Metabolic Dan Flashcards

1
Q

T/F

Hereditary coproporphyria causes skin disease only

A

False

Skin + acute attacks

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2
Q

T/F

Porphyria cutanea tarda (PCT) is the most common type of porphyria

A

True

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3
Q

T/F

Acute intermittent porphyria (AIP) causes acute attacks only

A

True
no skin disease
AIP is alone in this group

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4
Q

Which porphyrias cause skin disease only?

A

Porphyria cutanea tarda (PCT)
Congenital erythropoietic porphyria (CEP)
Erythropoieic protoporphyria (EPP)

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5
Q

Which porphyrias cause skin disease and acute attacks?

A
Hereditary coproporphyria (HC)
Variegate porphyria (VP)
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6
Q

T/F

Porphyrias all result from a total deficiency of one of the enzymes required for the biosynthesis of haem

A

False

from a partial deficiency of one of the enzymes

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7
Q

T/F

‘Bullous porphyrias’ includes all the skin disease causing porphyrias

A

False

EPP causes pain and erythema on sun exposure not bullae

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8
Q

T/F

All of the porphyrias except AIP cause cutaneous disease

A

True

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9
Q

T/F

Porphyrins absorb photons of infrared light, with wavelength peak at 408nm

A

False

visible violet light with peak at 408nm = the Soret band

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10
Q

T/F

Most types of porphyrias are inherited

A

True

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11
Q

T/F

Most patients with an inherited porphyria get symptoms eventually

A

False

Most remain asymptomatic

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12
Q

T/F

Accumulation of hydrophobic porphyrins leads to blistering skin disease on light exposure

A

False

Hydrophilic porphyrins accumulate in skin causing blistering

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13
Q

T/F
Accumulation of lipophilic protoporphyrins leads to an immediate cutaneous burning sensation after exposure to light, accompanied by erythema, and oedema

A

True

this occurs in EPP

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14
Q

T/F

Variegate porphyria causes immediate cutaneous burning sensation after exposure to light

A

False
In VP hydrophilic (uro- and copro-) and hydrophobic (proto-) porphyrins accumulate but the blistering skin disease predominates clinically

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15
Q

T/F

Acute porphyria attack is an acute and potentially fatal illness

A

True

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16
Q

T/F

In liver, a small proportion of available haem is incorporated into cytochrome P450 proteins

A

False

this is the main fate of haem in the liver

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17
Q

T/F

Acute porphyria attacks are caused by penicillins

A

False

not one of the main causes but can be true for individuals

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18
Q

What are the triggers of acute attakcs in porphyrias?

A
FIG BEANS
Fever/
Infection
Griseofulvin
Barbiturates
(o)Estrogen
Alcohol
Nutritional (fasting)
Sulfonamides
Or 
5 M’s 
Medication
Menstruation(Oe) - esp luteal phase of cycle
Maladie
Malnutrition (fasting)
Merlot (alcoholism)
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19
Q

What are the features of acute attacks in porphyrias?

A

6 P’s
Porphobilinogen deaminase deficiency and build up of Porphobilinogen
Precipitated by the 5 M’s
Pain in abdomen – in 95% of cases
Psychological symptoms – anxiety/agitation, hallucination, delirium, depression
Peripheral neuropathy – patchy numbness and paraesthesias
Pee Problems – dysuria, retention, Port-wine (dark purple) urine on standing/UV light

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20
Q

T/F

Haem is synthesised from Glycine + AcetylCoA

A

False

Glycine + SuccinylCoA

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21
Q

What are the substrates involved in the haem biosynthesis pathway?

A

‘Glycine & SuccinylCoA All Placed high in Urine Cup Produces Protoporphyrin 9’

Glycine + SuccinylCoA
δ Aminolevulinic acid
Porphobilinogen
Hydroxymethylbilane
Uroporphyrinogen (III)
Coproporphyrinogen(s)
Protoporphyrinogen IX
Protoporphyrin IX
(Haem)
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22
Q

T/F

The enzyme deficiency in PCT is Uroporphyrinogen decarboxylase (UROD)

A

True

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23
Q

T/F

The main substrate that builds up in PCT is coproporphyrinogen

A

False

Uroporphyrinogen (III)

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24
Q

What are the enzymes involved in the haem biosynthesis pathway?

