HNG 2024 Flashcards
Pyoderma gangrenosum category
an ulcerative disorder that falls into the category of neutrophilic dermatoses
The most common associated systemic disorders of pyoderma gangrenosum?
rheumatoid arthritis, inflammatory bowel disease, and other autoimmune and inflammatory conditions. Both solid tumors and hematologic malignancies. Pyoderma gangrenosum is associated with ulcerative colitis in 5% to 12% of cases and is associated with Crohn disease in 1% to 2% of cases.
pathogenesis of pyoderma gangrenosum
not fully understood. It is thought to involve genetic mutations, neutrophil dysfunction, and immune/inflammatory dysregulation. Some lesions of pyoderma gangrenosum have been found to have a proliferation of clonal T-cells. In addition, inflammasomes have been postulated to be involved in the neutrophil chemotaxis that occurs in these lesions. Inflammasomes are complexes of receptors that are part of innate immune system signaling. Some cases of pyoderma gangrenosum are associated with a mutation in Janus kinase 2, which is involved in the production of several cytokines. Abnormal cytokine signaling by T cells and macrophages is likely a component of the disease process. Lesions of pyoderma gangrenosum have been found to have increased levels of inflammatory mediators. For example, IL-23 has been found to be increased in lesions of pyoderma gangrenosum. IL-23 is important in activating neutrophils and stimulating IL-17 mediated inflammation
Inflammasomes
Inflammasomes are complexes of receptors that are part of innate immune system signaling.
Histopathology of pyoderma gangrenosum
The disease is a clinical and histologic diagnosis of exclusion as the histologic features are non-specific. The goal of the biopsy is to exclude other causes of ulceration. Early lesions of pyoderma gangrenosum should show an infiltrate of neutrophils in the dermis. Lesions may demonstrate necrotic dermal vessels. Direct immunofluorescence of biopsy specimens of pyoderma gangrenosum is nonspecific.
Sweet syndrome
Sweet syndrome, also called acute febrile neutrophilic dermatosis, is a rare disorder that typically presents with acute-onset tender plaques or nodules, fever, arthralgia, ophthalmologic manifestations, headaches, and rarely, oral or genital lesions.
Pathergy
an exaggerated response to a minor skin injury or worsening of an existing wound with minimal insult or trauma. This has a wide array of implications for the patient including debridement and simple wound care. This also makes the decision to perform certain surgeries and procedures much more difficult. Lastly, insults to the skin that would be nearly meaningless for most people can be devastating for some patients with pyoderma gangrenosum.
Major Criteria of pyoderma gangrenosum
- Rapid progression of a painful, necrolytic cutaneous ulcer with an irregular, violaceous, and undermined border.
- Other causes of cutaneous ulceration have been excluded
Minor Criteria of pyoderma gangrenosum
- History suggestive of pathergy or cribriform scarring
- Systemic diseases associated with pyoderma gangrenosum
- Histopathologic findings (sterile dermal neutrophilia, +/- mixed inflammation, +/- lymphocytic vasculitis)
- Treatment response (rapid response to systemic steroid treatment)
differential diagnosis of pyoderma gangrenosum
infectious diseases like mycobacterial infection and deep fungal infections. Also included in the differential are noninfectious diseases such as iododerma or bromoderma. Other causes of ulcers to consider are arterial ulcers and Martorell ulcers. Arterial ulcers may have associated weakened pulses on the corresponding anatomical side.
What are the risk factors for oral cancer?
Alcohol, smoking, betel nut, immunosuppression, HPV
What are the common sites of oropharyngeal carcinoma?
Underside of tongue and floor of the mouth
What are the 3 layers of a tooth?
Enamel, Dentin, Root
What is the job of the mouth?
Mastication, taste perception, initial starch digestion, swallowing, speech, facial expression.
What role does saliva play in the mouth?
