Cutaneous Mucinoses Flashcards
Special stains for mucin
Alcian blue pH 2.5
Colloidal iron
Toluidine blue pH 4.0
What is associated with a Scleromyxoedema
Monoclonal gammopathy (immunoglobulin G lambda) No thyroid disease
What is the microscopic triad of scleromyxoedema
Diffuse Mucin deposition (confirmed with a mucin stain)
Fibroblast proliferation (irregularly arranged fibroblasts)
Fibrosis @ increased collagen deposition
Clinical features of scleromyxoedema
Widespread eruption 2-3mm firm waxy closely spaced dome-shaped/flat topped papules - can be itchy
Arranged linear pattern
Surrounding skin sclerodermoid (shiny and thick)
Leonine facies (deep furrowing forehead)
Shar-pei sign (deep furrowing trunk, shoulder, limbs)
Sparse eyebrow, axillary, pubic hair
Doughnut sign over PIP joints
Sclerodactyly
Rarely Raynaud’s phenomenon
Lacks telengiectasia/calcinosis (scleroderma features)
No mucosal lesions
DDx of scleromyxoedema and differences with scleromyxoedema
Scleroderma/systemic sclerosis (no papules, positive ANA, anticentromere, antiScl70)
Sclerodema (no papules, assoc URTI, diabetes)
Nephrogenic systemic fibrosis (no facial involvement/monoclonal gammopathy, renal dysfunction + exposure to gadolinium)
Systemic involvement of scleromyxoedema
Haem - 100% monoclonal gammopathy, rarely others I.e. myeloma, lymphoma etc
Neuro - carpal tunnel syndrome, peripheral neuropathy, memory loss, stroke, seizures, psychosis, gait issues, vertigo, dermatoneuro syndrome)
Rheum - Arthralgias/arthritis, myopathy, myalgia
Cardiovascular - CCF, myocardial ischaemia, heart block
Pulmonary - obstructive or restrictive
GI - dysphagia
Renal - acute RF
Prognosis of scleromyxoedema
Chronic, progressive, unpredictable course
Causes of death in scleromyxoedema
Dermatoneuro syndrome (concomitant fever, convulsions, coma)
Cardiovascular
Haem malignancies
Baseline investigations for scleromyxoedema
Skin biopsy
Serum and urine protein electrophoresis with immunofixation
TFT normal
Little value in imaging
Treatment ladder for scleromyxoedema
1st line -
IVIg 2g/kg for 5 days alone or in combo with Lenalidomide/systemic steroids - skin and extra cutaneous, esp for acute deterioration with neuro symptoms, response not permanent, maintenance infusions required every 6-8 weeks
2nd line (combined with IVIg rather than as mono therapy) - Lenalidomide 100-400mg/day +/- Systemic steroids
3rd line -
Autologous peripheral blood stem cell transplant
Bortezomib and dexamethesone (for recurrences and dermatoneuro syndrome)
Additional treatment for scleromyxoedema
Medical - Oral retinoids Cyclosporin Interferon alpha Hydroxychloroquine
Chemo -
Melphalan
Cyclophosphamide
MTX
Physical - Plasmapheresis PUVA, UVA1 Electron beam Extracorporeal photochemo
Cutaneous mucinoses classification
PRIMARY MUCINOSES Dermal - lichen myxoedematosus (scleromyxoedema, localised lichen myxoedematosus) - reticular erythematous mucinosis - scleroedema - myxoedema in thyroid diseases (pretibial myxoedema) - papular and nodular mucinosis in CTD - self healing cutaneous mucinosis - cutaneous focal mucinosis - digital myxoid cyst
Follicular
- Pinkus follicular mucinosis
- Urticaria-like mucinosis
SECONDARY MUCINOSES
Localised lichen myxoedematosus clinical features
Small firm waxy papules, nodules, plaques confined to few sites No sclerotic features No paraproteinaemia No systemic involvement No association with thyroid disease 4 subtypes - acral persistent papular mucinosis - papular mucinosis of infancy - discrete papular lichen myxoedematosus - nodular lichen myxoedematosus
4 subtypes of localised lichen myxoedematosus
Acral persistent papular mucinosis
Papular mucinosis of infancy
Discrete papular lichen myxoedematosus
Nodular lichen myxoedematosus
Localised lichen myxoedematosus pathology
Mucin in the upper and mid reticular dermis
Variable fibroblast proliferation
