SLIDE SESSION
Dr Maria
Fabry’s disease
• X-linked lysosomal storage disorder.
• Highly penetrant in males; female heterozygotes have variable
expressivity.
• Partial or complete deficiency of alpha-galactosidase A with
deposition of glycosphingolipids (mostly globotriaosylceramide).
• Neutral sphingolipids with terminal -galactosyl residues
(predominantly globotriaosylceramide [Gb3]) accumulate in the
lysosomes of different tissues and fluids (epithelial cells of
glomeruli and tubules of the kidneys; cardiac myocytes; ganglion
cells of the autonomic system; cornea; endothelial, perithelial, and
smooth muscle cells of blood vessels; and histiocytic and reticular
cells of connective tissue
Cutaneous findings
• Angiokeratomas
• Angiomas
• Telangiectasias
• Lymphedema
• Hypohidrosis/ hyperhidrosis
• Raynaud’s phenomenon
• Pseudoacromegalic facies
Non cutaneous Findings
• Ocular
• Cornea verticillata
• Renal
• Chronic renal failure • Conjunctival vessel aneurysms
• Cardiovascular • Increased tortuosity of retinal vessels
• Hypertension • Fabry cataract
• Coronary vascular disease • GI
• Left ventricle hypertrophy • Diarrhea
• Valve disease • Nausea
• Arrhythmias • Vomiting
• Elevated high-density lipoprotein • Postprandial ank pain
• Neurologic/psychiatric • Malabsorption
• Acroparesthesias • Others
• Cerebrovascular disease • Hearing loss and tinnitus
• Dementia • Hypothyroidism
• Depression • Obstructive airway disease
• Increased suicide ideation • Osteopenia and osteoporosis
HISTOPATHOLOGY
• Dilated, ectatic capillaries in the papillary dermis,
a variably thinned epidermiscentrally, with
epidermal acanthosis at the edges of the lesion,
and variable degrees of overlying focal compact
orthohyperkeratosis
• Endothelial, perithelial, perineural, eccrine,
smooth muscle cells, and fibroblasts are filled
with cytoplasmic vacuoles containing
glycosphingolipid that can be visualized with
toluidine blue stains.
• Electron-dense, lamellated, intracytoplasmic
vacuolar inclusions (Zebra bodies) are typically
seen on electron microscopy
Differential Diagnosis of
Angiokeratomas
ANGIOKERATOMA
LOCALIZED FORMS CORPORIS DIFFUSUM
• Angiokeratoma of Fordyce • Fucosidosis
• Angiokeratoma of the vulva • Aspartylglycosaminuria
• Angiokeratoma of Mibelli • Galactosialidosis
• Solitary papular • Schindler/Kanzaki disease
angiokeratoma • Beta Mannosidosis
• Angiokeratoma • GM-galactosidase
circumscriptum - • Sialidosis
• Idiopathic
Differential diagnosis
• Chloroquine therapy
• Tuberous sclerosis, juvenile dermatomyositis,
also associated with widespread
angiokeratomas
Prognosis
• Life expectancy shortened by 20 years in
males and 15 years in females
TREATMENT
• Symptomatic • Hyperhidrosis
• Angiokeratomas • Aluminium chloride hexahydrate
• Liquid nitrogen • Electrophoresis
• Electrocoagulation • Botulinum toxin
• Surgical excision • Glycopyrrolate sodium
• Laser (pulsed-dye 585 nm, • Raynaud phenomenon
neodynium YAG [Nd:YAG] 1064 nm, • Avoid smoking, cold and
• combined pulsed-dye and Nd:YAG) vasoconstrictor therapies
and intense pulsed light • Losartan
• Lymphedema • Diltiazem
• Manual lymphatic drainage massage • Fluoxetine
and compression • Sildenal
Treatment
• Pain • Cardiovascular
• Avoid triggers • Antihypertensive drugs
• Diphenylhydantoin • Antiarrhythmia drugs
• Carbamazepine • Articial pacemakers
• Gabapentin • Implantable debrillators
• Stroke • Coronary bypass
• Chronic renal failure
• Antiplatelet
• Angiotensin converting enzyme
• Anticoagulant inhibitors
• Hearing • Hemodialysis
• Hearing aid devices • Allograft transplant
• Avoid noise trauma • -Galactosidase B (Fabrazyme)
• Lungs • -Galactosidase A (Replagal)
• Avoid smoking • Migalastat (for patients with amenable
mutations
• Bronchodilators
• GI
• Pancrelipase
• Metoclopramide
DIFFERENTIAL DIAGNOSIS
• GRANULOMA ANNULARE
• Tinea corporis
• Subacute cutaneous lupus erythematosus
• Annular lichen planus
• Actinic granuloma/annular elastolytic giant cell
granuloma
Granuloma annulare
• It is a disease of the skin and subcutaneous tissue
characterized by granulomatous annular plaques, nodules or
papules containing foci of altered collagen surrounded by
histiocytes and lymphocytes
GRANULOMA ANNULARE
• Granuloma annulare is most common in children and young
adults but can occur at any age
• It is twice as common in women as in men
ASSOCIATIONS
• The prevalence of diabetes is probably not increased amongst
patients with GA
• Autoimmune thyroiditis, uveitis, hyperlipidaemia, temporal
arteritis, morphoea, necrobiosis lipoidica and sarcoidosis
have also been reported
• HLA‐Bw35
VARIANTS OF GA
• Localized
• Generalized,
• Subcutaneous
• Perforating.
