Dermatologic manifestations in patients w/ systemic disease Flashcards
1
Q
What are the cutaneous findings in Behçet’s disease?
A
Orogenital aphthous ulcers, pustular vasculitis, and pathergy
2
Q
What systemic manifestations are seen in Behçet’s disease?
A
A/w pericarditis, coronary arteritis, valve disease, CNS vasculitis, and ocular disease (e.g. vasculitis, uveitis [panuveitis > posterior uveitis > anterior uveitis], vitritis, retinitis)
3
Q
What are the cutaneous findings of Birt-Hogg-Dubé syndrome?
A
Fibrofolliculomas, trichodiscomas, perifollicular fibromas, and acrochordons; lesions most commonly affect head/neck; lesions tend to present in 30s–40s
4
Q
What are the genetics of Birt-Hogg-Dubé syndrome?
A
Folliculin (FLCN) mutations (involved in mTOR signaling)
5
Q
What are the associations seen in Birt-Hogg-Dubé syndrome?
A
- Pulmonary cysts (most common; up to 90%) lead to spontaneous pneumothorax (30%)
- Multiple renal carcinomas (15%, most commonly chromophobe renal carcinoma and oncocytoma)
- Medullary thyroid cancers
- +/- colon cancer
6
Q
Cutaneous findings of Cardio-facio-cutaneous syndrome?
A
Coarse facies (long and broad), generalized ichthyosis- like scaling, keratosis pilaris, CALMs, nevi, and sparse curly hair
7
Q
Genetics of Cardio-facio-cutaneous syndrome?
A
AD; RASopathy, mutations in BRAF (most commonly) and other MAPK mutations
8
Q
Assocations of Cardio-facio-cutaneous syndrome?
A
- A/w mental retardation, pulmonic stenosis, atrial septal defect, hypertrophic cardiomyopathy, and short stature
- All RASopathies (CFC, NF1, Noonan, Costello syndromes, and LEOPARD) affect RAS/MAPK pathway and have similar clinical presentations → often need genetic tests to distinguish
9
Q
Cutaneous findings in Carney complex (LAMB/NAME syndromes)?
A
LAMB = Lentigines, Atrial (and cutaneous) Myxomas, Blue nevi (classically epithelioid blue nevi)
NAME = Nevi, Atrial (and cutaneous) Myxomas, Ephelides
10
Q
Genetics of Carney complex (LAMB/NAME syndromes)?
A
AD, mutations in PRKAR1A gene (subunit of protein kinase A)
11
Q
Associations seen in Carney complex (LAMB/NAME syndromes)?
A
A/w variety of endocrine neoplasms;
most commonly affected = adrenal gland; p/w
primary pigmented nodular adrenocortical disease →
Cushing’s
Other endocrine abnormalities: pituitary adenomas and testicular cancer (Sertoli type)
A/w psammomatous melanotic schwannoma
12
Q
What are the cutaneous findings in Carvajal syndrome?
A
Striate epidermolytic palmoplantar keratoderma; wooly scalp hair
13
Q
Genetics of Carvajal syndrome?
A
AR, desmoplakin mutations
14
Q
Associations seen in Carvajal syndrome?
A
A/w dilated left ventricular cardiomyopathy
* Mnemonic: “CarvajaL = Linear/striate PPK + Left ventricular cardiomyopathy”
15
Q
Cutaneous findings of Churg-Strauss syndrome (allergic granulomatous angiitis)?
A
Skin involvement in 60%; LCV, urticaria, livedo reticularis, subcutaneous nodules, PNGD (palisaded neutrophilic granulomatous dermatitis), and extravascular granulomas
16
Q
Associations of Churg-Strauss syndrome (allergic granulomatous angiitis)?
A
Most commonly a/w allergic rhinitis, severe asthma, peripheral eosinophilia of ≥10%, sinusitis, transient pulmonary infiltrates, and mononeuritis multiplex
- Increased serum IgE levels
- Most common causes of mortality: myocarditis and coronary arteritis
- ANCAs detectable in 50%; p-ANCA (anti-MPO) ≫ c-ANCA (PR-3)
- ANCAs less frequently positive compared with Wegener’s (50% vs ~100%)
- May be a/w leukotriene inhibitors (montelukast and zafirlukast)
17
Q
Cutaneous findings of Costello syndrome?
A
Lax skin on hands and feet, coarse facies, low-set ears, deep palmoplantar creases, periorificial papillomas, acanthosis nigricans, and curly hair
18
Q
Genetics of Costello syndrome?
A
AD, one of the RASopathies; mutations in HRAS (85%) > KRAS (10%–15%)
19
Q
Associations with Costello syndrome?
A
- A/w mental and growth retardation, pulmonic stenosis, hypertrophic cardiomyopathy, and arrhythmias
- Increased risk of rhabdomyosarcoma and transitional cell (bladder) CA
- All RASopathies (CFC, NF1, Noonan, Costello syndromes, and LEOPARD) have similar clinical presentations –> need genetic tests to distinguish
20
Q
Cutaneous findings of cutis laxa?
A
Loose, pendulous skin of face (esp. periocular and cheeks leading to “bloodhound facies”), neck, axillae, and thighs; skin lacks elastic recoil (vs EDS)
21
Q
Genetics of cutis laxa?
A
Multiple forms:
- AR: most common and most severe; Fibulin-5 (FBLN5)
- AD: benign course; Elastin (ELN) > FBLN5 - XLR: ATP7A (copper transporter)
22
Q
Associations of cutis laxa?
A
Occipital horn syndrome is the current name for XLR cutis laxa, (which was also formerly called Ehlers-Danlos type IX); OHS a mild variant of Menkes kinky hair syndrome
- AR cutis laxa is most frequently a/w internal organ dysfunction and death:
Pulmonary: bronchiectasis, emphysema leading to right-sided heart failure
Cardiac: aortic dilation/rupture; right-sided heart failure
GI: diverticulae
23
Q
Associations with dermatomyositis?
A
A/w ECG changes and pericarditis
- Cardiac involvement = poor prognostic sign; a/w
anti-SRP autoantibodies
- Pulmonary fibrosis a/w antisynthetase syndrome (Jo-1, PL7, and PL-12; autoantibodies target tRNA synthetase)
24
Q
Cutaneous findings in Ehler-Danlos syndrome (classic form)?
A
Skin hyperelasticity, “cigarette paper” and “fish mouth” scars, ecchymoses, Gorlin sign, and molluscoid pseudotumors
25
Associations with Ehler-Danlos syndrome (classic form)?
- A/w aortic root dilation, mitral and tricuspid prolapse or regurgitation
- Identical cardiac findings may also be seen in hypermobility type of EDS (traditionally, EDS type III)
26
Cutaneous findings in Ehler-Danlos syndrome (vascular form/type IV)?
Thin, translucent skin w/ visible veins (most prominent on chest), diffuse bruising
27
Genetics of Ehler-Danlos syndrome (vascular form/type IV)?