Moistens food, buffers oral contents, protects teeth & mucosa, supplies Ca++ and PO4, neutralize
acid.
calcium phosphate
calcium salt of phosphoric acid with a chemical formula Ca3(PO4)2. It is also known as Calcium phosphate tribasic or Tricalcium Phosphate. Calcium phosphate stones account for approximately 15% of kidney stone disease. Calcium phosphate stones tend to grow in alkaline urine, especially when Proteus bacteria are present.
betel quid
The most common method of using betel nut is to slice it into thin strips and roll it in a betel leaf with slaked lime (powder) or crushed seashells. This leaf package is known as a betel quid, betel nut chew, betel chew, betel pan or betel paan (India)
What is CREST syndrome?
calcinosis cutis, Raynaud’s phenomenon, Esophageal dysmotility, sclerodactyly and telangiectasia,
En coup de sabre
a rare subset of linear morphea. It usually presents as a pan-sclerotic plaque over the frontoparietal scalp with surrounding scarring alopecia. The patients may have central nervous system involvement in addition to the cutaneous findings
Eosinophilic esophagitis histological criteria
Major criteria: ≥ 15 eosinophils per high power field (40x magnification) (Arch Pediatr 2019;26:182)
Minor criteria: extreme basal zone hyperplasia with papillary hyperplasia, eosinophils concentrated in the surface epithelium as opposed to the base, eosinophilic microabscesses, eosinophil degranulation, surface desquamation, lamina propria fibrosis
Eosinophilic esophagitis gross description
Major criteria (Gut 2013;62:489)
Mucosa edema
Exudate or white plaques
Longitudinal furrows
Circular esophageal rings (pseudotrachea)
Esophageal stenosis
Minor criteria (Gut 2013;62:489)
Feline esophagus
Concentric mucosal rings observed with some types of motility that disappear with air insufflation
Narrow caliber esophagus
Crêpe paper esophagus
Mucosal laceration or fragility with passage of instruments before dilation
Helicobacter heilmannii
Very rare compared to H. pylori
More common in children; due to contact with farm animals or household pets
Helical, 3.5 - 7.5 microns, 0.9 microns in diameter
Long tight spirals; thicker and twice as long as H. pylori and usually visible with H&E stain
Autoimmune Hepatitis
ANA, SMA, LKM and/or SLA antibodies
F:M = 7:3
Associated extrahepatic autoimmune disorder: Thyroiditis, Sjogren syndrome, Rheumatoid arthritis.
Hypergammaglobulinemia
Responsive to corticosteroids.
Histo: often sever inflammation and necrosis with abundant plasma cells.
Explain stomach acid control
Two most common causes of peptic ulcer disease
H pylori
NSAIDs
two known types of autoimmune hepatitis
Type 1 is distinguished by the presence of anti-smooth muscle antibodies (ASMA) with or without anti-nuclear antibodies (ANA). Type 2 autoimmune hepatitis presents with positive anti-liver/anti-kidney microsome (anti-LMK) type 1 antibodies or anti-liver cytosol (anti-LC) type 1 antibodies.
Auerbach plexus
Myenteric plexus, between the inner circular and outer longitudinal smooth muscle layers of the muscularis propria.
plexus between the inner circular and outer longitudinal smooth muscle layers of the muscularis propria.
Auerbach plexus. Myenteric plexus.
Dieulafoy lesion
an enlarged (1 to 3 mm) submucosal blood vessel that bleeds in the absence of any abnormality such as ulcers or erosions. The majority of the lesions arise in the stomach at the lesser curvature, within 6 cm of the gastroesophageal junction, as this region receives its arterial blood supply directly from the branches of the left gastric artery
Histopathology of Dieulafoy lesion
A biopsy is not recommended for the diagnosis of Dieulafoy lesions due to an increased risk of bleeding. Dieulafoy lesion can be distinguished from gastric ulcers on histology by a lack of subintimal fibrosis and mucosal inflammation.
Angiodysplasia vs Dieulafoy lesion
Angiodysplasia can be differentiated from Dieulafoy lesions by angiography that reveals the presence of arteriovenous shunting and vascular ectasia; by histological examination of the lesion, which reveals the presence of abnormal submucosal vessels.
Dieulafoy lesion
a normal blood vessel with an abnormally wide diameter of 1 to 3 mm, protruding into the mucosa from the submucosa. The protrusion results in a small wall defect in the gastrointestinal tract with fibrinoid necrosis at the base of the lesion; 70% of these lesions are found in the stomach, usually along the lesser curvature.
the most common causes of granulomas in liver in the US, and worldwide
sarcoidosis and primary biliary cholangitis being the most common causes in the US, and tuberculosis worldwide.
