GBS Variants:

-AIDP (Acute inflammatory demyelinating polyneuropathy)- 85-95 % of GBS
-Miller Fisher Variant (5 % US but up to 25 % in Japan)
-AMAN (Acute motor axonal neuropathy)
-AMSAN (Acute sensorimotor axonal neuropathy)

Timing:

Acute (<4 weeks)

Pathophysiology:

Due to molecular mimicry from immune response to preceding infection that cross reacts with components of the peripheral nerve.

Diagnostic Criteria:

1. Progressive weakness of ≥ 2 limbs due to neuropathy
2. Areflexia
3. Disease course < 4 weeks
4. Exclusion of other causes

Supportive criteria:

1. Symmetric weakness
2. Mild sensory involvement
3. Absence of fever
4. Typical CSF profile
5. EMG evidence of demylination

Most common infectious triggers:
-Campylobacter Jejuni (most common), CMV, EBV, HIV, VZV, Mycoplasma, and even Zika virus

Most sensitive physical exam findings in GBS

-Absent/Depressed DTR (90 %)
-Ascending extremity weakness (90 %)
-Paresthesias (80 %)
-Dysautonomia (70 %)
-Facial weakness or bulbar signs (55 %)
-Back/extremity pain, respiratory failure, oculomotor weakness

What do you see on LP?

Albumino-cytologic dissociation (normal WBC with high protein)

Miller Fisher variant TRIAD:

-Ophthalmoplegia
-Ataxia
-Areflexia
Antibodies against GQ1b (anti-ganglioside) present in 85-90 % of patients

Treatment

-Supportive treatment
-IVIG
-Plasma Exchange

Remember that steroids are not effective!

Surreptitious Insulin Use:
– Exogenous insulin intake is associated with increased insulin and low C-peptide levels

Whipple’s Triad:
1.Symptoms consistent with hypoglycemia
2.Documented low plasma glucose when symptoms are present
3.Relief of symptoms following resolution of hypoglycemia

– Consider a psychiatric evaluation in patient’s suspected of intentional exogenous insulin use

– Endogenous insulin is formed as two insulin chains (A&B) linked by C-peptide.  Measurement of C-peptide can help distinguish from endogenous versus exogenous insulin

Insulinoma:
Diagnosis:
– Clinical + measurement of insulin (normal or elevated), proinsulin (normal or elevated), and C-peptide (normal or elevated)
– Localization of tumor with imaging; start with CT of the abdomen

– Use a urine sulfonylurea toxicity screen to distinguish insulinoma from sulfonylurea ingestion

Pheochromocytoma:

– always think about pheo when the clinical case includes episodes of hypertension and headache

– Pheochromocytomas are tumors composed of chromaffin cells of the adrenal gland

– Pheochromocytomas almost always realease catecholamines

Classic Triad:

– Diaphoresis

– Headache

– Tachycardia

Genetic disorder associated with pheochromocytoma:

– MEN 2A and 2B

– Neurofibromatosis type 1

– Von Hippel-Lindau syndrome

Diagnosis: – Plasma / Urine catecholamines

– plasma high sensitivity (96-100%), but lower specificity (85-89%); 24 hour urine sensitivity/specificity (91-98%)

– Plasma will exclude a pheo when negative, but need to confirm if positive

– Following biochemical diagnosis – radiographic localization is needed

Preoperative management:

– Alpha-blocker – typically with phenoxybenzamine – is first-line therapy; followed by B-blockers (metoprolol, propranolol) to treat reflex tachycardia

MEN 1, 2A, and 2B disorders:

MEN 1: Pituitary adenoma, Parathyroid hyperplasia, Pancreatic tumors

MEN 2A: Medullary thyroid cancer, Parathyroid hyperplasia, Pheochromcytoma

MEN 2B: Medullary thyroid cancer, Marfanoid habitus/Mucosal neuroma, Pheochromocytoma

Cushing Syndrome:
– Bright purple abdominal striae always, always, always are associated with Cushing syndrome – striae larger than 1 cm in width are highly specific for hypercortisolism

Other classic stigmata:
– cervicodorsal fat pad aka “buffalo hump,” acne, hirsutism, moon facies, plethora, easy bruising, hypertension, insulin resistance, hypokalemic metabolic alkalosis, osteoporosis

Cause:
– Elevated cortisol
– Most common cause is exogenous glucocorticoid therapy for another cause