AD; mutations in collagen III (COL3A1)
28
Associations with Ehler-Danlos syndrome (vascular form/type IV)?
**Most dangerous form of EDS** = risk of death from rupture of internal organs (arterial rupture \> GI tract [esp. sigmoid colon], uterus [particularly in pregnancy])
- Arterial rupture sites: thorax/abdomen \> head/neck\> extermities
- Most important feature is vascular fragility leading to arterial aneurysms, dissection, and rupture (Mnemonic: “IV = vascular”)
29
Cutaneous lesions of endocarditis?
Purpura, Janeway lesions (not painful; palms and soles), Osler’s nodes (painful; “Osler’s = Oww!”; fingers and toes) nail-fold infarction
30
Systemic manifestations of erythroderma?
- A/w high-output cardiac failure
- May be as a result of multiple dermatoses, CTCL, or drug eruptions
31
Cutaneous findings of Fabry disease?
Angiokeratoma corporis diffusum (angiokeratomas in “bathing suit distribution”), hypohidrosis, episodic pain in hands/feet (acroparesthesia), and whorled corneal opacities (cornea verticillata)
32
What are the genetics of Fabry disease?
XLR: GLA mutation leading to alpha-galactosidase deficiency
33
Associations with Fabry disease?
Most serious complications: atherosclerotic disease of CV and CNS leading to MI and stroke; chronic proteinuria leading to renal failure
α-galactosidase deficiency leads to increased globotriaosylceramide deposits in tissues leading to end-organ damage
- “Maltese crosses” (birefringent lipid globules) seen on polarization of urine sediment
34
What are the cutaneous findings of hemochromatosis?
Diffuse bronze hyperpigmentation (melanin)
35
What is the gene mutation in hemochromatosis?
HFE mutation
36
What are the systemic associations with hemochromatosis?
A/w CHF (congestive heart failure), supraventricular arrhythmias, diabetes mellitus, and cirrhosis
37
What are the cutaneous findings of hereditary hemorrhagic telangiectasia?
Multiple macular/“mat-like” telangiectasias most commonly on lips, oral mucosa, and extremities
38
Genetics of hereditary hemorrhagic telangiectasia?
AD, mutations in genes involved in TGF-β transduction pathway:
HHT1 = endoglin (ENG)
HHT2 = Alk-1 (ACVRL1)
39
In what type of hereditary hemorrhagic telangiectasia is pulmonary disease most common in?
Type I \> type II
40
Associations with hereditary hemorrhagic telangiectasia?
Epistaxis (often the initial symptom), AV malformations of lungs (HHT-1 most commonly), liver (HHT-2 most commonly) and CNS; recurrent upper GI hemorrhage
## Footnote
*Mnemonic: “Alk-1 is a/w liver” (think of Alkaline phosphatase, which is found in liver)*
41
What are the cutaneous findings of homocystinuria?
Livedo reticularis, malar rash, tissue-paper scars, diffuse pigment dilution, Marfanoid habitus, and ectopia lentis (downward lens dislocation)
42
Genetics of homocystinuria?
AR; caused by a variety of mutations leading to an increase in homocysteine levels in blood and urine; most common = cystathionine β-synthase (CBS gene)
* Other gene mutations: MTHFR, MTR, MTRR, and MMADHC
43
Associations with homocystinuria?
- A/w atherosclerosis and vascular thrombosis (arterial + venous)
- A/w mental retardation and seizures
44
What are the cutaneous findings in hyperlipoproteinemia type I?
Type I (familial LPL deficiency and hyperchylomicronemia): eruptive xanthomas
45
What are the cutaneous findings in hyperlipoproteinemia type II?
Type II (familial hypercholesterolemia): tendinous, tuberous, tuboeruptive, interdigital xanthomas (pathognomonic), and plane xanthomas
46
What are the cutaneous findings in hyperlipoproteinemia type III?
Type III (familial dysbetalipoproteinemia, “broad beta disease”): tendinous, tuberous, tuboeruptive xanthomas, and plane xanthomas of palmar creases (pathognomonic)
47
What are the cutaneous findings in hyperlipoproteinemia type IV?
Type IV (endogenous hypertriglyceridemia): eruptive xanthomas
48
What are the cutaneous findings in hyperlipoproteinemia type IV?
Type V: eruptive xanthomas
49
Genetics in hyperlipoproteinemia type I?
Type I: LPL deficiency and ApoC-II deficiency
50
Genetics in hyperlipoproteinemia type II?
Type II: LDL receptor defect and ApoB-100 defect
51
Genetics in hyperlipoproteinemia type III?
Type III: ApoE abnormality (results in decreased hepatic clearance)
52
Genetics in hyperlipoproteinemia type IV?
Type IV: Increased VLDL as a result of diabetes, alcoholism, and/or obesity
53
Genetics in hyperlipoproteinemia type V?
Type V: Increased chylomicrons and VLDL; as a result of diabetes
54
Associations with hyperlipoproteinemias?
Type I, type IV, and type V: acute pancreatitis (as a
result of increased TGs)
Type II and III: atherosclerosis= MI and stroke
55
Cutaneous findings in Kawasaki disease?
“Strawberry tongue,” cheilitis, polymorphous skin eruption (favors trunk), acral erythema/edema (w/ subsequent desquamation), conjunctival injection, and anterior uveitis
56
Associations with Kawasaki disease?
A/w coronary artery aneurysms (potentially fatal)
* High fever lasting ≥5 days, cervical lymphadenopathy, truncal rash, hand edema/desquamation, oral findings, and conjunctival injection are diagnostic features
* Rx: high dose ASA and IVIG are essential to prevent coronary disease
57
Cutaneous findings of LEOPARD syndrome?
Lentigines (upper half of body; appear in childhood), CALMs, ocular hypertelorism (widely spaced eyes), low-set ears
58
Genetics of LEOPARD syndrome?
AD; is one of the RASopathies; most common mutation is PTPN11 gene (90%)
- Less common mutations in MAPK pathway (10%): BRAF and RAF1
59
Associations with LEOPARD syndrome?
ECG abnormalities, pulmonary stenosis, abnormalities of genitalia (cryptorchidism #1, hypospadias), retardation of growth, and deafness
- Hard to clinically distinguish from other RASopathies (CFC, NF1, Noonan, and Costello syndromes)
60
Cutaneous findings of lymphomatoid granulomatosis?
Dermal or SQ nodules +/− ulceration on trunk and extremities
61
Associations with lymphomatoid granulomatosis?
- Frequently fatal (60% 5-year mortality), EBV-induced angiodestructive B-cell lymphoma
Classically p/w pulmonary + skin involvement
62
Cutaneous findings of Marfan syndrome?
Striae, long and narrow face, ectopia lentis (upward lens dislocation), myopia, arachnodactyly, and pectus excavatum
63
Genetics of Marfan syndrome?
AD, fibrillin-1 mutations
64
Associations with Marfan syndrome?
