Sarcoidosis

Presenter : Sanjay Singh

Introduction

Sarcoidosis is a multisystem disorder of unknown origin, characterized by the accumulation of noncaseating epithelioid granulomas

Also known as Boeck’s disease and “Mortimer’s malady “

Sarcoidosis is presently considered a great dermatologic masquerader and its incidence is on increase

History of Sarcoidosis

Earliest description of sarcoid given by Besnier in 1889 – described as Lupus Pernio

Tenneson gave first histopathological description in 1892

Boeck introduced term “Sarcoid” in 1899 and concept that disease involves both skin and internal organs

In Greek sarco means “flesh,” eidos means “like,” and osis means “condition” - sarcoidosis means a flesh like condition

Epidemiology Sarcoidosis affects all races, both sexes, and all ages

Peaks between the ages of 25 and 35 years; a second peak occurs in women aged 45 to 65 years

Sex ratio, M:F :: 1.5:1

US : 10 - 40 cases per 1 lakh

Scandinavia : 50-60 cases/1 lakh

African Americans have more severe and rapidly progressive disease course

Chronic skin lesions are also more common in African Americans

INDIAN SCENARIO

True burden of sarcoidosis in India is not clearly known

Due to high prevalence of TB in India and also resemblance in clinicoradiological features

All ethnic groups in Indian sub-continent are affected by sarcoidosis

M > F

Majority of them present in their 4th or 5th decade of life

• Cutaneous involvement occurs in about 11 to 34 percent of patients with sarcoidosis

Sarcoidosis in India: Not so rare. Sharma SK, Mohan A. JIACM 2004;5:12–21.

Etiopathogenesis

Etiopathogenesis of sarcoidosis is not completely known

Granulomatous disease caused by hyperactivity of CD4 +T cells

Induced by exposure to infectious agent or environmental substance in genetically

predisposed individuals

Etiologic agents proposed to be associated with sarcoidosis

Environmental and occupational Infectious Mildew

Mold

Insecticides

Combustible wood

Firefighting

Building materials

Industrial organic dusts

Mycobacteria

Propionibacterium acnes

Viruses (herpes, Coxsackie B, CMV, retrovirus, and Epstein-Barr, HHV-8, Hepatitis-C)

Borrelia burgdorferi

Mycoplasma

Chlamydia

Yersinia

Genetic predisposition • Familial clustering is reported in sarcoidosis (10% probability in sibling )

Consistent Human Leukocyte Antigen Associations

HLA Allele Association

B8 Susceptibility

DQB1*0201 Protection, good prognosis, Lofgren’s syndrome

DRB1*0301 Acute onset, good prognosis, Lofgren’s syndrome

DRB1*04 Protection

DRB1*1101 Susceptibility in Caucasians and African Americans

DRB3*0101 Susceptibility, disease progression in Caucasians

Genetic predisposition

Angiotensin Converting Enzyme (ACE) gene polymorphism might play a role

Presence of GLU residue at position 69 of HLA-DPB1 is also implicated

Expression of the acute phase reactant genes ORM1 (orosomucoid) and HP1

(haptoglobin) is also increased in sarcoidosis

Clinical Features

CUTANEOUS DISEASE

Based on Histopathology

Specific Non-specific

Specific FormsFrequent Types Less frequent Types Specific locationPapular Maculopapular PlaqueAnnularLupus pernioSubcutaneous nodulesScar

AngiolupoidHypopigmentedLichenoidUlcerative AtrophicPsoriasiformVerrucousNecrobiosis lipoidica-like lesionsIchthyosiformErythrodermicMorpheaformPolymorphousPhotodistributedTumoral

Oral cavityScalp NailGenital

Papular sarcoidosis

• Often present on face, especially around the eyelids and nasolabial folds

• Presents with numerous nonscaly skin-coloured, yellow-brown, red-brown, violaceous or Hypopigmented 1 to 10 mm papules

• Coalescence of lesions may lead to formation of annular or non-annular plaques

• Associated with favourable disease prognosis, and lesions usually resolve without significant scarring

• Sometimes, upon resolution, faintly discolored, occasionally atrophic macules develops

(i) Multiple dusky red papules over cheeck, nasal and chin area (ii) Over upper back

