Metabolic Dan Flashcards
T/F
Hereditary coproporphyria causes skin disease only
False
Skin + acute attacks
T/F
Porphyria cutanea tarda (PCT) is the most common type of porphyria
True
T/F
Acute intermittent porphyria (AIP) causes acute attacks only
True
no skin disease
AIP is alone in this group
Which porphyrias cause skin disease only?
Porphyria cutanea tarda (PCT)
Congenital erythropoietic porphyria (CEP)
Erythropoieic protoporphyria (EPP)
Which porphyrias cause skin disease and acute attacks?
Hereditary coproporphyria (HC) Variegate porphyria (VP)
T/F
Porphyrias all result from a total deficiency of one of the enzymes required for the biosynthesis of haem
False
from a partial deficiency of one of the enzymes
T/F
‘Bullous porphyrias’ includes all the skin disease causing porphyrias
False
EPP causes pain and erythema on sun exposure not bullae
T/F
All of the porphyrias except AIP cause cutaneous disease
True
T/F
Porphyrins absorb photons of infrared light, with wavelength peak at 408nm
False
visible violet light with peak at 408nm = the Soret band
T/F
Most types of porphyrias are inherited
True
T/F
Most patients with an inherited porphyria get symptoms eventually
False
Most remain asymptomatic
T/F
Accumulation of hydrophobic porphyrins leads to blistering skin disease on light exposure
False
Hydrophilic porphyrins accumulate in skin causing blistering
T/F
Accumulation of lipophilic protoporphyrins leads to an immediate cutaneous burning sensation after exposure to light, accompanied by erythema, and oedema
True
this occurs in EPP
T/F
Variegate porphyria causes immediate cutaneous burning sensation after exposure to light
False
In VP hydrophilic (uro- and copro-) and hydrophobic (proto-) porphyrins accumulate but the blistering skin disease predominates clinically
T/F
Acute porphyria attack is an acute and potentially fatal illness
True
T/F
In liver, a small proportion of available haem is incorporated into cytochrome P450 proteins
False
this is the main fate of haem in the liver
T/F
Acute porphyria attacks are caused by penicillins
False
not one of the main causes but can be true for individuals
What are the triggers of acute attakcs in porphyrias?
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)
What are the features of acute attacks in porphyrias?
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
T/F
Haem is synthesised from Glycine + AcetylCoA
False
Glycine + SuccinylCoA
What are the substrates involved in the haem biosynthesis pathway?
‘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)
T/F
The enzyme deficiency in PCT is Uroporphyrinogen decarboxylase (UROD)
True
T/F
The main substrate that builds up in PCT is coproporphyrinogen
False
Uroporphyrinogen (III)
What are the enzymes involved in the haem biosynthesis pathway?
‘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)
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)
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)
T/F
Urinary porphobilinogen deaminase is raised during acute attacks of porphyria
False
Urinary porphobilinogen is raised
porphobilinogen deaminase is the deficient enzyme
T/F
Acute intermittent porphyria (AIP) is the most rare acute porphyria
False
Most common
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
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
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
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
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
T/F
>50% of PCT pts have increased total body iron stores
True
60%
T/F
80% of PCT pt have inherited hameochromatosis
False
20% in USA and N europe
T/F
Homozygous haemochromatosis mutation increases the risk of developing PCT by 20x
False
60x increase
T/F
Iron overload in PCT pts who do not have haemochromatosis is due to excess dietary iron
False
cause unknown
T/F
Heterozygous haemochromatosis mutation increases the risk of developing PCT by 20x
False
risk unknown if heterozygous
T/F
Hep C infection amongst PCT pts is highest in Southern Europe
True
then USA
then N Europe
T/F
20% of alcoholics with cirrhosis develop PCT
False
2%
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)
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
T/F
15% of PCTs pts have cirrhosis
True
Must investigate liver
What are the causes of Phrynoderma
Toad-like skin Vit A, C or E deficiency B-complex deficiency Essential fatty acid deficiency general malnutrition.
T/F
Medications that induce symptoms of Pellagra include:
Isoniazid
True
Isoniazid, 5-FU, 6-mercaptopurine, azathioprine, phenytoin, chloramphenicol, sulfonamides, antidepressants.
