Kevin Svancara DO PGY3 Jennifer Peterson DO PGY3Advanced Desert DermatologyMidwestern University AZCOM

http://www.aocd.org/?page=GranulomaAnnulare

Benign Asymptomatic Self-limited granulomatous disease of the dermis Five common Variations

- Localized- Generalized- Subcutaneous- Perforating- Patch

http://www.aocd.org/?page=GranulomaAnnulare

Etiology/Pathogenesis- Unknown Thought to be a delayed type hypersensitivity reaction TH-1 Response causing degradation of collagen May be induced by

▪ trauma▪ sun exposure▪ TB skin testing▪ vaccinations▪ viral infections▪ herpes zoster▪ genetic predisposition - HLA-B35 has had increased frequency in two studies

Classic variant Skin colored, pink non scaly papules

coalescing into annular or arciform plaques, moderately firm, ropelike border with central clearing. Most common locations on the distal extremities

http://www.aocd.org/?page=GranulomaAnnulare

Generalized 15% of cases 10 or more lesions 45% have lipid abnormalities More chronic and relapsing course

Subcutaneous Most common form in children Scalp and extremities Painless

http://drcamisasblog.com/2013/11/17/granuloma-annulare-5/

http://dermnetnz.org/dermal-infiltrative/granuloma-annulare.html

Rare variants include –Perforating, Patch Histology

Palisading Granuloma with a necrobiotic foci in the dermis

Mucin present

lymphocytic infiltrate

http://www.dermpedia.org/case-type/9?page=65

Associated Disorders Diabetes Mellitus

The relationship between diabetes and GA is controversial Earlier studies presented a relationship, more recent studies

have failed to find the association previously reported Autoimmune Thyroiditis Hodgkin's and Non Hodgkin's Lymphoma Hyperlipidemia and Hypercholesterolemia HIV Hep B and C

Treatments Often self-limited – 50% resolve within the first 2 years

First Line – High potency topical or intralesional steroids

Destructive▪ Cryotherapy: 25/31 patients had resolution with 1 treatment (10-60

sec)

▪ Biopsy – controversial

Lasers – PDL, CO2, Excimer

Treatments Oral antibiotics

▪ Doxycycline 100mg bid▪ Dapsone

Antimalarials▪ Hydroxychloroquine, Chloroquine

Immunosuppressants▪ Methotrexate, Cyclosporine, TNF-a

Light Therapy▪ NBUVB, PUVA, PDT

Take home points Benign – self limited in 50% of cases

Delayed type hypersensitivity reaction – TH-1

Localized form – most common

Subcutaneous form – most common in children

Can be associated with autoimmune thyroiditis

Consider checking triglycerides in generalized GA

http://www.dermis.net/dermisroot/en/37834/image.htm

Clinical DM associated –65% of patient’s have DM. Only

found in 0.3% of DM patients

average age of 25 in patients with DM

Non-DM associated in mid 40s

Most commonly located on the anterior shins.

Red, brown or violaceous papules. Progress to yellow, brown, atrophic telangiectatic plaques.

Pathogenesis

Exact etiology remains unknown.

One theory suggests that NL results from systemic microangiopathy associated with DM.

May precede diabetes

http://www.dermis.net/dermisroot/en/37834/image.htm

Pathology

Histology – Layers of granuloma in between pale degenerated collagen. Plasma cells, no mucin

Treatment First Line – High potency (Class I) topical steroids under

occlusion

Intralesional steroids – Use caution not to cause ulceration

Topical PUVA

Antimalarials – Hydroxychloroquine 200mg qd

Fumaric Acid Esters – Not approved by the FDA

Pentoxifylline

Take home points

Only a small portion of patients with DMII (0.3%) will develop Necrobiosis Lipoidica

Histology: Palisading Granuloma

without mucin

Located on anterior shins

http://www.dermis.net/dermisroot/en/37834/image.htm

http://www.aocd.org/resource/resmgr/ddb_high/sarcoidosis_2_high.jpg

http://www.aocd.org/?page=Sarcoidosis

Clinical - can affect multiple organs: Lungs most common Skin manifestations occur in 17% of patients Cutaneous manifestations are the initial presentations in 1/3

of patients Multiple presentations exist Macules, papules, nodules and plaques

▪ red-brown, yellow-brown, violaceous, or hypopigmented

Erythema nodosum – most commonnon-specific cutaneousmanifestation

http://escholarship.org/uc/item/3sh1s1qd/1b.jpg

Pathogenesis - Unknown Thought to involve genetically influenced

dysregulation of the Th-1 immune response to one or more extrinsic antigens

May lead to over activation of inflammatory pathways and subsequent granuloma formation

Case control study of 700 patients was unable to find any single etiologic agent.