3 biochemical testing options for CS:
– 1 mg (low dose) dexamethasone suppression test – failure to suppress AM cortisol indicates true Cushing syndrome
– 24 hour urine free cortisol (UFC) – excludes CS when not elevated
– Late-night salivary cortisol
Never measure a random cortisol as part of the work up

After confirming CS biochemically, measure ACTH to establish etiology
– differentiate between ACTH-dependent/Cushing Disease (usually > 20 pg/mL) and ACTH-independent (usually < 5 pg/mL)

If ACTH-dependent CS: order pituitary MRI
If ACTH-independent CS: adrenal gland imaging (either CT or MRI)

ACTH-secreting pituitary adenoma is known as Cushing disease
Pearl: pituitary adenomas do not suppress with low-dose dex, but do suppress with high dose

Other possible ACTH-secreting tumors (but very rare):
– An ectopic ACTH-secreting tumor
– Usually these are primary lung cancers or a carcinoid tumor
– The clinical presentation of an ectopic lung tumor usually is less cushingoid (presenting with only HTN and metabolic abnormalities) due to the rapid growth of these tumors

Pneumocystis jiroveci pneumonia (PJP):
– opportunistic infections are the most common etiologies of infection in patients 1-6 months after solid organ transplant.
Common signs/symptoms of PJP:
– Progressive exertional dyspnea (95%)
– Fever (90%)
– Non-productive cough (90%)
Pearl: walk patients with suspected PCP to reveal hypoxemia!

Diagnosis:
– Direct fluorescent antibody stain (DFA stain)
– Gomori methenamine silver stain (GMS stain)
*Must visualize the cystic/trophic forms directly

Treatment: TMP/SMX for 21 days
– Add steroids for pO2 ≤ 70 or A-a gradient ≥ 35

Toxic Shock Syndrome:
– expect a TSS board question to present as overwhelming sepsis in the context of a menstruating female or a post-surgical wound infection
– toxins (called super antigens) stimulate cytokine production, resulting in systemic signs of shock

Triad of TSS:
– Shock
– Fever
– Rash – diffuse macular rash with subsequent desquamation, especially on the palms and soles
*Along with involvement of at least 3 organ systems

Organisms often involved:
– S. aureus
– S. pyogenes

Treatment:
S. pyogenes: penicillin plus clindamycin
MSSA: Nafcillin or oxcillin plus clindamycin
MRSA: Vancomycin plus clindamycin
* add clindamycin to suppress protein synthesis and, therefore, toxin production

Scarlet Fever:
Key features:
– “circumoral pallor” – pale area around mouth
– “Pastia lines” – petechial lines in the skin creases
– desquemation

Most common organism: Group A Streptococcus

5 “S'” of Scarlet Fever:
– Streptococci (causative organism)
– Sorethorat
– Swollen tonsils
– Strawberry tongue
– Sandpaper rash

Treatment: Oral penicillin V; amoxicillin, 1st generation cephalosporins, and IM PCN G are alternatives

Lyme Disease:
– Erythema migrans is the associated rash

– Borelia burgdorferi is the causitive organism and Ixodes tick is the vector
– > 95% of cases occur in regions where the Ixodes tick is abundant

Other infections spread by Ixodes tick:
– Babesiosis
– Anaplasmosis

Signs/Symptoms of different stages of Lyme disease:
Localized: erythema migrans (target lesion at site of tick attachment ~ 60-80%), fever/other systemic symptoms are rarely present
Early disseminated: erythema migrans at multiple sites, febrile illness with constitutional symptoms (myalgia, arthralgia, and headache)
Cardiac: asymptomatic PR prolongation → complete heart block
Neurologic: facial nerve palsy (most common) either unilateral or bilateral
Late disseminated: oligoarticular inflammatory arthritis involving large joints (i.e. knee)

Rocky Mountain Spotted Fever:
Look for a history of exposure to ticks in endemic areas (southeast / south central US) and features of:
– Pancytopenia (esp thrombocytopenia)
– Hyponatremia
– No evidence of DIC (normal PT/PTT)
– ↑ transaminases

Rash of RMSF:
– >85% of patients by 1 week
– May lag behind other symptoms (~50% by day 3)
– Typically starts at the distal extremities and progress centrally; involves the palms/soles in >30% and typicially spares the face

Treatment:
– Doxycycline; choloramphenicol is an alternative option in pregnancy

Ehrlichiosis:
Think of Ehrlichia as “Rocky Moutain spotless fever”
– presents similarly to Anaplasmosis
– endemic to the southcentral and southeastern US
– spread via the Lone Star tick

Symptoms in order of frequency:
Fever (~90%) > headache > myalgia > arthralgia > meningismus

– Blood smear can help with visualization of intracytoplasmic inclusions in WBCs; only present in ~30%

Treatment:
– Doxycycline

Coccidioides Infection (Valley Fever):
– Clues to be aware of: Arizona/New Mexico and erythema nodosum
– Endemic to SW US (Arizona, New Mexico, Texas, and central valley of California)
– Route of infection: inhalation of fungal particles found in the sand
– Arthralgia of multiple joints “desert rheumatism” is common.