Mitral valve prolapse and regurgitation, aortic root dilation, and dissection of ascending aorta
Rx: β-blockers and ACE inhibitors to prevent aortic root dilation
65
Cutaneous findings of neonatal lupus erythematosus?
Nonscarring, nonatrophic SCLE-like annular plaques (most commonly periocular), and prominent telangiectasias
66
Associations with neonatal lupus erythematosus?
NLE a/w congenital heart block in up to 30% of pts (often irreversible; up to 30% mortality)
Caused by transplacental passage of maternal anti-Ro/ SSA antibodies (\>anti-La/SSB \> anti-U1RNP)
Mothers who have one child w/ NLE have 25% recurrence rate in subsequent pregnancies
67
Cutaneous findings in PHACES syndrome?
Segmental infantile hemangioma (most commonly frontotemporal), typically on face and neck
68
Associations in PHACES syndrome?
A/w coarctation of the aorta, atrial septal defect, and ventricular septal defect
P: posterior fossa malformations
H: hemangiomas
A: arterial anomalies
C: cardiac defects and coarctation of
the aorta
E: eye anomalies
S: sternal defects and supraumbilical raphe
69
Cutaneous findings in Naxos syndrome?
Diffuse nonepidermolytic palmoplantar keratoderma, wooly scalp hair
70
Genetics of Naxos syndrome?
AR, plakoglobin mutation
71
Associations with Naxos syndrome?
A/w arrhythmic right ventricular cardiomyopathy
72
Cutaneous findings in neurofibromatosis type I?
CALMs, axillary freckles (“Crowe’s sign”; seen in 30%; may involve neck and other intertriginous sites), multiple neurofibromas, and Lisch nodules (iris)
73
Genetics to neurofibromatosis type I
AD mutation in NF1 gene (neurofibromin)
74
Associations with neurofibromatosis type I?
HTN (essential and 2/2 pheochromocytoma)
75
Cutaneous findings of primary systemic amyloidosis (AL amyloidosis)?
Petechiae/pinch purpura most common skin finding; may also see shiny, translucent waxy papulonodules or plaques, alopecia, and macroglossia
76
Associations with primary systemic amyloidosis (AL amyloidosis)?
A/w restrictive cardiomyopathy, conduction abnormalities, and proteinuria
- As a result of deposition of immunoglobulin light chains (AL) in skin and internal tissues; deposits stain pink-red w/ Congo red (apple-green birefringence on polarized light)
- Primary systemic amyloidosis a/w skin findings in 30%
77
Does secondary amyloidosis lead to cutaneous findings?
NO
78
Cutaneous findings in progeria?
Sclerodermoid changes, characteristic facies (prominent eyes, thin beaked nose, protruding ears, and micrognathia), mottled hyperpigmentation, decreased SQ fat, andalopecia
79
Genetics of progeria?
AD; mutations in lamin A (LMNA gene; component of nuclear lamina)
80
Associations with progeria?
Most important association: premature death as a result of atherosclerosis, MI, or stroke
81
Associations with psoriasis?
Increased risk of cardiovascular, cerebrovascular, and peripheral arterial diseases; increased risk of metabolic syndrome
82
Cutaneous findings in relapsing polychondritis?
Intense erythema of cartilaginous portion of ears (spares earlobes) + inflammation of other cartilaginous tissues (nose and trachea)
83
Associations in relapsing polychondritis?
- A/w tracheal and nasal collapse
- A/w aortic insufficiency and dissecting aortic aneurysm
84
Cutaneous findings in rheumatic fever?
Erythema marginatum, subcutaneous nodules (similar to rheumatoid nodules), polyarthritis, chorea, and fever
85
Associations with rheumatic fever?
Acute phase: pericarditis
- Chronic: mitral and aortic valve disease
86
Cutaneous findings in sarcoidosis?
Red-brown papules, nodules, and plaques w/ “apple jelly” color on diascopy; may arise in preexisting scars; lupus pernio (strongly a/w lung disease), EN (a/w acute bilateral hilar adenopathy and arthritis of ankles = Lofgren syndrome)
87
Associations with sarcoidosis?
Pulmonary: pulmonary artery HTN and interstitial lung disease
Cardiac: pericarditis and conduction defects; cardiac involvement a/w poor prognosis
88
Cutaneous findings of SLE?
Transient malar erythema; photosensitivity +/− DLE and SCLE lesions
If antiphospholipid antibodies present: necrotizing livedo reticularis, widespread cutaneous necrosis, and leg ulcers
89
Associations with SLE?
A/w Libman-Sacks endocarditis (nonbacterial), pericarditis, and coronary artery disease
90
Cutaneous findings in Wegener's granulomatosis (granulomatosis with polyangiitis)?
Skin involvement in 50%; LCV, necrotizing cutaneous granulomas, pyoderma gangrenosum-like lesions (“malignant pyoderma”), friable ulcerative gingivae (strawberry gingivae), mucosal ulcerations, and “saddle nose”
91
Associations with Wegener's granulomatosis (granulomatosis with polyangiitis)?
Severe (\>90% mortality if untreated) multisystem necrotizing vasculitis
* Most common systemic manifestations: respiratory tract (chronic sinusitis is most common presenting symptom of GPA); renal (segmental crescentic necrotizing glomerulonephritis)
* c-ANCA (anti-Proteinase-3) autoantibodies in ~100% of pts by ELISA and IIF; detectable ANCAs more common in GPA than in Churg-Strauss (50%)
92
Cutaneous findings in Yellow nail syndrome?
Thick, slow-growing, highly curved, and yellow or yellow-green nails w/ onycholysis; absent cuticles and lunulae
93
Classic triad seen in yellow nail syndrome?
Yellow nails, lymphedema, and pulmonary disease (bronchiectasis and pleural effusions)
94
What are the associations with bullous diabeticorum?
Usually heals in 2 to 4 weeks
- M\>F
- Treatment with supportive care
95
Associations with acanthosis nigricans?
Slow onset, usually manifests earlier in life
Can indicate insulin resistance and/or diabetes
More common in darkly pigmented individuals
Treatment includes improvement of insulin resistance,
topical retinoids, ammonium lactate, and calcipotriene
96
Cutaneous findings in granuloma annulare?
Often affects trunks and extensor limbs, or may be generalized and eruptive; p/w nonscaly, flesh-colored, pink, violaceous, or reddish-brown papules that can be grouped in an arcuate or annular pattern
97
Associations with granuloma annulare?
Usually asymptomatic and spontaneously resolves over months to years
DDx: NLD (favors lower legs), cutaneous sarcoidosis, lichen planus, and rheumatoid nodules
Rx: observation, topical steroids, intralesional steroids, cryotherapy, and phototherapy
May also be a/w hyperlipidemia
98
Cutaneous findings in carotenemia?
Diffuse orange-yellow discoloration
99
Cutaneous findings in scleredema diabeticorum?
Erythematous or skin-colored induration of upper back/neck
100
Associations with scleredema diabeticorum?