A
‘All Sin All hyde, Porphos Uses Urine Cups on Poor Ferrets’ 
Ala Synthase 
Ala Dehydratase 
Porphobilinogen (PBG) deaminase (AIP)
Uroporphyrinogen (III) synthase (CEP)
Uroporphyrinogen decarboxylase(PCT) UROD
Coproporphyrinogen oxidase (HC)
Protoporphyrinogen oxidase (VP0
Ferrochelatase (EPP)
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25
What are the porphyrias and associated enzymes involved in the haem biosynthesis pathway?
Enzymes - (All Sin All hyde,) Porphos Uses Urine Cups on Poor Ferrets’ Porphyrias - All Congenital Porphyrias Have Variable Presentations ``` Porphobilinogen deaminase (AIP) Uroporphyrinogen (III) synthase (CEP) Uroporphyrinogen decarboxylase(PCT) Coproporphyrinogen oxidase (HC) Protoporphyrinogen oxidase (VP0 Ferrochelatase (EPP) ```
26
T/F | The first 2 enzymes in the haem biosynthesis pathway dont cause porphyrias if they are deficient
False Cause rare porphyrias - dont need to know about these ``` Ala Synthase (X-linked dom porphyria) Ala Dehydratase (ALA-dehydratase deficiency porphyria - rare, no skin disease) ```
27
T/F | Urinary porphobilinogen deaminase is raised during acute attacks of porphyria
False Urinary porphobilinogen is raised porphobilinogen deaminase is the deficient enzyme
28
T/F | Acute intermittent porphyria (AIP) is the most rare acute porphyria
False | Most common
29
T/F | Most inherited porphyrias are AR
``` False Most are AD CEP is AR rare cases of EPP are recessive PCT is 75% acquired (type 1), almost 25% AD (type 2) and a tiny proportion types 3 (familial, inheritence unknown) or 'toxic' acquired type due to halogenated aromatic hydrocarbons in herbicides ```
30
What are the high risk factors for developing hepatocellular carcinoma in PCT pts?
male age >50 at presentation symptoms longer >10yrs prior to treatment severe changes on liver bx at presentation Hep C infection
31
T/F | There are two types of PCT
False 2 man types account for the vast majority but there are other; Type I - sporadic acquired Type II - AD Type III - rare familial, inheritence unknown Toxic type Also Hepatoerythropoietic porphyria (HEP) - Pt is homozygous for gene mutation so >90% reduction in UROD - NB mutation diffrent to those seen in type II
32
What are the histo features of PCT (and other bullous porphyrias)?
Cell-poor subepidermal bulla festooning caterpillar bodies in epi PAS +ve, diastase resistant thickening (hyalinization) of upper dermal vessels and BM (reduplication of BM) IMF +ve for IgG +/- IgM, complement + fibringoen at DEJ
33
T/F | CEP is a common mild porphyria
False very rare AR, congenital onset of symptoms mutilating 'warewolf' type severe cutaneous photosensitivity, blistering, erosions, crusts, ulcerations Extensive scarring and deformation of hands Also; Brown stained teeth osteopenia and fractures haemolytic anaemia and splenomegally Hypertransfusion inhibits endogenous haem synthesis but iron overload becomes problematic
34
T/F | >50% of PCT pts have increased total body iron stores
True | 60%
35
T/F | 80% of PCT pt have inherited hameochromatosis
False | 20% in USA and N europe
36
T/F | Homozygous haemochromatosis mutation increases the risk of developing PCT by 20x
False | 60x increase
37
T/F | Iron overload in PCT pts who do not have haemochromatosis is due to excess dietary iron
False | cause unknown
38
T/F | Heterozygous haemochromatosis mutation increases the risk of developing PCT by 20x
False | risk unknown if heterozygous
39
T/F | Hep C infection amongst PCT pts is highest in Southern Europe
True then USA then N Europe
40
T/F | 20% of alcoholics with cirrhosis develop PCT
False | 2%
41
T/F | Alcohol is an important trigger for PCT in susceptible pts
``` True Main triggers are; Subclinical genetic haemochromatosis HepC Acohol Oestrogens (OCP or HRT) ```
42
T/F | Ingested oestrogens are the sole risk factor for PCT in most female pts
False | sole risk factor for PCT in >25% of female pts
43
T/F | 15% of PCTs pts have cirrhosis
True | Must investigate liver
44
What are the causes of Phrynoderma
``` Toad-like skin Vit A, C or E deficiency B-complex deficiency Essential fatty acid deficiency general malnutrition. ```
45
T/F Medications that induce symptoms of Pellagra include: Isoniazid
True | Isoniazid, 5-FU, 6-mercaptopurine, azathioprine, phenytoin, chloramphenicol, sulfonamides, antidepressants.
46
T/F | Medications that induce symptoms of Pellagra include: Systemic 5-fluorouracil
True | Isoniazid, 5-FU, 6-mercaptopurine, azathioprine, phenytoin, chloramphenicol, sulfonamides, antidepressants
47
T/F | Medications that induce symptoms of Pellagra include: 6-Mercapto Purine