Histopathology Non-caseating granulomas

Aggregates of epithelioid histiocytes

Giant cells

Macrophages

Minimal lymphocytic

infiltratehttp://dermaamin.com/site/histopathology-of-the-skin/71-s/2091-sarcoidosis-.html

Histology

Schaumann bodies

▪ Basophilic laminated

Inclusions in giant cells

Asteroid Bodies

▪ Eosinophilic stellate inclusion bodies

https://upload.wikimedia.org/wikipedia/commons/7/7b/Sarcoidosis_-_Schaumann_body_2.jpg

http://www.pathologyoutlines.com/wick/sarcoid%20lymph%20node%20micro%20asteroid%20body.jpg

Variants Lupus Pernio – violaceous infiltration of the nose,

cheeks or earlobes, often

associated with a chronic

course▪ Can cause scarring after resolution

▪ Often associated with upper

respiratory tract disease

http://www.dermis.net/bilder/CD183/550px/img0053.jpg

Lofgren’s Syndrome

Triad

▪ Erythema nodosum - Most common non-specific cutaneous finding, 25% of patients with sarcoidosis

▪ bilateral hilar adenopathy

▪ migrating polyarthritis

https://escholarship.org/uc/item/8rg7v60g/lofgren2.jpeg

http://www.hindawi.com/journals/crirh/2013/125251.fig.001.jpg

Heerfordt’s syndrome –Uveoparotid fever

Fever

parotid gland enlargement

anterior uveitis

facial nerve palsy

http://development.aao.org/publications/eyenet/200805/images/AMRdroop400.jpg

Darier-Roussy disease - Sarcoidal panniculitis

painless subcutaneous mobile nodules without epidermal change.

http://escholarship.org/uc/item/90z93266/032007_1a.jpg

Treatment – lack of high quality evidence to support efficacy

Topicals - super potent steroids, mid potency for face.

Intralesional injections systemic corticosteroids for severe disease

20-40mg/kg/day with a slow taper May add hydroxychloroquine 200-400mg/day or

methotrexate 25mg/week, tapered to 5-15mg

minocycline – retrospective study of 27 patients, 14 had partial improvement while 6 had complete improvement on 1-6 months of minocycline

Refractory treatments Biologics - TNF – alphas – notably infliximab but

data has been conflicting in larger studies

Take home points

Lesions that develop within a scar or tattoo should be ruled out for sarcoidosis

Erythema Nodosum – positive prognosis, associated with acute sarcoidosis

TH1 response to unknown antigen

https://www.dermquest.com/imagelibrary/large/044989HB.JPG

http://dermaamin.com/site/images/clinical-pic/m/macular-amyloidosis/macular-amyloidosis2.jpg

Cutaneous Macular Lichen Nodular Secondary

Systemic Primary systemic Secondary systemic Hemodialysis- associated

Macular

Keratinocyte derived

Hyperpigmented firm papules localized to the interscapular region

▪ Asymptomatic or pruritic

▪ Commonly associated with notalgia paresthetica

http://dermaamin.com/site/images/clinical-pic/m/macular-amyloidosis/macular-amyloidosis2.jpg

Lichen amyloidosis

Keratinocyte derived

Flat topped shiny papules

Commonly over the shins

Pruritic

Seen in MEN 2A

http://dermaamin.com/site/images/clinical-pic/L/lichen-amyloidosis/lichen-amyloidosis10.jpg