Hepatic granulomas may be classified into four main variants,
caseating, non-caseating, fibrin-ring, and lipogranulomas
Hepatic granulomas fibrin-ring variants
Fibrin-ring variants are epithelioid cells in an encircling fibrin ring with a central vacuole. These fibrin-ring granulomas are seen in infections, may be drug-induced, or in Hodgkin lymphoma. Granulomas in Q fever
Granulomas in Q fever
Granulomas in Q fever are typically characterized by an eosinophilic fibrinoid ring with a central clear space enclosing a fat vacuole.
“pipestem fibrosis”
Schistosomiasis is characterized by progressive portal scarring called “pipestem fibrosis” with marked splenomegaly and variceal hemorrhage.
Pipestem fibrosis liver ultrasound, liver schistosomiasis
How does the schistosomiasis parasite involve the intestines and bladder?
Adult worms migrate against portal blood flow to the mesenteric venules of the small and large intestine (S. japonicum and S. mekongi), the mesenteric venules of the colon (S. mansoni, S. intercalatum) or the vesical venous plexus (S. haematobium)
Migrating eggs elicit a host immune response
Egg derived antigens induce a host Th2 immune response, leading to recruitment of eosinophils, granulomatous reaction and later fibrosis
What type of parasite is schistosomiasis?
trematode blood fluke
trematode
Trematoda is a class of flatworms known as flukes or trematodes.
Calcium in sarcoidosis
Sarcoidosis is also associated with elevated angiotensin-converting enzyme levels and hypercalcemia (due to extrarenal production of 1,25-dihydroxy vitamin D), as seen in this patient. PTH is elevated in primary hyperparathyroidism and PTHrP is elevated in malignancy. TSH is elevated in hypothyroidism.
best test for TB if granulomas in liver
Polymerase chain reaction (PCR) has a sensitivity of 88% and a specificity of 100% in detecting M tuberculosis.
Therapy for primary biliary cholangitis
Polymerase chain reaction (PCR) has a sensitivity of 88% and a specificity of 100% in detecting M tuberculosis.For patients who undergo liver transplantation, outcomes are excellent, with a 1-year survival rate of > 90%. Glucocorticoids are not helpful in the management of primary biliary cholangitis. Penicillamine is used in the treatment of Wilson’s disease.
rare but fatal complication of intravesical BCG.
Granulomatous hepatitis is a rare but fatal complication of intravesical BCG.
Submucosal plexus
Meissner’s nerve plexus
Crypts of Lieberkuhn
crypts in small intestine
Function of Paneth cells in bottom of crypts
Make antimicrobial enzymes (lysozyme and defensins)
Function of Brunner Glands
Make alkaline mucus
Plicae circulares
Jejunum mucosal folds
Celiac Sprue
Autoimmune disease
Intolerance to gliadin in wheat
Anti-endomysial, anti-tissue transglutaminase, and anti-gliadin antibodies.
Histology: blunting and intraepithelial lymphocytes.
HLA-DQ2/SQ8.
Associated with dermatitis herpetiformis.
Whipple Disease. Sex preference
Much more common in males.
Cause of Whipple disease
Tropheryma whipplei.
Intracellular gram + pathogen
Distantly related to Mycobacteria.
PAS-positive foamy macrophage.
Mickel’s diverticulum. Rule of 2’s.
Two inches long.
2% of population.
2 feet from ileocecal valve.
Presents in kids < 2 years.
Pseudomembranous colitis causes
Pseudomembranous colitis results most commonly from C. difficile infections; however, less common etiologies include ischemic colitis, collagenous colitis, inflammatory bowel disease, cytomegalovirus-induced colitis, vasculitis, bacterial and parasitic organisms, Behcet’s Disease, chemotherapeutic medications, and toxins, such as heavy metal poisoning.
The most common cause of infectious diarrhea in healthcare settings,
C. difficile causes substantial morbidity and can potentially result in mortality in vulnerable inpatient populations. C. difficile colonization occurs in 13% of hospitalized patients with stays of 2 weeks and up to 50% of patients with stays more than 4 weeks.
treatment of C. difficile colitis
Although only oral vancomycin and fidaxomicin have US Food and Drug Administration approval for treatment of C. difficile colitis, metronidazole has remained a first-line agent for four decades. Multiple studies document near the equivalent effect of metronidazole with vancomycin for the initial treatment of mild to moderate C. difficile colitis. Because of superior cure rates for severe disease, administer oral vancomycin as first-line treatment of C. difficile colitis. With recurrent C. difficile colitis after oral vancomycin therapy, consider either fidaxomicin or rifaximin oral administration.
esophageal webs / mucosal webs
idiopathic, ledge-like, semi-circumferential mucosal protrusions, can cause non-progressive dysphagia.
rings (Schatzki rings)
circumferential protrusions, thicker than webs, involves mucosa, submucosa, plus or minus muscularis propria.