True | Isoniazid, 5-FU, 6-mercaptopurine, azathioprine, phenytoin, chloramphenicol, sulfonamides, antidepressants
48
T/F | Medications that induce symptoms of Pellagra include: Sulphonamides
True | Isoniazid, 5-FU, 6-mercaptopurine, azathioprine, phenytoin, chloramphenicol, sulfonamides, antidepressants
49
T/F | Regarding Porphyria's: Photosensitivity is seen in Variegate Porphyria
True
50
T/F | Hypertrichosis is seen in Hepato-Erythropoietic Porphyria
True
51
T/F | Lithium is safe in patients with acute hepatic Porphyria
True
52
T/F | Frusemide is safe in patients with acute hepatic Porphyria
False
53
T/F | 10% of Porphyria Cutanea Tarda patients present in childhood
False | childhood presentation very rare
54
T/F | Regarding dystrophic calcification, it is more commonly associated with adult onset Dermatomyositis over Juvenile
False | Juvenille>adult
55
T/F | Regarding dystrophic calcification, calcification tends to go within the first year of disease onset
False | rarely nodules improve spontaneously after many years in dermatomyositis cases
56
T/F | Regarding dystrophic calcification, the buttocks are frequently affected
True | elbows, knees, shoulders, buttocks
57
T/F | Regarding dystrophic calcification, calcified nodules may improve spontaneously
True | rarely nodules improve spontaneously after many years in dermatomyositis cases
58
T/F | Regarding dystrophic calicification, calcinosis has been described in all clinical subsets of Lupus Erythematosus
True
59
T/F | Coproporphyrins are lipophilic
False uro- and copro-porphyrins are hydrophilic protoporphyrins are lipophilic
60
T/F | In EPP, protoporphyrin accumulates in RBCs mainly
True
61
What tests should be done on blood samples for porphyria?
plasma porphyrins and red cell porphyrin analysis + plasma spectrofluorometry if available
62
T/F | Protoporphyrin accumulates in the red cells in PCT
False red cells are normal in PCT Protoporphyrin accumulates in red cells in EPP
63
Where is the plasma fluorometry peak in PCT?
615-620 nm same for; PCT, CEP and HC
64
T/F | Biochemical findings are the same in HEP as in PCT
False | largely the same but also have red cell zinc-protoporphyrin
65
What are the biochemical findings in PCT?
``` Urine - Uroporphyrin III Feaces - Isocoproporphyrin Red cell porphyrins - normal Plasma porphyrins - Uroporphyrin III Plasma spectrofluorometry peak - 615-620nm ```
66
T/F | plasma and urine porphyrins are increased in renal failure
True | In renal failure it is essential to send faecal sample
67
T/F Faecal sample may be the only way to tell HC and CEP apart as all other prarameters can be the same esp in renal failure pts
True
68
T/F | For porphyria testing, all specimens should be kept at 4 degrees in the dark and analysed within 48hrs
False room temp okay must be kept dark though
69
How does CEP present?
Manifests shortly after birth with severe cutaneous photosensitivity, blistering, erosions, crusts, ulcerations Extensive scarring and deformation of hands Also; - Brown stained teeth - osteopenia and fractures - haemolytic anaemia and splenomegally
70
What are the risk factors for developing PCT?
Subclinical genetic haemochromatosis HepC Alcohol abuse Oestrogens Others – haemodialysis, HIV, T2DM, HepA or B, SLE, dermatomyositis, sideroblastic anaemia, thallasaaemia, haem malignancy, tamoxifen, dialysis - Polychlorinated hydrocarbons (herbicides) (cause toxic type PCT)
71
How does PCT present?
Type I (acquired) presents in middle age whilst Type II (AD) can occur at a younger age
72
What is the link between excess iron in the liver and PCT?
UROD enzyme is inactivated by an inhibitor in the liver. The inhibitor is generated in the liver by reactive oxygen species in presence of iron. The accumulated uroporphyrinogen diffuses from plasma into surrounding tissues, causing a phototoxic reaction in upper dermis of sun-exposed skin. Therefore elevated iron in the liver increases the inhibitor of UROD and results in build up of uroporphyrinogen.
73
``` T/F Hepatoerythropoietic porphyria (HEP) is caused by a mutation in the gene for Coproporphyrinogen oxidase ```
False HEP is due to a homozygous form of familial PCT and associated with over 90% reduction in UROD activity. The mutation in UROD gene is different to that seen in type 2 PCT. Clinically similar to CEP with photosensitivity during infancy and mutilating scarring of face and fingers Coproporphyrinogen oxidase gene is mutated in HC
74
What are the clinical fetaures of PCT?
- Increased photosensitivity and skin fragility Blistering, erosions, crusts, milia, scars in sun-exposed sites Post-inflammatory hyperpigmentation, hypertrichosis, patchy scarring alopecia, morpheaform and sclerodermoid changes