Diagnosis confirmed on fungal stains
– Thick walled spherules (10-80 uM) with endospores are seen in tissue

No treatment for mild disease; use itraconazole or fluconazole for severe illness

Histoplasmosis:
Exposure history is key here; think of histo with any of the following exposures in the SE/SC US:
– Bats (or guano)
– “Spelunking” (cave exposure)
– Farm buildings / bird-roosting locations

Most infections are subclinical (~95%); can see mucocutaneous lesions
Antigen detection in urine great for disseminated infections (>85%)

Blastomycosis:
– Endemic to Ohio and Mississippi/ River valleys

– Primarily a pulmonary infection, may disseminate to the skin and bone
– Well demarcated skin lesion is most common manifestation of disseminated disease

– Appears as a broad based budding pattern at 37 C

Normal Pressure Hydrocephalus:
Crude mnemonic: Wet (incontinence), Wobbly (ataxia), and Wacky (dementia)
Abnormal gait typically develops first!
“Magnetic gait” – is the characteristic gait of NPH – the patient’s walk appears as if his/her feet are stuck to the floor.
The gait is wide based, with slow, small steps, and reduced foot-to-floor clearance

Visualize hydrocephalus on CT/MRI – specifically ventriculomegaly that is disproportionate to corticol atrophy

LP: Normal (or slighty elevated) opening pressure and cell count

Standard of care: Ventriculoperitoneal (VP) shut – can perform large volume (30-50 mL) LP prior to placement to verify benefit

Cluster Headache:
Presentation: Shorter duration (usually < 3 hours), ipsilateral congestion and lacrimation with headache, nocturnal attacks
Epidemiology: Young or middle aged, male sex, history of cigarette smoking
Common trigger: Alcohol

First-line therapy: Inhalation of 100% oxygen and/or SQ or intranasal sumatriptans
Prevention medication: Verapamil

Transverse Myelitis:
TM is thought to be due to an autoimmune inflammation
~50% of the time it is preceded by an infection

Diagnosis requires:
– Presence of clinical features
– Evidence of inflammation (either leukocytosis in CSF or contrast enhancement on MRI)
– Exclusion of other potential causes

Treatment: IV methylprednisolone; plasmapheresis or cyclophosphamide for refractory disease

Alzheimer Disease:
Presentation: >60 years old, decline is insidious and progressive, definite impairment in 2 or more domains of cognition that impacts daily living

Treatment options:
– Cholinesterase inhibitors: Donepezil, Rivastigmine, Galantamine
– N-methyl-D-asapartate receptor antagonists: Memantine
*mild improvements in measured cognition and performance of some activities; no clinically significant outcome

Frontotemproal Dementia:
– 3rd most common type of neurodegenerative disorder (2nd in those < 65 years old); average age of onset is 50-60
– Social behavior / personality changes are variable
– Genetics of FTD are heterogenous ~40% of patients with FTD have at least one family member with a neurodegenerative disorder

Difference with Lewy Body Dementia – Lack of significant psychosis – especially visual hallucinations

Parkinson Disease:
4 main features:
– Tremor: “pill-rolling” and always gets better with action
– Bradykinesia
– Rigidity
– Gait/Postural impairment: “festinating gait” – meaning hurried small shuffles, often on tippy toes
* diagnostic criteria require the presence of bradykinesia with at least one other cardinal feature
* MRI is recommended to rule out vascular lesions and hydrocephalus when suspected

Treatment options:
– Non-pharmacologic: rigorous daily exercise
– Pharmacologic: Dopamine substrate (levodopa), Decarboxylase inhibitors (carbidopa), Dopamine agonists (Ropinirole, Bromocriptine, Pergolide), Catechol-O-methyltransferase inhibitors (Entacapone, Tolcapone), Monoamine oxidase type B inhibitors (Selegiline, Rasagiline), Glutamate antagonist (Amatadine), Anticholinergic agents (Benztropine)
– Surgical: Deep brain stimulation (DBS) – consider in patients who have sustained motor benefit from medication, but are limited by adverse effect of medications