Papular sarcoidosis of the knees

Recently described

Papules in linear array

Considered a transitional form between papular and scar sarcoidosis

Associated with Erythema nodosum

Good prognosis

Maculopapular Sarcoidosis

• Most commonly involves neck, trunk, extremities and mucous membranes

• Commonly associated with acute organ involvement

• Sometimes transient and appear to herald onset of disease

• Sign of good prognosis, in most cases systemic disease is inactive within <2 years

Plaque Sarcoidosis• Plaque sarcoidosis have a similar frequency to papules

• More commonly develops on back, buttocks, face, and extensor surfaces of extremities

• Consist of one or multiple round or oval infiltrated patches, brownish red in colour, and may be due to a confluence of papules

• Larger than 5 mm in diameter and tend to be thicker and more indurated than papules

Lesions are persistent

Commonly associated with chronic forms of sarcoidosis

Plaques tend to recur and on resolution frequently leave permanent scarring

Plaque Sarcoidosis Over lower back

Annular sarcoidosis

Circinate or annular papules and/or plaques predominate mainly on forehead, face and neck

Central area may become depigmented and scarred

Ulceration is rare

Lupus pernio

Most characteristic cutaneous lesion of sarcoidosis

Hallmark of chronic fibrotic disease

More commonly seen in black women and west indian with long standing sarcoidosis

Chronic, violaceous to telangiectatic, induration, predominantly on nose and cheeks

Lesions enlarge and become confluent to form progressively disfiguring nodular plaques on

nose and adjacent cheeks

Can involve upper respiratory tract and cause nasal ulceration, obstruction, and perforation

of nasal septum

Rarely involve dorsal hands, finger and toes, and lytic and cystic lesions in underlying bones

Commonly coexists with other cutaneous involvement, particularly with plaques

Perthes Jungling disease

• Lytic and cystic bone lesions in hands and feet underlying lesions of lupus pernio

• When terminal phalanx is affected the nail may be dystrophic

• Drumstick dactylitis : A severe form with bulbous swelling of fingertips

Perthes Jungling disease : Osteolysis of Distal Phalanyx (index finger)

Lupus pernio usually follows a very chronic course

Frequent association with systemic involvement

Mutilating sarcoidosis

Severe form of lupus pernio

Large centrofacial tumors/plaques extending into oral and upper respiratory tissue

(i) Lupus Pernio (nodular type) (ii) Mutilating lesion with extension in nasal muosa

Subcutaneous sarcoidosis

Also known as Darier-Roussy sarcoidosis

Appears as non-tender, firm, mobile, subcutaneous nodules 0.5–2cm in diameter

1 to 100 in number, sometimes appearing in clusters, and arise deep in the dermis

and subcutaneous tissue of extremities and trunk

More common on forearms, where they tend to coalesce to form linear band

Lower extremity : Differentiated from erythema nodosum by absence of tenderness and inflammation

Often associated with stage I on chest radiograph, along with other non-severe systemic findings of disease

Multiple Skin coloured nodules in linear array over forearm

Scar sarcoidosis

Characterized by infiltration of noncaseating sarcoidal granulomas in surgical scars, tattoos, skin

piercings, and other sites of trauma

Difficult to clinically distinguish from a granulomatous foreign body reaction in a scar

Tends to persist according to activity of systemic sarcoidosis, and usually resolves slowly and

spontaneously

New scar infiltration in patients with sarcoidosis in remission suggests a reactivation of disease

Old scars should always be examined when sarcoidosis is suspected

Controversial reports have suggested an increased incidence of systemic involvement

while others have reported isolated cutaneous disease

Angiolupoid sarcoidosis

Variant of plaque sarcoidosis characterized by the presence of prominent large telangiectasias

Lesions are orange-red or reddish-brown in colour and have a more livid hue than other forms

Usually presents as a single raised plaque on the bridge of the nose, central face, ears or scalp

Little tendency to spontaneous resolution

Easily mistaken for rosacea

Erythematous to violaceous plaque over nose with prominent telangiectesia

Hypopigmented sarcoidosis

• Affects almost exclusively dark-skinned persons of African descent

• Lesions manifest as hypopigmented, well demarcated, round to oval patches located mainly on extremities

• Fried egg appearance : Erythematous papules can be found in the centre of some lesions, leading to an appearance resembling a fried egg

• Histopathology : Interface dermatitis

Hypopigmented macules over extremities with central erythematous plaque (fried egg appearance