75
T/F | PCT patients are at higher risk of hepatocellular carcinoma as porphyrins are carcinogenic to liver
True
76
T/F | Most patients with genetic Hereditary Coproporphyria get skin involvement
False only 10-20% do Blistering features like PCT presents from puberty onwards
77
T/F | In Variegate Porphyria 80% of pts with mutation are asymptomatic
True
78
T/F | Variegate Porphyria is more common in south america than elsewhere
False | common in south africa
79
T/F | Pts who are homozygous for the AD muattion in VP get severe acute porphyria attacks
False | severe skin disease similar to CEP but do not get acute attacks
80
In VP what proportion of symptomatic pts get skin disease or acute attacks?
Manifests from puberty as skin fragility on backs of hands after sun exposure Of symptomatic pts (only about 20% w/ gene mut); - 70% have cutaneous involvement (same as PCT) - 17% will ever suffer an acute attack
81
How does EPP present?
Manifests in first yr of life Babies crying for no obvious reason Immediate pain, burning, stinging on exposure to bright sunlight of nose, cheeks, dorsal hands within minutes Only clinical sign is subtle oedema of hands during an attack +/- erythema and then wax-like scarring - No blisters unless severe attack Can develop rough pebbly skin over nose, forehead and cheeks thick skin on knuckles and IPJs shallow linear or punctuate scars on cheeks or forehead and radial scars around lips
82
T/F | Protoporphyric or EPP induced liver failure is a rare complication of EPP
True In 1% of EPP cases Protoporphyrins toxic to bile ducts and liver. Need to block theatre lights during liver transplant to prevent severe toxic reaction
83
What is the immediete management of acute attacks of porphyria?
Diagnose by testing urinary PBG level – if normal cannot be acute porphyria Identification and elimination of precipitating factors (porphyrinogenic drugs; alcohol; hormones) Admit to ICU and input from porphyria specialists Careful fluid balance management with correction of hyponatremia Adequate pain therapy, e.g. with opioid analgesics Adequate therapy of nausea and vomiting, e.g. with promethazine, ondansetron + may need anxiolytics IV administration of either: (1) heme arginate or (2) hemin over several days with more extended treatment for severe cases If necessary, until heme preparations become available, intravenous glucose infusions Measurement of urinary porphyrin excretion during the acute attack (daily, if possible) esp porphobilinogen
84
What is the long term management of pts with forms of porphyria prone to acute attacks?
Give a list of ‘safe-drugs’ from Porphyria drug database (e.g. safe antihypertensives to use in a patient with acute porphyrias) NB: even if on safe list not 100% safe in an individual; always check previous reactions if known Abstain from alcohol, cannabis, prolonged calorie-restricted diets Wear emergency identification bracelet (e.g. MediAlert) Screen relatives for clinically latent disease (AD types), genetic counselling (pt if AD, parents if AR) Can reassure patients with PCT, EPP, and CEP that acute attacks are not part of their disease Some pts with frequent uncontrolled acute attacks need liver Tx
85
What is the approach to pts with skin types of porphyria?
Need to: 1) Make diagnosis, 2) Look for triggers & 3) Assess liver disease Ix: urine and red cell porphyrins, plasma porphyrins and plasma fluorometry (or urine + faecal porphyrins) FBC, ELFTs, Iron studies, Hep A/B/C/ HIV serology, HFE gene studies (haemochromatosis), αFP (HCC tumour marker), fasting BSL, ANA, G6PD Liver USS Referral to gastroenterologist for consideration of liver bx Derm Mx 1 Photoprotection, e.g. broad-spectrum PHYSICAL sunscreens and/or protective clothing, window screens for home and car 2 Avoidance of sunlight exposure and trauma 3 For VP or HC can try Oral β-carotene or canthaxanthine PCT and EPP have more specific different treatments
86
What is the specific Rx of PCT?