Myasthenia Gravis:
Cause: autoimmune disease directed against post-synaptic NM junction
Labs:
– Anti-acetylchoine receptor antibodies (~90% sensitive)
– Anti-muscle-specific kinase (MuSK) antibodies
EMG: repetitive nerve stimulation shows decremental response
Imaging: CT or MRI of mediastinum to screen for thymoma (~15% present, 85% hyperplasia)

Treatment:
– Cholinesterase inhibitors: pyridostigmine
– Glucocorticoids
– Immunosuppressive agents: azathioprine, cyclosporine, etc.

Crisis Treatment:
– Plasmapheresis or IVIG

Lambert-Eaton Syndrome:
Cause: autoantibodies against voltage-gated calcium channels located at the presynaptic NM junction
Associations: small cell lung cancer – can occur before tumor has been discovered; found in as many as 60% of patients

Differentiate from MG:
– Repetitive contraction IMPROVES muscle strength
– Hyporeflexia and dysautonomia are also present

Treatment:
– Remove the malignancy
– IVIG +/- immunomodulators

Melioidosis (Whitmore’s disease)

-Caused by the Gram (-) organism Burkholderia pseudomallei

Epidemiology

–Predominantly in Southeast Asia, Northern Australia, and China (most commonly from Thailand, Malaysia, Singapore)

Transmission

–Percutaneous inoculation (soil/contaminated water)
-Inhalation (more common during severe weather events, eg:Tsunami/Hurricane)
-Aspiration
-Rarely Ingestion

Risk factors

–Occupational exposure (Eg: Rice farming)
–Immunocompromised
–DMII
–Alcohol use
–CKD
–Chronic lung disease
–Thalassemia

However, can occur in healthy individuals as well! 

Clinical Manifestations

1)Localized Infection-skin ulcers/abscesses
2)Pulmonary Infection->50 % of patients, with >25 % having cavitary pulmonary nodules 
3)Bloodstream infection-More than half of patients have bacteremia on presentation and septic shock develops in >20 % of patients 
4)Disseminated infection-Septic Arthritis, osteomyelitis, but can form parenchymal abscesses in ANY organ (eg: Spleen, Kidney, Prostate, Brain amongst others)

Can MIMIC Tb and Malignancy-Consider Melioidosis in any patient with cavitary nodules and skin findings! 

Treatment 

Remember that Burkholderia is inherently RESISTANT to penicillin, ampicillin, 1st/2nd gen cephalosporins amongst others-Treatment is very prolonged!

Intensive phase (10-14d): IV Ceftazidime, Meropenem, or Imipenem
Oral Eradication Therapy (3-6 months): TMP-SMX (preferred over doxycycline)

Source Control! Search and Treat internal-organ abscesses 

Steps to an Acid/Base Problem:

1. Step 1: Check for internal consistency[H+] = 24 x pC02/HCO3
2. Step 2: Use pH to determine primary disorder
3. Step 3: Calculate the AGAG = [Na+] – [Cl- + HCO3]
4. Step 4: Determine the presence of additional disordersCorrected HCO3 = measured HCO3 + [AG – 12]
5. Step 5: Calculate the expected pC02 for metabolic acidosis (Winter’s Formula)Expected PC02 = 1.5 (HCO3) +8 +/- 2

5 Etiologies with AST/ALT elevations > 1000:

• Drugs/Toxins (acetaminophen, toxic mushrooms, etc.)
• Hepatic ischemia
• Acute viral hepatitis
• Acute autoimmune hepatitis
• Wilson disease

3 components that define acute liver injury:

• Elevated aminotransferases
• Hepatic encephalopathy
• Elevated PT/INR

*No preexisting cirrhosis or liver disease; <26 weeks

Acetaminophen Toxicity:

• 4 grams is the daily maximum recommended dose
• N-acetylcysteine is the treatment of choice in suspected acetaminophen toxicity -nmay be given IV, using a 20 hour protocol, or orally, using a 72 hour protocol
• Use the Rumack-Matthew nomogram to elevate for poisoning severity

Options for renal replacement therapy (RRT):

• Hemodialysis
• Peritoneal dialysis
• Transplantation
• Non-dialytic management – manage symptoms and focus on QOL

Peritoneal dialysis – a dialysate solution is intermittently instilled into the peritoneal cavity via an indwelling catheter, and excess water/solutes are removed by osmosis and diffusion across the peritoneal membrane into the dialysis solution.