As a result of glycosaminoglycan deposition
Histology: square biopsy sign, pauci-cellular dermis
(vs increased cellularity in scleromyxedema), and widely spaced collagen bundles separated by mucin (best seen w/ colloidal iron)
May also be associated with Streptococcus infections and IgG-kappa monoclonal gammopathy
101
Cutaneous findings of acral erythema?
Erysipelas-like erythema of the hands and/or feet
102
Associations with acral erythema?
May be secondary to small vessel occlusive disease with compensatory hyperemia
103
What is diabetic dermopathy?
Small, oval, red-brown, atrophic macules and patches that are usually on the lower limbs
104
Associations with diabetic dermopathy?
As a result of minor trauma and/or decreased skin perfusion from microangiopathy
- Early recognition can help detect early presence of renal and retinal microangiopathy
105
Cutaneous findings of necrobiosis lipoidica diabeticorum (NLD)?
Atrophic yellow-orange patches w/ red borders and telangiectasias +/− central ulceration, often on pretibial skin); lesions may ulcerate and heal with atrophic scars
106
Associations with necrobiosis lipoidica diabeticorum (NLD)?
A/w diabetic nephropathy, retinopathy, and smoking
- 30% of NLD pts have diabetes, but only 0.3% of diabetics have NLD
- F\>M
107
Cutaneous lesions seen in MEN type I?
Pituitary gland adenomas, parathyroid tumors, and pancreatic tumors; tuberous sclerosis-like skin changes (collagenomas, facial angiofibromas, leukodermic macules, and CALMs, lipomas)
108
Cutaneous lesions seen in MEN type IIa?
Parathyroid adenomas, medullary thyroid carcinoma, pheochromocytoma notalgia paresthetica, and macular/lichen amyloidosis
109
Cutaneous lesions seen in MEN type IIb/III?
Mucosal neuromas, medullary thyroid carcinoma, pheochromocytoma, GI ganglioneuromatosis, marfanoid habitus, and thickened lips
110
Genetics of the MEN?
AD
Type I: MEN1 (encodes menin, a tumor suppressor)
Types IIa and IIb/III: RET (encodes a tyrosine receptor
kinase)
111
Associations with MEN?
Most important mucocutaneous changes:
* MEN 1 = TS-like changes
* MEN 2a = amyloid
* MEN 2b = mucosal neuromas; marfanoid features
112
Most common infections in diabetes?
Erythrasma
Furuncles/carbuncles
Candidiasis: angular cheilitis, median rhomboid glossitis,
chronic paronychia, erosion interdigitale blastomycetica,
genital infections, and intertrigo
Other bacterial and fungal infections
113
Cutaneous findings in Graves' disease?
Velvety, smooth, or moist skin, Localized or generalized hyperpigmentation, Fine hair; mild but diffuse alopecia, Koilonychia, onycholysis, and clubbing from thyroid acropachy
- Pretibial myxedema: Indurated red-brown pretibial plaques
114
Associations with Graves' disease?
Affects 3–5% of pts with Graves’ disease
* Often occurs after surgical treatment of Graves’ disease
* A/w exophthalmos, thyroid acropachy, clubbing, and trachyonychia
115
Findings in thyroid dermopathy?
Symmetric, nonpitting, yellow to red-brown, waxy papules, nodules, and plaques on upper/lower extremities
116
Cutaneous findings in hypothyroidism?
- Coarse, dry, scaly, cold, boggy, and edematous skin
- Generalized myxedema
- Dull, brittle, and coarse hair; diffuse alopecia
- Madarosis (loss of eyebrows/eyelashes), hypohidrosis, onycholysis, and striated/brittle/slow-growing nails
- Cutaneous pallor or yellowing of skin secondary to carotenemia
- Thickened skin with enlargement of the lips and tongue
117
What is the most common thyroid cancer to present as skin metastasis?
Papillary thyroid carcinoma
118
What conditions are associated with thyroid cancers?
- Medullary thyroid carcinoma: MEN IIA, MEN IIB, and Birt-Hogg-Dubé
- Follicular thyroid carcinoma: Cowden syndrome
119
Cutaneous findings in Addison's disease?
Diffuse hyperpigmentation (accentuated in sun-exposed areas) secondary to ACTH secretion; fibrosis and calcification of cartilage; loss of ambisexual hair in postpubertal women
120
Cutaneous findings of Cushing's syndrome?
Thin atrophic skin, easy bruising and poor wound healing, violaceous striae, buffalo hump, moon facies, steroid-induced acne, and hypertrichosis
121
What are the cutaneous findings of Bannayan-Riley-Ruvalcaba syndrome?
Macrocephaly, lipomas, and penile lentigines
122
Genetics of Bannayan-Riley-Ruvalcaba syndrome?
AD, mutation in PTEN gene (encodes protein phosphatase); affects mTOR pathway
123
Associations with Bannayan-Riley-Ruvalcaba syndrome?
Mild phenotypic variant of Cowden syndrome (much lower risk of visceral malignancy)
A/w intestinal hamartomatous polyposis
124
What are the genetics of blue rubber bleb nevus syndrome?
Sporadic (\>AD)
125
Associations with blue rubber bleb nevus syndrome?
Most important and common internal manifestation = **GI venous malformations** (blue blebs) lead to GI hemorrhage (potentially fatal)
Skin lesions precede GI involvement (birth vs early adulthood, respectively) so early recognition of skin changes is important!
126
What are the cutaneous findings of Bowel-associated dermatosis-arthritis syndrome (BADAS, bowel bypass syndrome)?
Erythematous macules and patches with overlying papulovesicles and pustules on proximal extremities and trunk
127
Associations with Bowel-associated dermatosis-arthritis syndrome (BADAS, bowel bypass syndrome)?
P/w fevers, chills, malaise, arthritis, and skin findings
- As a result of bowel bacterial overgrowth leading to complement activation and deposition of antibody complexes in skin/synovium
- 20% are a/w jejunoileal bypass surgery for obesity
- May be a/w IBD
- Rx: antibiotics (TCN, quinolones, metronidazole, and macrolides) and topical steroids; consider surgical revision of bowel bypass if severe
128
What cutaneous findings are seen in cirrhosis?
Spider angiomas, palmar erythema, gynecomastia, Terry’s nails (liver failure), Muehrcke’s nails (hypoalbuminemia), pruritus, and jaundice
129
Cutaneous findings of Cowden syndrome (PTEN hamartoma syndrome)
Facial trichilemmomas, oral papillomas (tongue, gingivae most commonly), palmoplantar keratoses, multiple lipomas, **sclerotic fibromas** (pathognomonic), and penile lentigines
130
Genetics of Cowden syndrome?
AD, mutation in PTEN (encodes protein phosphatase); affects mTOR pathway
131
What non-cancerous associations are seen with Cowden syndrome?
A/w hamartomatous polyps in GI tract, fibrocystic breast disease
PTEN Hamartoma syndrome (PTHS): umbrella term encompassing Cowden’s syndrome, Bannayan-Riley- Ruvalcaba syndrome, PTEN-related Proteus syndrome, and Proteus-like syndrome; all diseases have overlapping features
132
What is Lhermitte Duclos disease?