Venesection - first line: 200–500 ml every 1-4 weeks over ~3–6 months - targets are; keep Hb >100 (100-120) continue until ferritin levels low-normal 20-30 and transferrin sats 15% - This depletes liver iron and allows enzyme function to return to normal Blisters resolve in 3/12, skin fragility in 6-9 & porphyrins normalise in 12 – stop venesection when porphyrin tests normal Venesection is usually 1st line, esp if; - homozygous haemochormatosis mutation (Cys282tyr AKA C282Y) - Or Pathologically high serum ferritin – likely haemochromatosis (most have this) - Or have HepC liver disease requiring iron depletion Measurement of urinary porphyrin excretion to monitor therapeutic outcome Low-dose antimalarials - usually 2nd line option; HCQ 200 mg twice weekly (e.g. on Monday and Thursday) over 6–12 months, until porphyrin excretion is within normal range can use chloroquine at 125-250mg twice per week. Antimalarials form complexes w/ uroporphyrin and increases its excretion in bile Second line therapies: - Desferrioxamine infusions (iron chelating agent) – good for renal failure pts - EPO used to treat ESRF-related PCT or as an adjuvant to venesection when Hb is low but ferritin remains elevated (forces iron into new RBCs) Treatment of Hep C with interferon, ribavirin, telapravir Treatment of HIV with HAART Plasmapheresis/Plasma exchange long term follow up for all pts – venesection induced remission lasts longer – about 2.5yrs, antimalarial remission lasts 1.5-2 years
87
What is the Rx for EPP?
Strict and absolute photoprotection. Avoid sunlight exposure (common window glass does not provide protection) -for acute painful skin – fans, cold water; may need admission for opiates -Oral β-carotene: 30–90 mg/day in children; 60–180 mg/day in adults. Desirable maximum plasma level: 600–800 mcg/dl. Administration during the spring, summer and autumn, with a hiatus during the winter in higher latitudes - nbUVB in spring can reduce severity of attacks -Afamelanotide-α-MSH; 20 mg every 60 days as a resorbable implant) may increase tolerance to light exposure -Consider cholestyramine or charcoal to reduce enterohepatic recirculation of porphyrins and bile acids in order to enhance hepatic porphyrin excretion if pt develops liver problems; results vary -BMT used in rare severe cases esp if liver disease MUST have annual LFTs and red cell protoporphyrin conc to assess for liver failure
88
What is Rx of CEP?
1 Photoprotection, e.g. broad-spectrum sunscreens and/or protective clothing 2 Strict avoidance of sunlight exposure 3 Change day–night rhythm 4 Hypertransfusion to inhibit endogenous haem synthesis 5 Splenectomy (reduces hemolysis and platelet consumption) 6 hematopoietic stem cell transplantation
89
What is Rx of HEP
1 Photoprotection, e.g. broad-spectrum sunscreens and/or protective clothing 2 Strict avoidance of sunlight exposure and trauma 3 Change day–night rhythm 4 Of note, therapeutic approaches used in porphyria cutanea tarda (e.g. phlebotomy, antimalarials) are not effective
90
What are the causes of pseudoporphyria?
Usually due to drugs which cause damage to DEJ by low grade phototoxicity esp in presence of CRF – kind of phototoxic drug eruption esp NODD – Naproxen, OCP, Doxy, Dapsone Naproxen is number 1 cause many other causes Can be induced by regular strong UVA exposure alone e.g. sunbathing with UVB sunscreen only or using IVA sunbed
91
What is pseudoporphyria?
Kind of low grade phototoxicity Closely resemble PCT or VP Most common in CRF Histo the same as PCT Must work up and exclude PCT with biochemical tests Foecal porphyrin analysis differentiates true PCT from pseudoporphyria in renal haemodialysis pts Rx by withdrawing drug and strict sun protection Resolves in weeks usually
92
T/F | Mucin is component of dermal extracellular matrix, and is normally produced in small amounts by fibroblasts
True jelly-like amorphous mixture of acid glycosaminoglycans capable of absorbing 1000 times its own weight in water
93
What are the stains for mucin?
colloidal iron | alcian blue pH2.5
94
T/F | mucin stains with PAS
False
95
What are the types of primary cutaneous mucinosis?
Primary dermal mucinoses and secondary dermal Primary are: Generalised (Diffuse) • Lichen Myxoedematosus (Papular mucinosis) - Generalized (Scleromyxoedema) - Localized = CLANS (as in the local lichen mixed CLANS) Cutaneous (acral) (Papular)mucinosis of infancy Localised (discrete) papular lichen myxoedematosus Acral persistent papular mucinosis Nodular lichen myxoedematosus Self-healing papular mucinosis Juvenile type Adult type - Misc lichen myxoedematosis cases not fitting onto above groups • Reticular erythematous mucinosis (REM) Focal • Focal mucinoses - Cutaneous focal mucinosis - Digital mucous cyst (myxoid cyst)
96
What are the types of secondary cutaneous mucinosis?
``` • Scleredema - Secondary to streptococcal infection - Associated with monoclonal gammopathy - Associated with IDDM • Myxoedema (mucinosis associated with abnormal thyroid function) - Generalized - Localized e.g. pretibial • Follicular mucinosis - Benign types - Lymphoma type • Secondary mucinoses assoc w/ other inflammatory dermatoses, skin cancers or systemic diseases e.g. BCCs, SLE, CutLE, dermatomyositis, Degos disease, CTCL ```