Fibrosis not marked/absent
Grenz zone (acral persistent papular mucinosis)
Acral persistent papular mucinosis (subtype of localised lichen myxoedematosus)
Multiple ivory to skin coloured papules
Exclusive on dorsal hands, distal forearms
Discrete papular lichen myxoedematosus (subtype of localised lichen myxoedematosus)
Small reddish, violaceous or skin coloured papules
Trunk and limbs
Symmetrical distribution
Papular mucinosis of infancy (subtype of localised lichen myxoedematosus)
Firm opalescent papules
Neck
Trunk
Upper arms
Nodular lichen myxoedematosus (subtype of localised lichen myxoedematosus)
Multiple nodules
Mild/absent papular component
Trunk, limbs
Localised lichen myxoedematosus associations
HIV
Hep C
Exposure to toxic oil/L-tryptophan
DDx of localised lichen myxoedematosus
Granuloma annulare
Lichen amyloidosus
Lichen planus
Eruptive collagenoma
Disease course of localised lichen myxoedematosus
Chronic but benign course, in the absence of systemic involvement
Prognosis for localised lichen myxoedematosus
Progression to scleromyxoedema has never been proven
Reticular erythematous mucinosis (REM) clinical features
Chronic persistent macular erythema, indurated erythematous papules/plaques Reticular configuration Lack of scale Midline back, chest Occasionally itchy Sometimes face, abdomen, arms, legs
Reticular erythematous mucinosis (REM) associations
Generally not related to systemic diseases
Not associated with abnormal lab tests
Malignancies - haem, breast, lung, colon HIV Thyroid dysfunction Diabetes Idiopathic thrombocytopenic Purpura SLE
Reticular erythematous mucinosis (REM) aggravating factors
OCP Pregnancy Menses Heat, sweat X-ray therapy Role of sunlight is controversial
Family Hx
Reticular erythematous mucinosis (REM) pathology
Epidermis normal
Mucin in upper dermis
Slight vascular dilatation
Perivascular (sometimes perifollicular) T cell infiltrate, with variable deep extension
DIF negative (rarely IgM, IgA, C3 at DEJ)
DDx for reticular erythematous mucinosis (REM)
Tumid lupus - clinical and histo similarities, lack immune serological abnormalities, respond well to HCQ, resolve without residual lesions (tumid lupus without reticulated lesions on the midline are strongly photosensitive, higher positive DIF, higher recurrence rate, present with other lupus features)
Seb derm - central chest, scale
Pityriasis versicolor - central chest, scale
Confluent and reticulated papillomatosis of Gougerot-Carteaud (CARP) - scale
Disease course of reticular erythematous mucinosis (REM)
Chronic
Prolonged duration of untreated
May clear spontaneously
Treatment ladder for reticular erythematous mucinosis (REM)
First line
HCQ 400mg daily - improvement/healing within 1-2 months
Second line
TCS
Systemic steroid
Topical calcineurin inhibitors I.e. tacrolimus, pimecrolimus
Third line
Phototherapy I.e. UVA1, UVB (potential for exacerbation, but successful results reported)
PDL
Other
Oral antihistamines
Tetracycline
CSA
Scleroedema clinical features
Non-pitting swelling/induration
Upper part of body (neck, shoulders, upper back) - typically begin on posterior neck, spread to scalp, shoulders, upper back
Spares hands and feet
Erythema
Peau d’orange appearance
Symmetrical, diffuse
Progressive
Limited body mobility/movement restriction
Subtypes
- Diabetic
- Non diabetic (idiopathic, with preceding febrile illness/post-strep, with monoclonal gammopathy/multiple myeloma, misc conditions I.e. HIV, internal malignancy, autoimmune disorder)
Subtypes of scleroedema
Diabetic (poorly controlled insulin-dependent) - slowly progressive, non-resolving
Non diabetic
- idiopathic
- with preceding febrile illness/post-strep URTI (also influenza, measles, mumps, chickenpox, CMV, diphtheria, encephalitis, dental abscess) - acute onset, complete resolution 6 months-2 years
- with monoclonal gammopathy/multiple myeloma - slowly progressive, non-resolving