Two different options for PD exist:

1. Continuous ambulatory peritoneal dialysis (CAPD)
2. Automated peritoneal dialysis (APD)

   *CAPD does not require a machine, while APD relies on a “cycler” to fill and empty your belly 3-5 times during the night

   *There is no difference in clinical outcome between PD and HD – although there is a trend toward superior outcomes for PD patients with new-onset ESRD who have residual kidney function

Potential complications with PD:

• Peritonitis – from frequent access via the catheter or from perforation or microperforation of bowel
• Hernias at catheter site
• Subcutaneous edema
• Difficulty draining catheter (often due to constipation)
• Pleural effusions
• Sclerosing peritonitis: scarring/fibrosis from recurrent peritonitis – can lead to bowel constriction.  Prognosis is extremely poor (often fatal) and treatment requires surgical stripping.

Diagnosis of peritonitis requires 2 out of 3 of the following:

• Clinical signs of peritonitis
• Peritoneal fluid WBC > 100 cells/mm3 with >50% PMNs
• Positive peritoneal fluid culture

Common clinical manifestations of PD related peritonitis:

• Abdominal pain (79-88%)
• Cloudy peritoneal effluent (84%)
• Fever (>37.5 C) (29-53%)
• Nausea/Vomiting (31-51%)
• Hypotension (~18%)

Most common organisms of peritonitis in PD patients:

• Gram-positive organisms ~ 50% -Coagulase-negative staph (S. epidermidis) and S. aureus
• Gram-negative organisms ~ 15%
• Fungal ~2%
• Polymicrobial ~ 4%
• Culture negative ~ 20%

Empiric Antibiotic Regimen:

• Gram positive coverage – typically Vancomycin (or 1st generation cephalosporin)
• Gram negative coverage – typically 3rd generation cephalosporin
• Fungal prophylaxis while on ABX – typically nystatin

Indications for PD catheter removal:

• Relapsing peritonitis – episode of peritonitis with the same organism that caused the preceding episode within 4 weeks of completing antibiotics
• Refractory peritonitis – peritonitis that does not respond to appropriate antibiotics within 5 days
• Refractory catheter infection – exit-site/tunnel infections
• Fungal or mycobacterial peritonitis

Adrenal Anatomy:

Primary Adrenal Failure (Addison’s Disease):

• Failure of the adrenal cortex
• Prevalence 10-15/100,000 persons
• Etiology – Autoimmune adenitis ~70-80%; 2/3 will have at least one other autoimmune endocrine disorder; TB infiltration ~ 7-20%

Diagnostic Algorithm:

Adrenocorticotropic Hormone Deficiency (secondary cortisol deficiency):

Etiology:

1. Exogenous glucocorticoid use
2. Damage to the pituitary gland/stock

• Reminder of intact adrenal cortex will be a normal renin/aldosterone ratio
• Less risk for hypotension, hyponatremi, adrenal crisis than primary failure
• No hyperpigementation due to lack of hypersecrtion of ACTH

Multiple case reports of megase induced secondary adrenal insufficency

Fever of Unknown Origin Criteria:

• Fever > 38.3 on several occasions
• Duration of fever > 3 weeks
• Uncertain diagnosis after 1 week of inpatient investigation

5 Main Etiologies for FUO:

• Infection
• Malignancy
• Connective tissue disease
• Other
• No diagnosis

Adult Onset Still’s Disease (AOSD):

• Very uncommon – estimated annual incidence of 0.16 cases per 100,000 people
• Equal distribution between the sexes
• Bimodal age distribution: one peak between 15-25 and the other between 36-46 years old
• Diagnosis of exclusion, must exclude infection, malignancy, or other rheumatologic disease.

AOSD is multisystem inflammatory disease characterized by 4 major findings:

1. High spiking fevers
2. Salmon-color rash
3. Arthritis
4. High neutrophil counts

AOSD Laboratory Findings:

• Elevated ESR / CRP (99%)
• Elevated Ferritin (~75%)
• Leukocytosis > 10,000/mm3 (92%), >15,000/mm3 (81%) with neutrophil predominance (>80%)
• Abnormal LFTs (~ 75%)
• Negative ANA (92%)
• Negative RF (93%)

Yamaguchi Criteria for AOSD:

• Diagnosis requires 5 criteria total – with at least 2 major criteria

AOSD Treatment:

Initial therapeutic decisions should be based on the degree of disease activity:

• Mild disease: fevers, rash, and/or mild arthritis
• Moderate disease: high fevers, debilitating joint symptoms, evidence of internal organ involvement that is not life-threating or severe
• Severe disease: presence of life-threating organ involvement

Treatment options:

• NSAIDS – effective alone for 20% of mild patients
• Glucocorticoids – should be started in all patients meeting moderate disease criteria
• Methotrexate – used in patient’s who fail to improve with steroids
• Can also consider other DMARDs – will not be discussed here!