Lichenoid sarcoidosis

Multiple 1 to 3 mm, erythematous or violaceous, slightly scaling maculopapules involving an extensive area of the skin

Occur singly or in groups, especially localized on the trunk, limbs, and face

Wickham striae are absent

Lichenoid lesions have been particularly reported in young children

Specific triad of skin, joint, and eye disease

Pulmonary disease is not usually found

Infiltrated, nonfollicular, lichenoid papules over knee Dermoscopy : Absence of white Wickham striae

Dermoscopy for discriminating between lichenoid sarcoidosis and lichen planus

Vazquez-Lopez F, Palacios-Garcia L, Gomez-Diez S, et al. Arch Dermatol. 2011;147(9):1130.

Ulcerative Sarcoidosis

• Generally develop in papulonodular lesions, some appear de novo

• Ulcer can develop in psoriasiform, atrophic, lymphedematous, erythrodermic and verrucous lesions

• Located primarily on lower legs and tend to heal with scarring

• Trauma can be inciting factor in other sarcoidosis lesions

Ulcerative Sarcoidosis Venous ulcer

Edema - +

Hyperpigmentation in surrounding skin

- +

Granuloma + -

Ulcerative sarcoidosis. Case report and review of the literatureAlbertini JG, Tyler W, Miller OF. Arch Dermatol 1997;133(2):215-9.

• Total no. of Cases : 35

• Leg ulcer was present in 29 patients

• 11 patients presented with ulcers as initial sign of sarcoidosis

• Various cutaneous sarcoid lesions were presenting complaint in 15 others

• Ulcers generally developed in papulonodular lesions

Clinical Feature No. of Cases

Respiratory symptoms 12

Ocular disease 9

Splenomegaly 8

Hepatomegaly 7

Lymphadenopathy 7

Bone cysts 6

Arthropathy 2

Psoriasiform sarcoidosis

• Presents with well-demarcated, erythematous, scaly plaques that may be clinically indistinguishable from psoriasis

• Involves extensor surface of extremities, face, scalp, back, and buttocks

• Multiple configurations, including discrete, confluent, annular, and polycyclic, have been reported

Sarcoidosis and psoriasis: a case series and review of the literature exploring co-incidence vs coincidence

Wanat KA, Schaffer A, Richardson V et al. JAMA Dermatol 2013;149(7):848-52.

• 7 patients with both sarcoidosis and psoriasis vulgaris

• 3 patients had cutaneous sarcoidosis, and one had evidence of both psoriasis and sarcoidosis in same cutaneous specimen

• Similar pathogenesis of TH1 and TH17 in both sarcoidosis and psoriasis suggest that a common pathway may exist and that association may be more than coincidental.

Verrucous sarcoidosis

• Most commonly seen on face or areas such as the groin and axillae where there is constant friction

• Well demarcated, exophytic, hyperkeratotic plaques or discrete papillomatous, skin-coloured papules

Necrobiosis lipoidica-like lesions

• Pink to violaceous plaques with depressed centres located on shins

Ichthyosiform sarcoidosis

• Adherent, irregular, polyclonal, dry, grey or brown scales varying in size from 0.1cm to 1cm

• Most commonly located on lower extremities

• Biopsy : Typical sarcoidal granulomatous inflammation with changes of ichthyosis vulgaris

Erythrodermic sarcoidosis

• Presence of large areas of skin with significant erythema, induration and scaling

• Typically begins with slightly infiltrated, erythematous to yellow-brown plaques that subsequently coalesce over large areas

• Skip areas can be seen

Morpheaform Sarcoidosis

Indurated and atrophic plaques indistinguishable from morphea

Predominantly located on the thighs of black woman

Histopathology : Epithelioid granulomas along with dermal sclerosis is observed

Polymorphous sarcoidosis

• Presence of different types of lesions, both specific and nonspecific, in same patient

• Usually associated with multisystem disease

Photodistributed sarcoidosis

• Rare form of sunlight-induced papular sarcoidosis with negative phototesting

Sarcoidosis of oral cavity

Usually consist of diffuse enlargement at submucous level or a firm, nodular lesion,

with normal overlying mucosa

Papules, superficial ulcerations and strawberry gums have also been described

Usually symptomless

Most commonly seen on buccal mucosa, followed by gums, lips, floor of mouth,

tongue and palate

(i) Nontender, indurated mass in the right buccal submucosa with overlying intact mucosa (ii) Erythematous infiltrated gingiva