- misc conditions I.e. HIV, internal malignancy, autoimmune disorder (RA, primary biliary cirrhosis, sjogren syndrome, dermatomyositis)
Scleroedema path
Normal epidermis
Thickened dermis
Swollen collagen fibres separated by wide spaces
Mucin
Subcut fat replaced by coarse collagen fibres
No fibroblast proliferation
DDx of scleroedema
Systemic sclerosis (has additional sclerodactyly, Raynaud phenomenon, nail fold capillary changes, positive serum autoantibodies) Dermatomyositis Other infiltrates - - Myxoedema (mucin) - Amyloidosis (amyloid) Lymphoedema Cellulitis
Extracutaenous complications of scleroedema
Serositis Myositis Parotitis Hepatosplenomegaly Ocular Cardiac Dysphasia Dysarthria
Scleroedema course/prognosis
Post-infectious scleroedema - benign course, self-limiting, resolves spontaneously 6 months - 2 years
Diabetes/monoclonal gammopathy associated scleroedema - chronic, little chance of remission
Initial investigations for scleroedema
To detect underlying disorder
Throat swab, ASOT - recent strep infection
Fasting blood glucose, HBA1C - diabetic control
Serum, urine protein electrophoresis and immunofixation - monoclonal gammopathy, multiple myeloma
USS - evaluate skin thickness at baseline, after treatment
MRI - extent of disease progression (better than USS for this purpose)
Treatment of scleroedema
Difficult, limited success
No effective treatment
Some patients (but not all) diabetes patients improve with better glucose control
First line -
Treat underlying cause
UVA1, PUVA, nb-UVB (for disabling manifestations)
Physio MSK rehab (for motion/respiratory disability)
Second line -
Electron beam radiotherapy
Extracorporeal photopheresis
IVIg
Third line (immunosuppressants) -
CSA
MTX
TCS, ILCS, pred
Pretibial myxoedema clinical features
Bilateral shins, dorsum feet
Thickened and indurated skin
Orange peel appearance/texture due to prominent hair follicles
Overlying hyperhidrosis or hypertrichosis
4 variants -
- diffuse non-pitting oedema
- plaque type
- nodular type
- elephantiasis
Hyperthyroidism esp Graves’ disease, sometimes Hashimoto’s thyroiditis
Sometimes no past/present Hx of thyroid dysfunction
Pretibial myxoedema path
Hyperkeratosis Papillomatosis Acanthosis Follicular plugging Mid to lower dermis separation of collagen bundles by mucin Perivascular lymphocytic infiltrate Increase mast cells Normal/increased fibroblasts Reduced elastic fibres
DDx for pretibial myxoedema
LSC
Hypertrophic lichen planus
Obesity-associated lymphoedematous mucinosis (no thyroid disease)
Pretibial myxoedema course/prognosis
Elephantiasis variant less likely to have remission
Entrapment of peroneal nerve by mucinous connective tissue —> foot drop, faulty dorsiflexion
Initial investigations for pretibial myxoedema
Biopsy
Anti-TSH antibodies - high
TSH - low —> high thyroid hormone to stimulate more TSH production
Treatment of pretibial myxoedema
General measures -
Reduce weight
Stop smoking
Normalise thyroid function (though pretibial myxoedema can still develop after treatment started)
First line -
Medium to high potency TCS under occlusion
ILCS
Compression stockings/gradient pneumatic compression (improves lymphoedema)
Second/third line (only for elephantiasis variant) - Rituximab Extracorporeal plasmapheresis IVIg Octreotide \+/- shave removal N.B relapse after skin graft
Papular and nodular mucinosis in connective tissue diseases features
Skin coloured papules, nodules, plaques
Trunk, upper extremities
Accompany/antedate connective tissue disease I.e. LE (cutaneous lupus mucinosis, usually associated with SLE but may also be associated with DLE/SCLE), dermatomyositis, scleroderma
Clinical course may/may not be related to the underlying connective tissue disease activity
Path - abundant mucin throughout dermis, sometimes subcut fat, slight/moderate perivascular lymphocytic infiltrate, positive lupus band