Zenker diverticulum
most common diverticula, up of upper esophageal sphincter, elderly, weakness in esophageal wall.
epiphrenic diverticulum
immediately above the lower esophageal sphincter, dysfunction of lower esophageal sphincter.
histology of achalasia
loss of ganglion cells, hypertrophic nerves in myenteric plexus.
achalasia has an increased risk of squamous cell carcinoma
etiology of achalasia
most are primary and idiopathic; can be secondary to Chagas disease.
achalasia has an increased risk of squamous cell carcinoma.
differential of white plaques in the esophagus
Candida esophagitis.
Eosinophilic esophagitis.
Glycogenic acanthosis.
Epidermoid metaplasia
histologic criteria for eosinophilic esophagitis
greater than 15 eosinophils per high-power field
Eosinophilic microabscesses are greater than 4 eosinophils clustered.
More eosinophils near the surface (superficial epithelial clustering)
esophagitis dissecans superficialis (sloughing esophagus)
has a healed tissue paper appearance on endoscopy.
Histology: split occurs above the basal cell layer, two-tone appearance of squamous epithelium, parakeratosis, minimal inflammation.
Older adults, associated with polypharmacy, certain medications.
epidermoid metaplasia of the esophagus
esophageal leukoplakia
Middle-aged control.
Associated with smoking and alcohol
Risk of progression to squamous cell carcinoma
Histology: compact hyperorthokeratosis with a prominent granular cell layer and flattened rete.
kayexalate / sodium polystyrene sulfonate
kayexalate / sodium polystyrene sulfonate
Bile acid sequestrant
Sevelamer / Renvela / Renagel
Pill fillers seen in pill esophagitis.
histologic features of reflux esophagitis
Basal cell hyperplasia (> 15% of epithelial thickness)
Dilated intercellular spaces (spongiosis in derm world)
Elongation and congestion of papillae to top third of epithelium.
Extravasated red blood cells/vascular lakes.
Inflammation (+/- eos, T cells, PMNs).
Never out right call “reflux” instead say reflux-type changes.
cancer risk of Barrett’s esophagus with and without dysplasia
0.2 x 0.5% per year for nondysplastic
0.7% for low-grade dysplasia
7% per year for high-grade dysplasia
no established cutoff to make a diagnosis of eosinophilic gastroenteritis. However, the following are the proposed numbers based on reported literature are what?
Stomach: greater than or equal to 30 eosinophils per high-power field in 5 HPF
Duodenum: greater than or equal to 30 eosinophils
Ileum: more than 56 per HPF in the ileum
Right colon: more than 100 per HPF
Transverse and descending colon: more than 84 per HPF
Rectosigmoid colon: more than 64 per HPF
Some of the common diseases associated with eosinophilia include
eosinophilic gastroenteritis, celiac disease, inflammatory bowel disease, infections (parasitic, amebic, fungal), connective tissue disorders, vasculitis, and hypereosinophilic syndrome, for instance. Radiographically, inflammatory bowel disease and lymphoma can mimic eosinophilic gastroenteritis.
In the pediatric group, non-IgE mediated food allergy and infantile hypertrophic pyloric stenosis require exclusion, along with differential diagnoses mentioned above
Alzheimer’s disease
cortex – amyloid plaques and tangles
Parkinson’s disease (PD)
substantia nigra – Lewy bodies
Alpha-synuclein accumulation leading to Lewy Body formation
PD with dementia and dementia with Lewy bodies have Lewy bodies in brainstem and cortex
Hutington’s disease
caudate/putamen –intranuclear inclusions
Huntingtin protein with polyglutamine expansion and accumulation of abnormal protein in neurons of caudate and putamen
Trinucleotide repeat
Autosomal Dominant with paternal anticipation.
Trinucleotide (CAG) repeats expansion in htt gene on chro. 4. Encodes Huntington protien