T/F
Medications that induce symptoms of Pellagra include: Systemic 5-fluorouracil
True
Isoniazid, 5-FU, 6-mercaptopurine, azathioprine, phenytoin, chloramphenicol, sulfonamides, antidepressants
T/F
Medications that induce symptoms of Pellagra include: 6-Mercapto Purine
True
Isoniazid, 5-FU, 6-mercaptopurine, azathioprine, phenytoin, chloramphenicol, sulfonamides, antidepressants
T/F
Medications that induce symptoms of Pellagra include: Sulphonamides
True
Isoniazid, 5-FU, 6-mercaptopurine, azathioprine, phenytoin, chloramphenicol, sulfonamides, antidepressants
T/F
Regarding Porphyria’s: Photosensitivity is seen in Variegate Porphyria
True
T/F
Hypertrichosis is seen in Hepato-Erythropoietic Porphyria
True
T/F
Lithium is safe in patients with acute hepatic Porphyria
True
T/F
Frusemide is safe in patients with acute hepatic Porphyria
False
T/F
10% of Porphyria Cutanea Tarda patients present in childhood
False
childhood presentation very rare
T/F
Regarding dystrophic calcification, it is more commonly associated with adult onset Dermatomyositis over Juvenile
False
Juvenille>adult
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
T/F
Regarding dystrophic calcification, the buttocks are frequently affected
True
elbows, knees, shoulders, buttocks
T/F
Regarding dystrophic calcification, calcified nodules may improve spontaneously
True
rarely nodules improve spontaneously after many years in dermatomyositis cases
T/F
Regarding dystrophic calicification, calcinosis has been described in all clinical subsets of Lupus Erythematosus
True
T/F
Coproporphyrins are lipophilic
False
uro- and copro-porphyrins are hydrophilic
protoporphyrins are lipophilic
T/F
In EPP, protoporphyrin accumulates in RBCs mainly
True
What tests should be done on blood samples for porphyria?
plasma porphyrins and red cell porphyrin analysis + plasma spectrofluorometry if available
T/F
Protoporphyrin accumulates in the red cells in PCT
False
red cells are normal in PCT
Protoporphyrin accumulates in red cells in EPP
Where is the plasma fluorometry peak in PCT?
615-620 nm
same for;
PCT, CEP and HC
T/F
Biochemical findings are the same in HEP as in PCT
False
largely the same but also have red cell zinc-protoporphyrin
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
T/F
plasma and urine porphyrins are increased in renal failure
True
In renal failure it is essential to send faecal sample
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
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
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
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)
How does PCT present?
Type I (acquired) presents in middle age whilst Type II (AD) can occur at a younger age
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.
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
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
T/F
PCT patients are at higher risk of hepatocellular carcinoma as porphyrins are carcinogenic to liver
True
T/F
Most patients with genetic Hereditary Coproporphyria get skin involvement
False
only 10-20% do
Blistering features like PCT
presents from puberty onwards
T/F
In Variegate Porphyria 80% of pts with mutation are asymptomatic
True
T/F
Variegate Porphyria is more common in south america than elsewhere
False
common in south africa
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
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
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
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
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
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
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
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
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
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
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
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
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
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
What are the stains for mucin?
colloidal iron
alcian blue pH2.5
T/F
mucin stains with PAS
False
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)
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
T/F
Scleromyxoedema is almost always associated with monoclonal gammopathy IgM
False
almost always associated with IgG monoclonal gammopathy
T/F
50% of scleromyxoedema pts progress to multiple myeloma
False
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
T/F
scleromyxoedema is a rare condition occuring in middle age and affecting men and women equally?
True
T/F
scleromyxoedema can be associated with HIV
True
monoclonal gammopathy is most usual but can be HIV
What is the doughnut sign in scleromyxoedema?
central depression surrounded by an elevated rim (due to skin thickening) on PIP joints mimics GA
What is the salt & pepper sign and who gets it?
hypopigmentation w/ perifollicular retained pigment
seen in systemic sclerosis or scleromyxoedema
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
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
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
T/F
Lichen myxodematosus is the same as Papular mucinosis
True
T/F
Scleromyxedema is the generalised sclerodermoid form of lichen myxodematosus
True
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
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
T/F
Localised lichen myxoedematosus is strongly associated with monoclonal gammopathy
False localised (diffuse) types have no associations
T/F
Self-healing cutaneous mucinosis resolves over months to years
False
weeks to months
T/F
Reticular erythematous mucinosis (REM) can be hard to distinguish from Jessners lymphocytic infiltrate?