Scalp alopecia

Usually scarring alopecia

Less commonly nonscarring alopecia

Scale is usually absent, although follicular plugging can be seen

Late stage : Indistinguishable from pseudopelade of Brocq

Nail sarcoidosis

Present as subungual hyperkeratosis, clubbing, pitting, trachyonychia, paronychia with nail fold fissuring, pterygium, onycholysis, dactylitis, longitudinal ridging, and discoloration of nail bed

Nail involvement is usually a marker of chronic disease

Often accompanied by phalangeal bone disease, which is frequently associated with intrathoracic sarcoidosis

Non specific cutaneous manifestations

Symmetric, tender, erythematous nodules and raised plaques

Present on anterior aspect of lower extremity

Most common non-specific lesion, develops in up to 25% of sarcoidosis cases

Good prognostic significance (self resolving nature of disease)

Erythema nodosum

Lofgren Syndrome

> 80% cases resolve spontaneously within 2 years

HLA-DRB1 alleles affect disease prognosis in Lofgren syndrome

Erythema

nodosum

Acute Polyarthri

tis

B/L Bronchohilar Lymphadenopat

hy

Other Non specific cutaneous manifestations

Calcinosis cutis

Erythematous rash resembling viral exanthem or drug reaction

Pruritus and prurigo nodularis

EM like lesions

Lower limb swelling

Childhood sarcoidosis

• Uncommon in children

• Affects both sexes equally

• Early onset <5 year and late onset ≥ 5 year

• Classic presentation is with triad of arthritis, erythema nodosum, and uveitis in <5 year group

• Older children usually present with a multisystem disease similar to adult manifestations, with frequent hilar LAD and pulmonary infiltrations

Most frequent cutaneous eruptions include soft, red to yellowish brown, or violaceous, flat-topped papules, found most frequently on face

If no skin lesions then lymph nodes are best for biopsy

Spontaneous resolution more common

Specific cutaneous lesions in patients with systemic sarcoidosis: relationship to severity and chronicity of disease

Marcoval J, Mañá J, Rubio M. Clin Exp Dermatol 2011;36(7):739-44.

• Total Patients : 86 pts of systemic sarcoidosis with follow up of > 2 years

• Cutaneous lesions developed before or at time of diagnosis of systemic sarcoidosis in 80.23% of patients

• Plaque : 31 • Maculopapules : 28• Subcutaneous : 14• Scar : 7• Lupus pernio : 6• Erythema nodosum : 30

Plaques and LP were associated with persistence of systemic sarcoidosis and requirement for systemic corticosteroids

Maculopapules and subcutaneous sarcoidosis are usually associated with EN and radiological stage I, and indicate good prognosis

Cutaneous involvement in sarcoidosis: analysis of the features in 170 patientsYanardağ H, Pamuk ON, Karayel T. Respir Med 2003;97(8):978-82.

• Total no. of patients : 516

• Cutaneous involvement : 170 (32.9%)

n % Parenchymal involvement, n %

Erythema nodosum 106 (20.5) 11 (10.4)

Skin plaques 22 (4.3) 4 (18.2)

Subcutaneous nodules 22 (4.3) 4 (18.2)

Maculopapular rash 19 (3.7) 2 (10.5)

Scar lesions 15 (2.9) 6 (40)

Lupus pernio 14 (2.7) 9 (64.3)Psoriasiform lesions 5 (0.9) -

Good Prognosis Poor Prognosis No prognostic significance

Papular sarcoidosis Plaque sarcoidosis Scar sarcoidosis

Maculopapular Lupus pernio

Subcutaneous sarcoidosis Angiolupoid sarcoidosis

Childhood sarcoidosis Ichthyosiform sarcoidosis

Erythema Nodosum Verrucous sarcoidosis

Lofgren syndrome Hypopigmented

Lichenoid Sarcoidosis Nail sarcoidosisScalp sarcoidosisSarcoidal alopecia

Polymorphous sarcoidosis

Ulcerative sarcoidosis

Systemic manifestations

Lung manifestations (90%)

• B/L hilar lymphadenopathy

• Granulomas involve interstitial areas, bronchioles, alveoli and blood vessels

• Primary alveolitis

• Irreversible fibrosis

• Pleural effusions

• Presents with dyspnea, cough and rarely hemoptysis

Stage I & II

Normal X-ray Stage I Stage II

Stage III

Normal X-ray Stage III

Stage IV

Normal X-ray Stage IV

Upper respiratory tract lesions ( 5% to 20% )