Nodular Single or multiple waxy nodules

▪ occasionally with purpura

AL –immunoglobin light chains▪ Frequently Lambda light chains

Long term follow up needed for potential to progress to systemic

Systemic Primary Systemic

▪ Pinch Purpura - ecchymosis and vessel fragility ▪ Macroglossia – indentation of teeth▪ Shoulder pad sign- deposition

around periarticular soft tissue▪ AL -light chain▪ May be associated with multiple

myeloma https://stanfordhealthcare.org/content/dam/SHC/conditions/blood-heart-circulation/images/alprimaryamyloidosis-photo-tongue.jpg

Hemodialysis associated amyloidosis Long term hemodialysis Beta 2 microglobulin Deposition in synovial membranes

▪ Carpal Tunnel Senile Systemic amyloidosis

Late onset in elderly patients ATTR - Transthyretin

Treatment Macular

▪ Capsaicin▪ Topical steroids

Lichen▪ Topical and intralesional steroids▪ NBUVB▪ CO2 laser▪ Retinoids

Nodular▪ Excision or laser ablation

Clinical – Symmetricwaxy firm papules, leoninefacies, commonly involves the glabella with longitudinal

furrowing Pathology

Associated with monoclonal gammopathy (debatable) IgG lambda light chain

Treatment –IVIG, Bortezomib, melphalan, thalidomide, stem cell transplant

http://www.atsu.edu/postgrad/dermatology/ppt/mucin2006_files/slide0010_image030.jpg

http://images.rheumatology.org/image_dir/album75672/md_04-10-0056.jpg

Clinical - Cutaneous brawny induration of the face, neck, scalp and upper extremities

Three forms Infection related – Streptococcal Gammopathy related – Monoclonal gammopathy, IgG

Kappa Diabetes – IDDM

Treatment – Phototherapy, cyclophosphamide, oral glucocorticoid, cyclosporine

http://images.rheumatology.org/image_dir/album75672/md_04-10-0056.jpg

http://www.dartmouth.edu/~thabif/weeklyclinic111901/pictures/19porphyriacthands.jpg

Blisters, erosions and milia on sun exposed skin

Most common type of porphyria world wide

http://www.dartmouth.edu/~thabif/weeklyclinic111901/pictures/19porphyriacthands.jpg

Defect – Uroporphyrinogen Decarboxylase

Triggers Alcohol HCV Estrogen Iron Over load Hemochromatosis

Labs: Total plasma porphyrins with reflex Then stool, plasma and RBC fractionation

Treatment - Phlebotomy every 2 weeks, may combine with antimalarials

Hydroxychloroquine: 100mg BIW

Takes on average 6.5 months to reach therapeutic levels with hydroxychloroquine and phlebotomy

Better compliance than phlebotomy

http://dermaamin.com/site/images/clinical-pic/e/erythropoietic_protoporphyria/erythropoietic_protoporphyria5.jpg

Most common porphyria in children Clinical – erythema, edema, crust, purpura and

skin thickening Labs – Total erythrocyte protoporphyrin

Urine porphyrin levels normal Complications

Protoporphyric hepatopathy Gallstones

http://dermaamin.com/site/images/clinical-pic/e/erythropoietic_protoporphyria/erythropoietic_protoporphyria5.jpg

Treatment Broad Spectrum Sunscreen, Photo protective

Clothing

Avoidance of sunlight exposure from 11:00 AM –3:00PM

Beta-Carotene 30-90mg/day in children

Cysteine supplements, 500mg bid

Afamelanotide

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melanocyte stimulating hormone. Photochem Photobiol. 2009 Nov;85(6):1434-9. 14. Mathews-Roth MM, Rosner B, Benfell K, et al. A double-blind study of cysteine photoprotection in erythropoietic protoporphyria. Photodermatol Photoimmunol Photomed. 1994 Dec;10(6):244-8. 15. Jain, S. 2012. Dermatology:Illustrated Study Guide and Comprehensive Review. New York, NY: Springer. 16. Sanchez M, Haimovic A, Prystowsky S. Sarcoidosis. Dermatol Clin. 2015; 33(3): 389-416. 17. Ladizinski B, Lee KC. Lichen Amyloidosis. CMAJ. 2014; 186(7): 532.