Part of Cowden's disease: Dysplastic gangliocytoma of the cerebellum (hamartoma) leads to cerebellar ataxia, macrocephaly, and increased intracranial pressure
133
Cutaneous findings in Cronkhite-Canada syndrome?
Lentiginous hypermelanosis, alopecia, and nail thinning
134
Associations in Cronkhite-Canada syndrome?
A/w nonhereditary adenomatous polyposis, diarrhea/ malabsorption (leading to weight loss), edema, and abdominal pain
No increased risk of cancer
135
What are the cutaneous findings of Dego's disease?
Eruption of multiple papules with porcelain-white center and erythematous rim; most commonly affects upper extremities and trunk
136
Associations with Dego's disease?
Is an occlusive vasculopathy of small arteries w/ poor prognosis (exception: skin-limited form has good prognosis)
A/w **GI perforation** (most common and most severe complication; occurs in half of cases; high mortality) \> CNS disease
137
Genetics of dermatitis herpetiformis?
Associated with: **HLA-DQ2 \> HLA-DQ8** \>\> other cited haplotypes (HLA-A1, HLA-B8, HLA-DR3)
138
Associations with dermatitis herpetiformis?
Very strong association with gluten-sensitive enteropathy/ celiac disease
• Poor adherence to gluten-free diet → ↑risk GI lymphoma
139
Cutaneous findings of Gardner syndrome?
Multiple epidermoid cysts (often hybrid cysts w/ focal pilomatrical differentiation), multiple pilomatricomas, multiple lipomas, desmoid tumors (15%), fibromas, jaw osteomas, and odontogenic cysts
140
What are the genetics of Gardner syndrome?
AD mutation in APC gene (normally functions to downregulate β-catenin)
(This is a phenotypic variant of familial adenomatous polyposis syndrome)
141
Associations with Gardner's syndrome?
- A/w many neoplasms: **colorectal (~100%) carcinoma**
- A/w congenital hypertrophy of retinal pigment epithelium (CHRPE)
- Syndromes a/w multiple pilomatricomas: Gardner, Rubenstein-Taybi, myotonic dystrophy
- Syndromes a/w multiple lipomas: Gardner, Bannayan-Riley-Ruvalcaba, and MEN-I
142
What syndromes are associated with multiple pilomatrixicomas?
Gardner, Rubenstein-Taybi, myotonic dystrophy
143
What syndromes are associated with multiple lipomas?
Gardner, Bannayan-Riley-Ruvalcaba, and MEN-I
144
Cutaneous findings in hemochromatosis?
Generalized bronzing and hyperpigmentation (increased melanin deposition)
145
Genetics of hemochromatosis?
HFE gene mutation (C282Y most common)
146
Associations and tx of hemochromatosis?
A/w excess iron stores, cirrhosis, cardiac dysfunction, and diabetes mellitus
Rx: phlebotomy (first line) and chelation (second line)
147
What are the most important hepatitis B associated diseases?
Gianotti-Crosti (B ≫ C)
Classic PAN (B \> C)
EN (B \>C)
148
What are the most important hepatitis C related diseases?
Necrolytic acral erythema (C)
Erosive oral LP (C)
Cryoglobulinemia types 2 and 3 (C ≫B)
PCT (C \>B)
Cutaneous PAN (C \> B)
Sarcoidosis a/w IFN or ribavirin (C \> B)
149
What diseases are caused by both hepatitis B and C together?
EM, CSSV, pruritus, urticarial vasculitis, and urticaria
150
Associations with inflammatory bowel disease?
A/w erythema nodosum, urticarial vasculitis, small vessel vasculitis, PAN, bowel-associated dermatosis-arthritis syndrome, pyoderma gangrenosum, neutrophilic dermatosis, pyostomatitis vegetans, aphthous ulcers, granulomatous infiltrates, fissures, fistulas, and epidermolysis bullosa acquisita
151
Cutaneous findings of primary biliary cirrhosis?
Pruritus, jaundice, diffuse hyperpigmentation, and xanthomas
152
Associations with primary biliary cirrhosis?
Autoimmune disease strongly a/w antimitochondrial antibodies (\>90%)
F≫M (9:1)
Osteoporosis is common complication
Rx: ursodiol, colchicine, methotrexate, and transplant
153
Cutaneous findings with Peutz-Jeghers syndrome?
Mucosal (\> cutaneous) melanotic macules
154
Genetics of Peutz-Jeghers syndrome?
AD, STK11 mutations
155
Associations with Peutz-Jeghers syndrome?
Benign hamartomatous polyps of the digestive tract (minimal to no malignant potential)
Most important associated malignancies: **breast** (~50%) \> **GI** (~40%) and **pancreatic** (~35%–40%)
156
Cutaneous findings in pseudoxanthoma elasticum?
Yellow papules in intertriginous areas, along with redundant, lax skin
157
Genetics of pseudoxanthoma elasticum?
AR ABCC6 gene mutation (ABC transporter/ATPase involved in multidrug resistance)
158
Associations with pseudoxanthoma elasticum?
A/w GI hemorrhage, angioid streaks (small breaks in Bruch’s membrane), hypertension, premature atherosclerosis, MI, uterine hemorrhage, and vascular calcification
* Angioid streaks a/w: PXE, Paget’s bone disease, sickle cell anemia, and lead poisoning
159
Cutaneous findings in pyoderma gangrenosum?
Violaceous nodule or hemorrhagic pustule that progresses to an ulcer with undermined purpuric borders; ulcer base may be purulent and hemorrhagic with necrotic eschar
- ulcers heal with cribriform scarring
- most commonly affects lower extremities
160
Associations with pyoderma gangrenosum?
A/w IBD (ulcerative colitis \> Crohn’s disease), rheumatoid arthritis, and myeloid blood dyscrasias
Can show pathergy
161
What are the cutaneous findings of pyodermatitis/pyostomatitis vegetans?
Pustules and ulcerations on lips, buccal mucosa, and skin folds
A/w pyoderma gangrenosum of the skin
162
Associations with pyodermatitis/pyostomatitis vegetans?
Almost always a/w IBD (ulcerative colitis \> Crohn’s disease)
Rx: Treat underlying IBD; may use topical steroids or tacrolimus for local control
163
Cutaneous findings of Muir-Torre syndrome?
- Multiple sebaceous neoplasms: sebaceous adenoma, sebaceoma, and sebaceous carcinomas
- Multiple keratoacanthomas (often w/ sebaceous differentiation)
164
Genetics of Muir-Torre syndrome?
AD, mutations in mismatch repair genes leading to microsatellite instability; most common mutations: **MSH2 (90%)** \> MSH6, MLH1, and PMS-2
165
What disease is Muir-Torre syndrome related to?
It is a phenotypic variant of Lynch Syndrome
166
Associations of Muir-Torre syndrome?