• Can present as lupus pernio

• Granulomatous invasion of nasal and oral mucosa, larynx and pharynx, salivary glands

(sarcoidal ranula), tonsil and tongue

• Enlargement of parotid gland : 6% of patients

• Presents with nasal congestion, palatal obstruction and disfigurement

Ocular manifestations (30% to 50%)

Gritty sensation

Conjunctivitis sicca

Acute anterior uveitis

Iris nodules

Scleral plaques

Lacrimal gland enlargement

Chorioretinitis

Musculoskeletal involvement (30 - 40% )

Manifestations include weakness, pain, tenderness, and erythema

Bone cysts and osteolytic Lesions

Chronic myopathy

Muscle nodules

Arthralgias, arthritis, fever, weight loss

Tenosynovitis

Investigations

Histopathology

• Histopathologic hallmark : superficial and deep dermal epithelioid cell granulomas devoid of prominent infiltrates of lymphocytes or plasma cells (“naked tubercles”)

• Central caseation is usually absent

• Fibrinoid deposition may be observed in up to 10% of cases

• Multinucleated histiocytes (“giant cells”) are usually of Langhans type, with nuclei arranged in a peripheral arc or circular fashion

• Asteroid bodies : Stellate eosinophilic inclusions made up of complex lipids

• Schaumann (conchoidal) bodies : round or oval inclusions consisting of laminated calcium oxalate; these may represent residual bodies of lysosomes

• Crystalline inclusions : Colorless, round or oval, refractile, nonlaminated inclusion bodies composed of calcium oxalate that may represent precursors of Schaumann bodies

• Neither finding is specific for sarcoidosis

4X

10X

Asteroid bodies Schaumann bodies

Granulomas containing strands of staining reticulin

Feature Sarcoidosis TuberculosisGeneral Monomorphic Caseating

Tubercles Discrete, naked Diffuse, confluent

Epithelioid cells Large, grouped Irregular or at margin of caseation, less than 50%

Giant cells Large and sparse Small and numerous

Inclusion bodies Frequent Occasional

Vessels Normal or dilated Fibrinoid changes

Reticulin Fine and abundant destroyed

Fibrinoid necrosis centre In vessels

Healing Hyalinization from periphery Dense collagen mesh, retraction and calcifications

Ancillary diagnostic tests

• Cutaneous anergy ≈ 90%

• Kviem-Siltzbach test (90% with hilar adenopathy)

SACE – serum angiotensin levels

• Only an adjunctive investigation

• Not diagnostic, not prognostic, not useful for monitoring

• Because of false-positive rate of 10% and a false-negative rate of 40%

Increased Serum ACE Levels

Leprosy

Alcoholic liver disease (cirrhosis),

α1-antitrypsin deficiency

Diabetes mellitus

Kaposi’s sarcoma/HIV

Melkersson-Rosenthal syndrome

Histoplasmosis

Asbestosis

Silicosis

• Gallium - 67 scan

• Bronchoalveolar lavage

• 24 hour urine calcium

Anergy to tuberculin in sarcoidosis is not influenced by high prevalence of tuberculin sensitivity in the population

Gupta D, Chetty M, Kumar N et al. Sarcoidosis Vasc Diffuse Lung Dis 2003;20(1):40-5.

Group IN = 50

Group IIN = 62

Control = 130

Tuberculin AnergyN = 46 (92%)

1 TU tuberculin

Tuberculin AnergyN = 55 (88.7%)

Control : 21 (16.2%)

1 TU tuberculin

Tuberculin AnergyN = 39 (70.9%)

Tuberculin AnergyControl : 6 (28.6%)

5 TU tuberculin

Assessment for systemic sarcoidosisRecommended basic assessment for sarcoidosis in patients presenting with specific

(granulomatous) cutaneous lesions

History (including occupational and environmental exposures)

Physical examination

Ophthalmological examination (slit lamp and ophthalmoscopic examination)

Chest radiograph

Standard haematological and biochemistry profiles (including urine and serum calcium level, liver and renal function tests), and serum angiotensin-converting enzyme (SACE) level

Electrocardiogram

Pulmonary function tests (including spirometry and diffusion of carbon monoxide)