97
T/F | Scleromyxoedema is almost always associated with monoclonal gammopathy IgM
False | almost always associated with IgG monoclonal gammopathy
98
T/F | 50% of scleromyxoedema pts progress to multiple myeloma
False
99
What are the skin changes in scleromyxoedema?
• Numerous, 2-3mm firm waxy closely spaced papules in symmetrical distribution on Head and neck, upper trunk, hands, forearms, and thighs. • Glabella typically involved = leonine facies • Can koebnerise NB No papules seen in scleredema or scleroderma • Often strikingly linear array • Surrounding shiny and indurated skin (i.e. sclerodermoid appearance) + erythema, oedema, brownish discoloration • NB skin is thickened but moveable over subcutis not bound down like in scleroderma • Progression = coalescing of papules to erythematous indurated plaques, skin stiffening, decreased motility of mouth and joints
100
T/F | scleromyxoedema is a rare condition occuring in middle age and affecting men and women equally?
True
101
T/F | scleromyxoedema can be associated with HIV
True | monoclonal gammopathy is most usual but can be HIV
102
What is the doughnut sign in scleromyxoedema?
central depression surrounded by an elevated rim (due to skin thickening) on PIP joints mimics GA
103
What is the salt & pepper sign and who gets it?
hypopigmentation w/ perifollicular retained pigment | seen in systemic sclerosis or scleromyxoedema
104
What are the systemic features of sclermyxoedema?
``` Dysphagia proximal muscle weakness due to myositis peripheral neuropathy (insidious onset in older men) arthropathies carpal tunnel syndrome restrictive or obstructive lung disease scleroderma-like renal disease ```
105
What is the concern when a pt with sclermyxoedema presents with dysarthria and flu-like illness?
Dermato-neuro syndrome: potentially life-threatening encephalopathy; begins abruptly with worsening of skin lesions, flu-like prodrome, fever, seizures, and eventual unexplained coma NB: dysarthria and flu-like illness indicates patient should be promptly admitted to hospital for close observation
106
What are the histological features of the papular mucinoses?
Triad of features: • Diffuse mucin in upper and mid reticular dermis • Increased collagen deposition (fibrosis) • Marked proliferation of irregularly arranged fibroblasts
107
T/F | Lichen myxodematosus is the same as Papular mucinosis
True
108
T/F | Scleromyxedema is the generalised sclerodermoid form of lichen myxodematosus
True
109
What investiagtions are done in ?sclermyxoedema?
``` Diagnosis; - skin Bx Exclude DDs; - TFTs, thyroid Abs - ANA. ENA Asses for triggers; - EPP, BJP, Immunofixation - HIV Assess severity/complications; FBC ELFTs +/- • RFTs • CXR/CT • Urinalysis • EMG • Muscle biopsy ```
110
T/F | 1st line Rx for scleromyxoedeam includes Melphalan chemotherapy, Systemic steroids, IVIg and Plasmapheresis
``` True 1st line • Melphalan chemo - Nit mustard deriv • Systemic steroids - v high dose • IVIg • Plasmapheresis 2nd line • Thalidomide • TCS • ILCS • Isotretinoin • Etretinate • Topical CNI 3rd line • Autologous SCT • UVA1/PUVA • CsA • Cyclophosphamide • MTX • chlorambucil • Electron beam XRT • IFNalpha • ECP • vincristine • Surgery if needed for functional improvemen ```
111
T/F | Localised lichen myxoedematosus is strongly associated with monoclonal gammopathy
``` False localised (diffuse) types have no associations ```
112
T/F | Self-healing cutaneous mucinosis resolves over months to years
False | weeks to months
113
T/F | Reticular erythematous mucinosis (REM) can be hard to distinguish from Jessners lymphocytic infiltrate?
True
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T/F | Reticular erythematous mucinosis (REM) can be hard to distinguish from Discoid lupus?
False | tumid lupus
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What are the clinical features of REM?
F>M, usually middle aged, can be any age inc kids Photodistributed areas of reticular erythema on trunk Pinkish erythema in fine reticular pattern Plaque variant looks ‘sheet-like’ Most often on central chest or mid upper back Infiltrated appearance, areas expand in size
116
T/F | Rarely REM can turn into LE or MF
True
117
What are the associations of Reticular erythematous mucinosis (REM)?
Hyper or hypothyroidism DLE Carcinoma Thrombocytopenic purpura
118
T/F | Reticular erythematous mucinosis (REM) can turn into scleromyxoedema
False
119
T/F | Hydroxyxhloroquine is an effective Rx for Reticular erythematous mucinosis (REM)