GA represents a reaction pattern to a variety of triggering factors
• Infections and infestations • Sunlight exposure
• Scabies , • Drug‐induced GA
• hepatitis B , • tumour necrosis factor α (TNF‐α)
• Mycobacterium tuberculosis , blockers
• human papillomavirus , • Erythema multiforme
• varicella/zoster , Epstein–Barr virus
, parvovirus B19 , hepatitis C , HIV
and
• Borrelia burgdorferi
• Traumatic triggers
• immunizations , tuberculin testing
• animal and insect bites ,
• waxing and saphenectomy
• Perforating GA has also been
reported in the red areas of tattoos
Pathology
• The most characteristic histological lesion in GA is the
necrobiotic granuloma, but there are three histological
patterns that mayoccur:
• (i) necrobiotic palisading granulomas;
• (ii) interstitial form; and
• (iii) granulomas of sarcoidal or tuberculoid type
Complications and co‐morbidities
• Anetoderma
• Mid‐dermal elastolysis
Disease course and prognosis
• 50% of patients the lesions resolve within 2
years. However, about 40% recurrence occurs
in the majority of cases at the same sites
Treatment ladder
First line
• No treatment/expectant
• Cryotherapy
• Intralesional corticosteroid
• Potent topical corticosteroid
Second line
• Topical tacrolimus
• Pimecrolimus
• Imiquimod
• Narrow‐band UVB phototherapy
• PUVA
• Dapsone
• Ciclosporin
• Fumaric acid esters
• Methotrexate
Third line
• Photodynamic therapy
• Laser
Multiple large crateriform nodules with central keratinous contents
on the back of a patient with hypothyroidism
Differential Diagnosis
• Acquired perforating disorder
• Actinic granuloma (annular elastolytic giant cell granuloma
• Lichen planus
• Multiple keratoacanthomas (Ferguson-Smith familial
keratoacanthomas,
• Perforating granuloma annulare
• Perforating periumbilical calcic elastosis
• Perforating pseudoxanthoma elasticum
• Porokeratosis
• Prurigo nodularis
• Psoriasis
• Sarcoidosis
• Scabies
Acquired perforating disorders
• Acquired perforating disorders represent a
group of separately identifed cutaneous
disorders that occur most often in the setting
of chronic renal disease or diabetes mellitus.
Acquired perforating disorders
• KYRLE DISEASE/
• ACQUIRED PERFORATING COLLAGENOSIS
• PERFORATING FOLLICULITIS
• ACQUIRED ELASTOSIS PERFORANS
SERPIGINOSA
Conditions Associated with Acquired
Perforating Dermatosis
• Common Associations
• Chronic kidney disease
• Diabetes mellitus (insulin-dependent and noninsulin-dependent)
• Scabies
• Rare Associations
• AIDS
• Arthropod bites
• Atopic dermatitis
• Cutaneous cytomegalovirus infection
• Hyperparathyroidism
• Liver diseases
• Lupus vulgaris
• Myelodysplastic syndrome
• Malignancy
• Mikulicz disease
• Neurodermatitis
• Poland syndrome
• Primary sclerosing cholangitis
• Pulmonary aspergillosis
• Pulmonary brosis
• Salt water application
• Thyroid disease
• Vitamin A deciency
HISTOPATHOLOGY
• Histopathologic examination of lesional skin
demonstrates invagination of the epidermis
with extrusion of dermal material (collagen,
elastin, and/or fibrin) through the cup-shaped
epidermal depression.
PROGNOSIS
• APD may improve with successful treatment
of the underlying illness. Most cases of APD
continue for years unless treated.
• Topical Therapies
• Retinoic acid
• Tretinoin
• Tazarotene
• Beclomethasone Corticosteroid
• Triamcinolone acetonide
• Corticosteroid 10 mg/mL intralesional injection
• Imiquimod
• Phenol
• Capsaicin
• Systemic Therapies
• Isotretinoin
• Acitretin
• Prednisolone
• Allopurinol
• Doxycycline
• Metronidazole
• Clindamycin
• Hydroxychloroquine
• Physical modalities
• UVB
• NUVB
• PUVA
• Liquid nitrogen
• CO2 LASER
• Surgical debridement
THANKS