Cancer associations: **colon** (most common, 50%) \> GU (second most common) \> gastric, ovarian, endometrial cancers, and lymphoma
* **Extrafacial sebaceous neoplasms are very strongly a/w Muir-Torre (more so than facial lesions)**
* KAs w/ sebaceous differentiation strongly a/w Muir-Torre
167
Cutaneous findings of scleroderma?
Early bilateral edema of hands progressing to acrosclerosis, dermal sclerosis (most commonly arms and head/neck); also see Raynaud phenomenon w/ digital infarction, ventral pterygium, facial telangiectasias (esp. CREST variant), and “salt and pepper” dyspigmentation; dermoscopy of nail folds show dilated capillary loops w/ surrounding avascular areas
168
Associations with scleroderma?
Dermal sclerosis as a result of TGF-β (and endothelin-1, PDGF, IL-4, and connective tissue growth factor)
* Most commonly a/w esophageal dysmotility and pulmonary fibrosis (up to 60%)
* Anti-topoisomerase I (Scl-70): a/w diffuse SSc and pulmonary fibrosis
* Anticentromere antibodies: a/w CREST syndrome (lSSc), and decreased pulmonary, cardiac, and renal involvement
* Anti-PM/Scl antibodies: a/w polymyositis-scleroderma overlap syndrome
169
Cutaneous findings in vitamin C deficiency (scurvy)?
Perifollicular purpura, “corkscrew hairs,” follicular hyperkeratosis, gingivitis, conjunctival hemorrhage, anemia (from GI blood loss), and difficulty walking
170
Association with vitamin C deficiency (scurvy)?
A/w fad diets, malnutrition, and alcoholism
Vitamin C (ascorbic acid) is cofactor for lysyl
hydroxylase and prolyl hydroxylase (required for collagen hydroxylation and subsequent cross-linking) leads to defective collagen cross-linking leading to bone deformities, vascular fragility, poor wound healing, and aforementioned skin findings
171
Associations with spider angioma?
Occurs secondary to hyperestrogenism
Develops in at least 75% of those with cirrhosis; also can occur with pregnancy and oral contraceptive use
172
Cutaneous findings in Wilson's disease?
Kayser-Fleischer rings, blue lunulae, and pretibial hyperpigmentation
173
Genetics of Wilson's disease?
AR mutation in ATP7B
174
Association with Wilson's disease?
Defects in copper metabolism leads to deposition in liver and subsequent liver failure
Neuropsychiatric symptoms common
Ceruloplasmin levels low
Kayser-Fleischer rings as a result of copper deposition in
Descemet’s membrane (cornea)
Rx: penicillamine, trientine, or liver transplantation
175
Associations with calciphylaxis?
As a result of small to medium vessel calcification + thrombosis
* Most commonly occurs in the setting of end-stage renal disease (a/w increased calcium-phosphate product) Other causes: diabetes mellitus and hyperparathyroidism
* A/w secondary infections and sepsis; high mortality * Rx: treat underlying renal failure, partial parathyroidectomy, debride necrotic tissue, sodium thiosulfate, and treat underlying infections; Mayo Clinic has reported success w/ fibrinolytic therapies
176
Cutaneous findings in end-stage renal disease?
Pale color, yellowing of skin secondary to deposition of carotenoids and urochrome, photo-distributed hyperpigmentation, ecchymoses, xerosis, and Lindsay’s (half and half) nails
177
Dermatology associations with end-stage renal disease?
Pruritus, calciphylaxis, metastatic calcification, nephrogenic fibrosing dermopathy/NSF (a/w gadolinium exposure), perforating diseases, uremic frost, pseudoporphyria, and porphyria cutanea tarda
178
Associations with Henoch-Schonlein purpura?
May be a/w IgA glomerulonephritis
Most common in prepubescent children; the majority of pts
Can have preceding URTI/pharyngitis; group A Streptococcus
Is most commonly associated infection
P/w abdominal pain, scrotal pain/edema, arthritis, and transient renal insufficiency (may have chronic renal insufficiency in up to 10%–20%, but only 2% develop ESRD)
179
What organ is also commonly associated with inflammation in HSP?
The testes (can be painful, but not have skin lesions. Can mimic torsion)
180
Cutaneous findings in nail-patella syndrome?
Hypoplasia of nails (fingernails \> toenails; thumb most severely affected), triangular lunulae
181
Genetics of nail-patella syndrome?
AD LMX1B gene mutation (regulates collagen synthesis)
182
Associations with nail-patella syndrome?
A/w focal segmental glomerulosclerosis (seen in 40%, fatal in 10%; important to treat early to prevent renal failure), absence/hypoplasia of patella (90%), iliac horns (pathognomonic exostoses of iliac bone of pelvis, seen in 80%; asymptomatic)
Classic eye finding: Lester iris (~50%; hyperpigmentation of pupillary margin of iris)
183
Cutaneous findings of nephrogenic systemic fibrosis?
Woody, indurated plaques most commonly on legs (\> trunk) with “peau d’orange” appearance; face spared and yellow papules on palms
184
Associations with nephrogenic systemic fibrosis?
All pts have history of exposure to gadolinium MRI contrast dye (highest risk w/ Omniscan, Magnevist, and Optimark) in setting of renal insufficiency (chronic \> acute)
Important eye finding: yellow scleral plaques
185
What are associated with polyarteritis nodosa?
Renal artery aneurysms and HTN
186
What are the cutaneous findings in Reed's Syndrome?
Multiple cutaneous pilar leiomyomas and uterine leiomyomas
187
Genetics of Reed's syndrome?
AD, fumarate hydratase gene mutation
* Fumarate hydratase is an enzyme involved in citric acid/Krebs cycle of cellular respiration
188
Associations with Reed's syndrome?
Increased risk of renal cell carcinoma (15% lifetime risk) and renal cysts
189
Cutaneous findings in tuberous sclerosis?
Facial angiofibromas in butterfly distribution (adenoma sebaceum), periungual and subungual angiofibromas (Koenen’s tumors), ash leaf macules, shagreen patch (back/neck most common), CALMs, and ocular lesions (coloboma and phakoma)
190
Genetics of tuberous sclerosis?
AD; caused by mutations in TSC1 (hamartin) and TSC2 (tuberin)
191
Associations with tuberous sclerosis?
A/w renal angiomyolipomas, CNS tumors (giant cell astrocytoma, cortical tubers, subependymal nodules), mental retardation, seizures, and cardiac rhabdomyomas
192
Cutaneous findings of acquired angioedema?
Painless, nonpitting, pruritic edema of the skin; no associated urticarial plaques/skin lesions
193
Associations with acquired angioedema?
Caused by decreased C1-INH activity (common to all forms of HAE and AAE)
Both types AAE (AAE1 and AAE2) have decreased C1q (distinguishes from HAE) and decreased C2/C4
AAE type 1 a/w lymphoproliferative disease
AAE type 2 a/w autoimmune disease
194
Cutaneous findings of acquired ichthyosis?
Adherent polygonal scale/keratosis on lower extremities (favors extensors); spares flexural creases
195
Associations acquired ichthyosis?