``` True HCQ clears in 1-2 months UVA1 2nd line NB steroids dont work should photoprotect ```
120
T/F | Reticular erythematous mucinosis (REM) requires lifelong therapy
False often responds to HCQ Can resolve spontaneously after many years but long term f/u if doesn’t clear as may get MF
121
T/F | Self-healing cutaneous mucinosis mainly affects adults
False | mainly children, rarely adults
122
What are the causes of scleredema?
``` 3 major causes; •Recent (febrile) infection (65-90%) - especially Streptococcal • Diabetes mellitus (‘scleredema diabeticorum’ scleredema of Buschke’) - Obese middle-aged men - Insulin-dependent DM • Monoclonal gammopathy - Usually IgG-kappa or IgA ``` Other infections can trigger scleredema; influenza, measles, mumps, scarlet fever, impetigo, cellulitis, pharyngitis, HIV and other condtions; RA, Sjogren’s, hyperparathyroidism, malignant insulinoma, multiple myeloma
123
T/F | Increased fibroblast numbers are seen in scleredema
False No increased number of fibroblasts (in contrast to scleromyxedema)
124
T/F | In scleredema caused by diabetes controlling hyperglycaemia makes the scleredema improve
False Control of hyperglycemia dose NOT influence skin But in the other types treating the infection or monoclonal gammopathy can improve the skin
125
What are the systemic features of scleredema?
``` Systemic manifestations (in all forms): • Serositis (pleural and pericardial effusions) • Dysarthria and dysphagia • Myositis, parotitis • Ocular (e.g. ophthalmoplegia) • Cardiac (muscle involvement – CCF) • Parotitis ```
126
T/F | scleredema sometimes persists for years?
True post infection type resolves most quickly; months to years Other types often last indefinitely
127
What are the treatments for scleredema?
``` Bath or cream PUVA 1st line UVA1 2nd line nbUVB High dose IV penicillin CsA 5mg/kg ```
128
T/F | Methotrexate is effective in scleredema
False
129
T/F | 50% of follicular mucinosis is associated with lymphoma
False | 0nly 15-30%
130
T/F | alopecia is always present in follicular mucinosis (alopecia mucinosa)
False | not always
131
T/F | A lymphoma in follicular mucinosis is always T cell
False | usually T cell but can be B cell
132
T/F | Lymohoma cases of follicular mucinosis affect a younger age group than benign cases
False • Benign cases present in slightly younger average age group – 2-75 range peak ages 20-40 • Lymphoma type pts can be 20-70, peak age 45
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What are the types of follicular mucinosis?
3 groups – 2 benign and 1 lymphoma-associated; 1. Most cases – solitary or few lesions, develop in wks, clear in 2 months to 2 years 2. Persistant or progressive lesions, lasts years 3. lymphoma associated type – lymphoma present from outset – histo can be subtle though
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T/F | Follicular mucinosis is mainly found on the trunk
False | Mainly scalp, face, neck, shoulders
135
T/F | In follicular mucinosis a monoclonal TCR gene rearrangement indicated lymphoma type
False Is suggestive but not diagnsotic even if monclonal on TCR can still be benign
136
What are the histological findings of follicular mucinosis?
Cystic space forms in outer root sheath and seb gland and mucin accumulates in space Follicle can be destroyed leaving cyst w/ mucin and degenerate root sheath cells Benign forms have many eos lymphoma type has many (atypical) lymphocytes and histo features of MF
137
What is treatemnt ladder for follicular mucinosis?
``` No Rx is an option 1st line • TCS • ILCS • Dapsone • Minocycline 2nd line • PUVA or UVA1 • Indomethacin • Isotretinoin • HCQ • PDT • Superficial XRT • Low dose pred if very itchy • IFN +/- acitretin ```
138
T/F | Macular and lichen amyloidosis are due to AA amyloid
False | Macular and lichen amyloidosis of the skin have altered cytokeratins as the main fibrillar protein
139
T/F | Nodular amyloid of skin or elsewhere has AL fibrillar protein
True
140
How are amyloidoses classified?
``` Can think of Amyloid as Localized - Cutaneous - Primary - Secondary Systemic - Primary - Secondary ```
141
What is amyloid?
Amyloid is a term for a family of biochemically unrelated proteins which may be deposited extracellularly and cause tissue dysfunction • Deposits of amyloid contain one of several fibrillar proteins along with Amyloid P component which prevents proteolysis of the amyloid fibrils, and also associated extracellular matrix components such as GAGs and proteoglycans • Many types of amyloid have ‘AA’ or ‘AL’ proteins as the main fibrillar protein
142
What are the types of Primary (localized) cutaneous amyloidosis (PLCA)?