General measures - sunscreen
First line treatment - TCS, ILCS, HCQ
Resistant cases - Pred, oral tacrolimus
Self-healing juvenile cutaneous mucinosis
13 months - 15 years old
Acute eruption of multiple papules, sometimes linear infiltrated plaques scalp, face, neck, abdomen, thighs
Subcut nodules face, periarticular areas on limbs, periorbital swelling
Systemic symptoms - fevers, arthralgias, weakness, muscle tenderness
No paraproteinaemia/bone marrow plasmocytosis/thyroid dysfunction
Spontaneous resolution few weeks - months
Avoid aggressive therapy as heals spontaneously
Cutaneous focal mucinosis
Benign localised cutaneous dermal mucinosis
No systemic manifestations
Anecdotal associations - hypothyroidism, myxoedema, scleromyxoedema, REM, anti-TNF Rx
Reactive lesion
Trauma may act as a trigger
Asymptomatic solitary skin coloured papule/nodule, sometimes with cystic appearance
Anywhere except in proximity of the joints of the hands, wrists, feet
Treatment - surgical excision
Path -
- Diffuse ill-defined dermal mucin
- Spares subcut tissue
- Normal/slight increase fibroblast (spindle-shaped cells)
- No inflammation
- No increased vascularity
- No elastic fibres
- Normal/hyperplastic epidermis, sometimes forming collarette
DDx - angiomyxoma (benign >1cm, subcut involvement by mucin + increased vascularity)
Digital myxoid cyst
Benign ganglion cyst of digits
Translucent dome shaped soft/fluctuate nodule
+/- visible semi transparent contents
Dorsal skin/near distal interphalangeal joint
Surface smooth or verrucous
Clinical/radio graphic evidence of osteoarthritis
Grooving of the nail may precede/associate the cyst by up to 6 months
Antecedent trauma in minority of cases
MRI can denote Connection of cyst to underlying joint
2 variants -
Over joints - ganglion type derived from joint fluid and synovial cells
Between interphalangeal joints - myxomatous type derived from dermal fibroblasts
Histo -
Large deposit mucin containing stellate fibroblasts
Multiple clefts
Vascular spaces
Epidermis - atrophied centrally, acanthotic laterally
Sometimes transepidermal elimination of mucin
Treatment -
No consistently successful treatment
Excision (relapse not uncommon)
Multiple needling/aspiration followed by ILCS/cryo/sclerosant/CO2 laser (favoured as a conservative alternative to excision)
Pinkus follicular mucinosis
Children, adults in 30s/40s
Familial cases ? Genetic predisposition
Acute/subacute eruption
1 or several sharply demarcated erythematous plaques with follicular prominence (more reassuring if solitary lesion on the head/neck)
Alopecia
Scaling
Differentiation with MF-associated follicular mucinosis is difficult
Histo -
Mucin within follicular epithelium, sebaceous glands abusing keratinocytes to disconnect from each other
Perifollicular infiltrate of lymphocytes, histiocytes, eosinophils
Absence of epidermotropism/atypical lymphocytes (favour MF-associated follicular mucinosis)
T cell gene rearrangement not always useful to exclude MF-associated follicular mucinosis
Treatment-
No specific Rx
Consider wait and see - many cases heal spontaneously 2-24 months
Topicals - TCS, topical calcineurin inhibitor, topical retinoids/bexarotene, imiquimod
ILCS
Systemic - Pred, isotretinoin, minocycline, dapsone, HCQ, interferon alpha-2b
Physical - PDT, UVA1
Urticaria-like follicular mucinosis
Cyclic eruption of itchy urticaria-like papules/plaques
Head/face/neck of middle-aged men
Rosaceiform/seborrhoeic background skin
Red macules persist for a few weeks as lesions resolve
No follicular plugging
No alopecia
No systemic manifestations
DDx - Urticaria Seb derm Rosacea Tumid lupus
Histo -
Mucin deposition within hair follicles
Perivascular and perifollicular infiltrate of lymphocytes and eosinophils
T-cell gene rearrangement polyclonal
Treatment -
Chronic
Difficult to treat
Systemic - HCQ, Dapsone