True
T/F
Reticular erythematous mucinosis (REM) can be hard to distinguish from Discoid lupus?
False
tumid lupus
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
T/F
Rarely REM can turn into LE or MF
True
What are the associations of Reticular erythematous mucinosis (REM)?
Hyper or hypothyroidism
DLE
Carcinoma
Thrombocytopenic purpura
T/F
Reticular erythematous mucinosis (REM) can turn into scleromyxoedema
False
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
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
T/F
Self-healing cutaneous mucinosis mainly affects adults
False
mainly children, rarely adults
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
T/F
Increased fibroblast numbers are seen in scleredema
False
No increased number of fibroblasts
(in contrast to scleromyxedema)
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
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
T/F
scleredema sometimes persists for years?
True
post infection type resolves most quickly; months to years
Other types often last indefinitely
What are the treatments for scleredema?
Bath or cream PUVA 1st line UVA1 2nd line nbUVB High dose IV penicillin CsA 5mg/kg
T/F
Methotrexate is effective in scleredema
False
T/F
50% of follicular mucinosis is associated with lymphoma
False
0nly 15-30%
T/F
alopecia is always present in follicular mucinosis (alopecia mucinosa)
False
not always
T/F
A lymphoma in follicular mucinosis is always T cell
False
usually T cell but can be B cell
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
What are the types of follicular mucinosis?
3 groups – 2 benign and 1 lymphoma-associated;
- Most cases – solitary or few lesions, develop in wks, clear in 2 months to 2 years
- Persistant or progressive lesions, lasts years
- lymphoma associated type – lymphoma present from outset – histo can be subtle though
T/F
Follicular mucinosis is mainly found on the trunk
False
Mainly scalp, face, neck, shoulders
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
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
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
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
T/F
Nodular amyloid of skin or elsewhere has AL fibrillar protein
True
How are amyloidoses classified?
Can think of Amyloid as Localized - Cutaneous - Primary - Secondary Systemic - Primary - Secondary
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
What are the types of Primary (localized) cutaneous amyloidosis (PLCA)?
Macular amyloidosis
Lichen amyloidosis (AKA papular amyloidosis)
Biphasic (Macular & Lichen/papular together)
Nodular
Dyschromic
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
T/F
Nodular amyloidosis is associated with SLE and Dermatomyositis
False
Nodular amyloidosis is associated with Sjogren’s and diabetes and monclonal gammopathy
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
T/F
Macular amyloidosis is most commonly seen in young adult women
True
T/F
Macular amyloidosis has a rippled appearance of hyperpigmentation
True
T/F
Macular amyloidosis occurs on the back most often and also the chest and buttocks
True
T/F
Macular amyloidosis can be pruritic or asymptomatic
True
T/F
There is clinical overlap between macular amyloidosis of scapular area and pigmented notalgia paraesthetica in same area
True
T/F
Macular amyloidosis is the most common type of priamry cutaneous amyloidosis
False
Lichen amyloidosis is most common
T/F
Lichen amyloidosis is always pruritic
True
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
T/F
Nodular amyloid affects women more than men
False
M=F but nod amyloid is rare overall
macular amyloid affects women more
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
T/F
Nodular amyloid has a 35% risk of having or developing systemic amyloidosis
False
about 7% risk but need long term f/u
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
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
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
T/F
Primary systemic amyloidosis is most often associated with a plasma cell dyscrazia including myeloma
True
T/F
Skin involvement is rare in primary systemic amyloidosis
False
common
T/F
Skin involvement is rare in secondary systemic amyloidosis with a chronic inflammatory or infectious disease
True
T/F
macroglossia + clubbing is a classic presenting combination in systemic amyloidosis
False
macroglossia + carpal tunnel syndrome
Which dermatologic disease can cause secondary systemic amyloidosis?
Psoriasis/ chronic pustular psoriasis
Hidradenitis suppuritiva
Dystrophic EB
Other than dermatologic disease what can cause secondary systemic amyloidosis?
RA Ankylosing spondylosis Scleroderma Dermatomyositis SLE Lepromatous leprosy TB
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