Macular amyloidosis Lichen amyloidosis (AKA papular amyloidosis) Biphasic (Macular & Lichen/papular together) Nodular Dyschromic
143
What conditions are associated with lichen amyloidosis?
``` Lichen and macular amyloidosis have same associations Genoderms - Mach Likes Pashing 2 Mens Dysko Palms o Pachyonychia congenita o Dyskeratosis congenita o Familial PPKs o MEN 2A Autoimmune o PBC (primary biliary cirrhosis) o Scleroderma o SLE o Dermatomyositis ```
144
T/F | Nodular amyloidosis is associated with SLE and Dermatomyositis
False | Nodular amyloidosis is associated with Sjogren's and diabetes and monclonal gammopathy
145
T/F | Priamry cutaneous amyloidosis is always acquired
False Dyschromic amyloidosis (amyloidosis cutis dyschromia) o Rare congenital variant of primary cutaneous amyloidosis o Characteristic macular and/or papular lesions with a guttate leukoderma on a background of hyperpigmentation on sun exposed skin o May be hypersensitivity to UVB
146
T/F | Macular amyloidosis is most commonly seen in young adult women
True
147
T/F | Macular amyloidosis has a rippled appearance of hyperpigmentation
True
148
T/F | Macular amyloidosis occurs on the back most often and also the chest and buttocks
True
149
T/F | Macular amyloidosis can be pruritic or asymptomatic
True
150
T/F | There is clinical overlap between macular amyloidosis of scapular area and pigmented notalgia paraesthetica in same area
True
151
T/F | Macular amyloidosis is the most common type of priamry cutaneous amyloidosis
False | Lichen amyloidosis is most common
152
T/F | Lichen amyloidosis is always pruritic
True
153
T/F | Lichen amyloidosis occurs unilaterally or symmetrically on extensor surfaces
True Yes starts unilateral then may becomes bilateral and usually on extensors can affect anal or sacral regions esp in oriental men
154
T/F | Nodular amyloid affects women more than men
False M=F but nod amyloid is rare overall macular amyloid affects women more
155
T/F | Nodular amyloid is a type of extramedullary plasmacytoma
True | The AL fibrillar protein is produced by a local abnormal clonal expansion of plasma cells
156
T/F | Nodular amyloid has a 35% risk of having or developing systemic amyloidosis
False | about 7% risk but need long term f/u
157
What are the histo features of nodular amyloidosis?
Diffuse deposition of amyloid in dermis, subcutis and blood vessel walls May be plasma cell infiltrate in perivascular distribution Should do amyloid stains and light chain immunostains
158
T/F | topical steroids are ineffective in treating cutaneous amyloidosis
False Potent TCS under occlusion are first line Can combine with sal acid as keratolytic for lichen amyloidosis Tacrolimus 0.1% ung – good topical 2nd line choice
159
T/F | Physical treatments are of use in cutaneous amyloidosis
``` True o ILCS o UVB o PUVA o Dermabrasion o Ablative CO2 laser o QS KTP laser o PDL NB Acitretin 0.5mg/kg- 1st line systemic but topicals and physical Rx may be better than oral medication ``` ``` • For nodular lesions consider; o Excision +/- graft o Shave or C&C o Cryo o Electrodessication o Ablative CO2 laser; PDL has also been used ```
160
T/F | Primary systemic amyloidosis is most often associated with a plasma cell dyscrazia including myeloma
True
161
T/F | Skin involvement is rare in primary systemic amyloidosis
False | common
162
T/F | Skin involvement is rare in secondary systemic amyloidosis with a chronic inflammatory or infectious disease
True
163
T/F | macroglossia + clubbing is a classic presenting combination in systemic amyloidosis
False | macroglossia + carpal tunnel syndrome
164
Which dermatologic disease can cause secondary systemic amyloidosis?
Psoriasis/ chronic pustular psoriasis Hidradenitis suppuritiva Dystrophic EB
165
Other than dermatologic disease what can cause secondary systemic amyloidosis?
``` RA Ankylosing spondylosis Scleroderma Dermatomyositis SLE Lepromatous leprosy TB ```
166
What are the types of porphyria? which affect skin? which are the 'bullous porphyrias'
‘A Very Hot PEC’ Acute attacks only - Acute intermittent porphyria (AIP) Cutaneous disease and acute attacks - Variegate porphyria (VP) - Hereditary coproporphyria (HC) Cutaneous disease only - Porphyria cutanea tarda (PCT) (+ Hepatoerythropoietic porphyria (HEP): homozygous form of familial PCT) - Erythropoieic protoporphyria (EPP) - Congenital erythropoietic porphyria (CEP) (note this is not the order they arise in when arranged by their enzymes in the haem pathway) All affect skin except AIP - there are some other v rare porphyrias which do not affect skin All cutaneous porphyrias except EPP are bullous porphyrias