Most commonly a/w Hodgkin and non-Hodgkin lymphoma
Other associations: sarcoidosis, lupus, thyroid dysfunction, drugs, lymphoma, breast and lung cancer
Usually diagnosed after malignancy and course follows that of underlying malignancy
196
Cutaneous findings in acrokeratosis paraneoplastica?
Initially, p/w symmetric erythematous to violaceous psoriasiform plaques on nasal bridge, helices, distal extremities, +/− palmoplantar keratoderma; eruption gradually extends proximally to knees, legs, arms, and scalp
- Other clinical findings include xanthonychia, subungual hyperkeratosis, onycholysis, and horizontal and longitudinal nail ridging
(seen in 75%)
197
Associations with acrokeratosis paraneoplastica?
- Most commonly a/w cancer of **upper aerodigestive tract** (oral cavity, pharynx, larynx, esophagus)
- Can clinically resemble psoriasis (involvement of helices and nose is a clue to Bazex)
- M\>F;averageage=40
- Skin findings precede the diagnosis by 2–6 months
198
Cutaneous findings of alopecia neoplastica?
Localized scarring alopecia as a result of dermal infiltration by metastatic carcinoma
199
Associations w/ alopecia neoplastica?
Metastatic breast cancer
200
Associations with antiepiligrin cicatricial pemphigoid?
A/w variety of adenocarcinomas (**GI and lung** \> gynecologic and GU \> others)
201
Cutaneous findings of carcinoid syndrome?
Head, neck, and upper trunk flushing and erythema; pellagra-like dermatitis, diarrhea, dyspnea, wheezing, and bronchospasm; sclerodermoid changes in advanced disease
202
Associations with carcinoid syndrome?
Increased 5-HIAA levels can be found in urine
* Metastasis to liver is typically required for midgut tumors to produce carcinoid syndrome
* Bronchial and gastric carcinoid tumors may cause flushing in absence of liver metastases
* Although the appendix is the most common location
for primary carcinoid tumors, it very rarely metastasizes to liver so it rarely causes carcinoid syndrome
203
Cutaneous findings in carcinoma en cuirasse/carcinoma erysipeloides?
Carcinoma en cuirasse: indurated skin w/ orange peel-like (peau d’orange) appearance
Carcinoma erysipeloides: well-demarcated, raised red plaque
Both typically present on the chest wall, but can also involve axilla and upper extremities
204
Associations with carcinoma en cuirasse/carcinoma erysipeloides?
As a result of metastatic breast carcinoma infiltration into lymphatic vessels
205
Cutaneous findings in cryoglobulinemia type I?
Retiform purpura and necrosis on cool acral sites; acral cyanosis and livedo reticularis
206
Associations of cryoglobulinemia type I?
As a result of monoclonal gammopathy (typically in the form of a plasma cell dyscrasia such as multiple myeloma, B-cell lymphoma or Waldenström macroglobulinemia)
Histology: vessels plugged with pink proteinaceous material (immunoglobulins)
207
Appearance of cutaneous metastasis?
Erythematous and violaceous papules and nodules
208
Associations with cutaneous metastasis?
Cutaneous metastases occur most commonly from **breast cancer in women and lung cancer in men**
Other cancers with a high cutaneous metastatic potential include: colon, melanoma, and larynx/oral cavity/nasal sinus
Metastases from **renal carcinoma** appear as highly vascular papules and nodules on the **head/neck**
209
Cancers associated with dermatomyositis?
Most commonly a/w ovarian cancer
Other associated malignancies: lung, colorectal pancreatic, and non-Hodgkin lymphoma
210
Cutaneous findings in ectopic ACTH syndrome?
Generalized hyperpigmentation
211
Associations in ectopic ACTH syndrome?
Secondary to tumor production of ACTH (often small cell carcinoma of the lung)
May show features of Cushing’s syndrome
212
Cutaneous findings in erythema gyratum repens?
Widespread serpiginous, polycyclic, and pruriginous erythema with desquamating edges that produce concentric figures (“woodgrain” pattern)
- spares hands and feet
213
Associations with erythema gyratum repens?
**Lung cancer** is most commonly associated malignancy (\> esophageal and breast)
* Usually precedes the detection of primary malignancy and resolves w/ treatment of underlying malignancy
* Average age = 60s; M \> F (2:1)
* Plaques **expand rapidly (~1 cm/day)**
214
What cancers can erythroderma be associated with?
Underlying leukemias and lymphomas
215
Cutaneous appearance of extramammary Paget disease?
Red and white macerated/eroded plaques (“strawberries and cream”) located around anal verge and below dentate line; most common sites are vulva (women) and perianal regions (men)
216
Associations with extramammary Paget disease?
Primary EMPD (\>75%): primary cutaneous adenocarcinoma; likely derived from **Toker cells or cutaneous adnexal glandular epithelium (sweat glands)**; ++− immunophenotype: CK7 , GCFDP-15 , and CK20
Secondary EMPD (20%): may be as a result of direct extension or epidermotropic metastases of underlying GI/GU (\> prostate, ovarian, and endometrial) +− adenocarcinoma; immunophenotype: CK7 / , GCFDP- −+ 15 , and CK20
High rate of recurrence, even w/Mohs (because it is difficult to see individual Paget cells on frozen H&E sections); Mohs with CK7 immunostaining has improved cure rates (\>95%); may try CO2 laser ablation, radiotherapy, imiquimod, or 5-FU
**Five times increased risk of internal malignancy w/ perianal EMPD vs vulvar and penoscrotal**
217
What is the diagnostic criteria for familial atypical mole and multiple melanoma syndrome?
- Numerous (\>50) melanocytic nevi, some of which are clinically dysplastic
- Some nevi are histologically atypical
- Family history of melanoma in one or more first-degree relatives
218
Genetics of Familial atypical mole and multiple melanoma syndrome?
AD; CDKN2A gene mutation (encodes two separate tumor suppressor proteins: p16 and p14/ARF)
p16 inhibits CDK4
p14/ARF inhibits MDM2 (normally degrades p53) in normal state p14 indirectly increases p53 expression
219
Risk if cancer in Familial atypical mole and multiple melanoma syndrome?
Increased risk of melanoma and **pancreatic cancer**
220
Cutaneous findings in Howell-Evans syndrome?
Diffuse waxy keratoderma of high pressure areas on plantar surface (i.e. heel, ball of foot) oral leukokeratosis
221
Genetics of Howell-Evans syndrome?
AD, mutation of “TOC gene” on chromosome 17q25 (gene renamed RHBDF2)
222
Cancer associated with Howell-Evans syndrome?
Esophageal carcinoma
223
Cutaneous findings in hypertrichosis lanuginosa acquisita?
Sudden onset of long, thin, soft, lanugo-like hair initially on the face and ears, which can spread in craniocaudal manner
224
Associations with Hypertrichosis lanuginosa acquisita?