Tuberculin skin test

Treatment

• Sarcoidosis is a self limiting disease 60% of patients with spontaneous resolution in 6-18 months

Topical therapy

• High-potency topical corticosteroids

• Intralesional triamcinolone injections

• Tacrolimus

• Cryotherapy and radiotherapy

• PUVA therapy has been successful in hypopigmented sarcoidosis and in Erythrodermic sarcoidosis

• In certain types of cutaneous sarcoidosis, for example lupus pernio, cosmetic camouflage is helpful

Indications for Systemic Treatment

1. Symptomatic pulmonary disease

2. Progressive or persistent parenchymal lung disease after 2 years

3. Posterior ocular disease or anterior disease not responding to local steroids

4. Persistent fever or weight loss

5. Liver disease with significant dysfunction or hepatosplenomegaly

6. Disfiguring skin disease or lymphadenopathy

7. Nervous system disease

8. Hypercalcaemia

9. myocardial disease

10. myopathy or myositis

11. Thrombocytopenia

12. other significant organ involvement—for example, kidneys

Sarcoidosis. Johns CJ, Scott PP, Schonfled SA. Ann Rev Med 1989; 40: 353–

71.

American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders.

Criteria for considering corticosteroid treatment in sarcoidosis

• Progressive symptomatic pulmonary disease

• Asymptomatic pulmonary disease with persistent infiltrates or progressive loss of lung function

• Cardiac disease

• Neurological disease

• Eye disease not responding to topical therapy

• Symptomatic hypercalcaemia

• Other symptomatic/progressive extrapulmonary disease

Summary of pharmacologic agents used for treatment of cutaneous sarcoidosis

Treatment Usual dose Indications Level of evidence

Class I ultrapotenttopical corticosteroids

0.05% ointment applied twice weekly or under occlusive dressing

Limited and discrete papules and plaques

IIB

I/L triamcinolone 3-10 mg/mL every 3-4 wks until resolution occurs

Limited & discrete papules, plaques, and nodules

IIB

Oral corticosteroid Initially, 0.5-1 mg/kg/d (prednisone equivalent); gradually taper to lowest effective dose (often 10 mg/d) and switch to an every other day schedule

1. Widespread, disfiguring, chronic lesions

2. Lesions refractory to local therapy

3. Recalcitrant LP4. Ulcerative lesions

IIB

Chloroquine 250-750 mg daily; maximum dose is3.5 mg/kg/d

Steroid-sparing agent or as monotherapy is effective in all lesionsVery effective for LP

IIB

Hydroxychloroquine 200-400 mg daily; maximum dose is6.5 mg/kg/d

Same as for chloroquine IIB

Methotrexate 7.5-25 mg/wk orally, SQ or IM; maintenance dose may be administered biweekly

Steroid-resistant lesionsor patients unable to take steroids; especially useful for ulcerative sarcoidosis

IIB

Tetracycline Minocycline, 200 mg/dTetracycline, 1,000 mg/d

Helpful in selected cases IIB

Thalidomide 50-400 mg/d Refractory skin disease,especially LP

IIB

Infliximab 3-7 mg/kg IV at 0, 2, and 6 wks (3-10 mg/kg) and then every 6 wks

Widespread disease, severely disfiguring lesions, and refractory lesions

IIB

Adalimumab 40 mg every 1-2 wks Widespread disease, severely disfiguringlesions, and refractory lesions

III

Algorithm for treatment

Specific skin lesions

Cosmetically insignificant or asymptomaticCosmetically significant or symptomatic

No treatment indicated

Limited, mild to moderate disease Widespread, severe disfigurement or Lupus Pernio

Topical or I/L corticosteroids

Systemic Corticosteroids&

Steroid Sparing AgentSteroid sparing agent :Anti-malarials

OrMethotrexate

OrMMF

Slowly taper medicationTNF-α antagonist

Slowly taper systemic corticosteroidsMaintain adjuvant therapy

Anti-malarialsOr

MethotrexateOr

Tetracycline

Try alternativeAnti-malarials

OrMethotrexate

OrTetracycline

Systemic Corticosteroids

Slowly taper systemic corticosteroids maintain

steroid-sparing

Experimental therapyOr

Laser AblationOr

Surgery

No improvement

No improvement

No improvementClinical response

No improvement

Systemic steroids contraindicated

Clinical response

Clinical response

No improvement