-Start with LFTS and look at your TOTAL PROTEIN and ALBUMIN level. If you see a high TP and a low albumin (high protein gap), you should worry that there is a monoclonal gammopathy
–SPEP and UPEP and allow measurement of the concentration of the M protein but does NOT tell you the isotype. For that you need to do the next step
-Confirm with IMMUNOFIXATION and check free light chain assay (FLC)
-Serum Immunoglobulins can tell if you high or low but do not establish the clonality 

What are the diagnostic criteria for Waldenstrom’s Macroglobulinemia?

–IgM (remember to flip that W to remember that Waldenstroms has an IgM spike) monoclonal gammopathy of any size
–Greater than 10 % of Bone Marrow Biopsy show lymphoplasmacytic features
-Typical immunophenotype (B cell markers eg: CD20)

Clinical Manifestations

-Can be ASYMPTOMATIC! known as Smoldering Waldenstroms
-Due to IgM deposition, can see peripheral neuropathy and hyperviscosity syndrome.

–Hyperviscosity Syndrome is a LIFE-THREATENING EMERGENCY that is treated with Plasma Exchange and symptoms can be non-specific (blurry vision, epistaxis, headache, vertigo but can cause stroke, coma or even CHF)
-Diagnosis of Hyperviscosity syndrome is CLINICAL but unlikely unless Serum Viscosity >4 CP (Centipoises) and IgM spike>4. Remember that Plasma Exchange does NOT treat the underlying cause!

-Due to infiltration, can see anemia, hepatosplenomegaly, and lymphadenopathy
-Bleeding manifestations, most commonly EPISTAXIS, but can be non-specific like fatigue, weakness, and weight loss

What are two associations with Waldenstrom’s to keep in mind?

-Associated with Type I Cryoglobulinemia (SMV with palpable purpura)
–Cold agglutinin hemolytic anemia (AIHA with +DAT)

Treatment of Waldenstroms

-If asymptomatic, does NOT need to be treated but risk of developing symptoms
-If hyperviscosity syndrome==>Plasma Exchange
–Medical therapy includes TKI (eg: Ibrutinib), alkylating agents (eg: Bendamustine), purine analogs (eg: Cladribine), steroids and HSCT if candidate.
-AVOID PRBC transfusions if possible as can worsen hyperviscosity.