Which Asymptomatic patients should you screen for syphilis?

–HIV
–MSM
–Partner with syphilis
–High risk sexual behavior/history of incarceration or commercial sex work
–Pregnancy (r/o congenital syphilis)

Testing for Syphilis (Treponemal vs. Non-Treponemal)

–BOTH type of tests required due to risk of false positives and false negatives (eg: immunosuppression/early disease)
-Can use direct visualization tests like DFA or Darkfield Microscopy but SEROLOGY is the most common method of testing.

Non-Treponemal testing

-Based on reactivity of serum of infected patients to a cardiolipin-cholesterol-lecithin antigen but non-specific
-Positive results are reported as a TITER (eg: 1:32) and wane over time with treatment 

–RPR (Rapid Plasma Reagin)
–VDRL (Veneral Disease Research Laboratory)
–TRUST (Toluidine Red Unheated Serum Test)

Treponemal testing

-Directly evaluating for antibodies against Treponemal antigens(higher specificity)!
-Qualitative only (no titers!)  and remain positive for life

–FTA-ABS (Fluorescent Treponemal antibody absorption)
–TPPA (T.Pallidum particle agglutination assay)
–EIA (Enzyme immunoassay)
–CIA (Chemiluminsence immunoassay)

At VMC, our policy is to do a Treponemal test (EIA) and confirm with a Non-Treponemal test (RPR with titer)

What if you suspect Neurosyphilis

-Must do LP and classically see elevated lymphocytes and protein on CSF
–(+) VDRL in CSF is highly specific for neurosyphilis but poor sensitivity (can be negative in up to 70 % of cases!)
–If negative VDRL, can check FTA-ABS (higher sensitivity/poor specificity)

Clinical manifestations of Neurosyphilis

EARLY neurosyphilis

• Asymptomatic! (+) CSF VDRL
• Meningitis, cranial neuropathies
• Syphilitic gummas (can occur any
• Ocular syphilis/Oto-syphilis

LATE neurosyphilis

• General paresis (General paralysis of the insane)-10 % of psych admissions prior to 1928
• Tabes Dorsalis (posterior columns/dorsal roots)- + Argyll-Robertson pupil

Treatment of Neurosyphilis

• Aqueous IV Pencillin G 4 million units q4h x 10-14d

Etiology of Acquired PRCA (can also be congenital) 

–IDIOPATHIC (most common)
-Drugs (Phenytoin, Bactrim, Zidovudine, Mycophenolate, INH etc.)
-Infections (Parvovirus B19, HIV, Viral Hepatitis)
–Auto-Immune (SLE, RA, auto-immune hemolytic anemia, ABO incompatible HCT, Epo treatment)
–Lymphoid malignancies (CLL, HL, NHL, Myeloma)
–Myeloid malignancies (CML, myelodysplastic syndrome, other cancers)
-Thymoma
–Pregnancy

Making the Diagnosis of PRCA (all 4 criteria must be met)

• Normocytic Normochromic anemia
• Very low or zero reticulocyte count with ARC <10,000/microL
• NORMAL WBC count and platelet count

Bone Marrow Biopsy: Normocellular bone marrow with normal myeloid, lymphoid, and megakaryocytopoiesis but minimal erythroid precursors

LOW reticulocyte count=reduced bone marrow response

• AOCD, mild/moderate IDA, renal failure, PRCA

HIGH reticulocyte count=preserved bone marrow response

• Hemolysis, bleeding, Sickle cell, RBC membrane disorders

General treatment of PRCA 

-RBC transfusion for symptomatic anemia
-STOP any possible offending drugs (see above)
-Search and treat any associated conditions
–Immunosuppression (Glucocorticoids/Cyclosporine/Cyclophosphamide etc)

Specific Treatment for Parvovirus B19 related PRCA

–Immunocompetent (usually spontaneous resolution within 2-3 weeks)
–Immunocompromised (Usually will not spontaneously resolve and can develop chronic infection) Treatment of choice is IVIG