A/w lung, colorectal, and breast cancer; anorexia nervosa
* F \> M (3:1); average age 40–70 years
* Tumor treatment usually leads to regression of hair growth
225
Association seen with juvenile xanthogranuloma and neurofibromatosis type I?
Triple association w/ juvenile xanthogranuloma, neurofibromatosis type 1, and juvenile myelomonocytic leukemia
226
Associations seen with sign of leser-Trélat?
Most commonly a/w underlying gastric adenocarcinoma (\> colon, breast, others)
A/w pruritus and inflammation; may improve with treatment of underlying malignancy
May be a/w acanthosis nigricans and tripe palms
227
Cutaneous findings of malignant acanthosis nigricans?
Sudden onset with extensive and severe lesions; p/w symmetric hyperpigmented velvety plaques typically in intertriginous areas
228
Associations seen with malignant acanthosis nigricans?
Typically a/w **GI cancer** (esp. stomach)
Can occur simultaneously, before, or after cancer
diagnosis and can have associated weight loss
- Improves with treatment of underlying malignancy
25% of patients also have tripe palms (tripe palms in
absence of AN is more commonly a/w lung cancer)
229
Cutaneous findings in multicentric reticulohistocytosis?
Multiple red to red-brown, nontender papules and nodules primarily on dorsal hands and nail folds with a “coral-beaded” appearance; face (esp. ears and perinasal) is second most common site
230
Associations with multicentric reticulohistiocytosis?
- Up to 50% have arthritis mutilans
25%–33% have underlying malignancy (no specific internal malignancy favored); skin eruption usually precedes the diagnosis of internal malignancy
231
Cutaneous findings in necrolytic migratory erythema?
Arcuate and polycyclic, erosive, erythematous patches +/− vesicles/bullae often on genital region, buttocks/ anal region, lower extremities, and intertriginous areas
232
Associations in necrolytic migratory erythema?
Glucagonoma syndrome consists of NME, glucose intolerance, weight loss, glossitis, and glucagon-secreting carcinoma
* A/w pancreatic islet cell carcinoma (α-2 glucagon)
233
Cutaneous findings of necrobiotic xanthogranuloma?
Indurated yellow plaques w/ frequent ulceration and necrosis; most commonly periorbital
234
Associations with necrobiotic xanthogranuloma?
A/w paraproteinemia (most often IgG-κ); occasionally a/w multiple myeloma and other lymphoproliferative malignancies
235
Cutaneous presentation of Paget disease of the breast?
Eczematous and psoriasiform plaques of the nipple
236
Associations seen with Paget disease of the breast?
Almost always a/w underlying ductal breast CA
237
Cutaneous findings in paraneoplastic pemphigus?
Severe erosive disease of mucous membranes leading to painful oral stomatitis; polymorphous bullous skin eruption (individual lesions may resemble EM, LP, PV, or BP)
238
Associations with paraneoplastic pemphigus?
90% mortality; most common causes of death: underlying malignancy, bronchiolitis obliterans, and sepsis
**Most commonly a/w non-Hodgkin lymphoma or CLL**
Other associated malignancies: **Castleman disease (most common association in children)**, thymoma, sarcoma
No gender predominance; usually affects ages
45–70 years
239
Cutaneous findings in pityriasis rotunda?
Multiple well-defined circular hyperpigmented and hypopigmented scaly patches, usually on the trunk/ buttocks
240
Associations with pityriasis rotunda?
Most strongly a/w **hepatocellular carcinoma**
Other associated conditions: tuberculosis, leprosy, and liver and lung disease; gastric and esophageal carcinoma
241
Cutaneous findings of plane xanthoma?
Yellow patches and thin plaques
* Tends to affect trunk, periorbital skin, and body folds
242
Associations seen with plane xanthoma?
Often a/w paraproteinemia, multiple myeloma, and lymphoproliferative malignancies
243
Cutaneous findings in POEMS syndrome?
P: Polyneuropathy (distal to proximal motor and sensory)
* O: Organomegaly
* E: Endocrinopathy (number one is hypogonadism) * M: M-protein (IgG and IgA light chains)
* S: Skin changes
## Footnote
*Most common cutaneous findings: hyperpigmentation (90%), lower extremity edema \>hypertrichosis (80%), sclerodermoid changes \> glomeruloid hemangiomas, cherry angiomas, and nail changes (leukonychia; clubbing) \> acrocyanosis and Raynaud’s*
244
Associations with POEMS syndrome?
Always a/w plasma cell dyscrasia: Waldenstrom macroglobulinemia, osteosclerotic myeloma, MGUS, and Castleman disease
Very increased VEGF levels
Other associated findings include pulmonary effusions, ascites, peripheral edema, polycythemia, and thrombocytosis
245
Associations with systemic primary amyloidosis?
Monoclonal gammopathy most commonly
as a result of plasma cell dyscrasia ≫ multiple myeloma
As a result of deposition of light chains (AL) in various tissues
246
Cutaneous findings in Schnitzler syndrome?
Chronic urticaria in patient with fever, arthralgias, hepatosplenomegaly, and bone pain
247
Associations in Schnitzler syndrome?
A/w IgM-κ paraproteinemia and lymphoplasmacytic malignancies
248
Cutaneous findings in scleromyxedema?
Widespread, firm, waxy papules often arranged in linear fashion; sclerodermoid skin changes; Leonine facies
249
Associations with scleromyxedema?
Invariably a/w paraproteinemia (most commonly IgGλ light chains); progresses to multiple myeloma in 10%
250
What is a Sister Mary Joseph nodule?
Palpable nodule at umbilicus secondary to metastatic tumor
251
Tumors associated with Sister Mary Joseph nodule?
Typically source is a malignancy of pelvis or abdomen including colon, ovarian, and pancreatic uterine and gastric cancer
* Has also been a/w breast cancer
252
Cutaneous findings of sweet syndrome?
“Juicy” red-violaceous papules/plaques that can have overlying pustules and pseudovesicles; favors head/neck, and upper extremities
253
Associations with Sweet syndrome?
F \> M (except in cases a/w underlying malignancy, where M = F)
* Also have fever, malaise, and leukocytosis
* A/w IBD, URI infection, malignancy (most common is AML), and polycythemia vera
* Rx: steroids, potassium iodide, clofazimine, and colchicine
254
Cutaneous manifestation of tripe palms?
Yellow, velvety, diffuse palmar hyperkeratosis with accentuated dermatoglyphic patterns
255
Associations with tripe palms?
Tripe palms + acanthosis nigricans= gastric cancer (most common)
* Tripe palms alone = lung cancer (most common)
256
What malignancies are associated with Cowden's disease?
Lifetime risk of cancer: Breast (85%; often bilateral) \> Thyroid (35%; follicular most common) \> Endometrial
Dysplastic gangliocytoma of the cerebellum (Lhermitte Duclos disease) is a part of Cowden’s syndrome; is a hamartoma that leads to cerebellar ataxia, macrocephaly, and increased intracranial pressure
## Footnote
*Mnemonic: “BET on cancer with Cowden’s”*
