clinical seminar 13 jluy 2009

8/8/2019 Clinical Seminar 13 Jluy 2009

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To acquire knowledge, one must study;To acquire knowledge, one must study;

butbut

To acquire wisdom, one must observeTo acquire wisdom, one must observe

Marilyn vos SavantMarilyn vos Savant


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Clinical SeminarClinical Seminar

withwith

Thomas RuengerThomas Ruenger

Muhammad Khawar NazirMuhammad Khawar Nazir

0707--1313--20092009


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ChiefComplaintChiefComplaint

Painful red bumps on both lower legs and feetPainful red bumps on both lower legs and feetsince last several monthssince last several months


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Picture 1/5Picture 1/5


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Physical Examination

Lower extremities: left knee mildly swollen,no erythema, noincreased temp, tender to deep palpation. Mildly positive

patella tap. Twopustules of each knee 3 mm in diameter.Multiple non blanchable red macules, papules, hemorrhagic

vesicles some with crusting and others eroded of the lower 1/2of legs.

Posterior right leg: erythematous plaque with central incisonfrom prior I&D. , healing

Feet: multiple non blanching red - violaceous macules,papules, hemorrhagic vesicles and few pustules on dorsum offeet, toes and lateral soles of feet.


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DifferentialDifferential

DiagnosisDiagnosis

??


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StoryStory

41 year old female, follow up visit on 07ollow up visit on 07--0606--2009, last visit on 062009, last visit on 06--2525--20092009

Followed up for a painful red, eroding and crusting eruption of the legs and feet,several months.

History ofChrons disease since years, was on Remicad till Decmeber 2007

Started on Humira in December 2007but was not consisitent with weeklyinjections due to tonsillitis treated with prednisone.

April 08, on resuming Humira more consistently she notice that she had aneruption of her feet that herPCP thought was eczema which waxed and wanedwith doses of prednisone.

May 08 she had a similar eruption in the same area of her feet.

June 09 when she was off prednisone and on Humira, she started having painfulblisters of her feet and the lesions spread superiorly.


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Past Medical HistoryPast Medical History

ENTERITIS, REGIONAL, BOTH INTESTINES

COLECTOMY, HX OF

OSTEOPOROSIS

FISTULA, DIGESTIVE/GENITAL, FEMALE

RECTOVAGINALFISTULA

ANALFISTULA

PELVIC PAIN

ASHKENAZI JEWISH BACKGROUND

GYNECOLOGICALEXAMINATION, ROUTINE

HX, FAMILY, MALIGNANCY, BREAST OVARIAN CYST

ABSCESS, SKIN

SKIN RASH


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Medications ListMedications List

ACTONEL 5 MG TABS (RISEDRONATE SODIUM)

ATENOLOL 25 MG TABS (ATENOLOL) 1/2 tab daily

MULTIVITAMINS CAPS (MULTIPLEVITAMIN)

HUMIRA PEN 40 MG/0.8MLKIT (ADALIMUMAB) Inject 40mgm subcutaneous every other week

ZYRTECALLERGY 10 MG TABS (CETIRIZINE HCL) as directed

FLONASE 50 MCG/ACT SUSP (FLUTICASONE PROPIONATE) as directed

ASTELIN 137 MCG/SPRAY SOLN (AZELASTINE HCL) as directed

VITAMIN B-12 1000 MCG TABS (CYANOCOBALAMIN) 1 by mouth daily

CALCIUM 500-125 MG-UNIT TABS (CALCIUM CARBONATE-VITAMIN D) 1 by mouth bid

SPIRIVA HANDIHALER 18 MCG CAPS (TIOTROPIUM BROMIDEMONOHYDRATE) as directed

PULMICORT FLEXHALER 180 MCG/ACT INHA (BUDESONIDE) as directed

FLAGYL 250 MG TABS (METRONIDAZOLE) 1 by mouth qd

PRILOSEC OTC 20 MG TBEC (OMEPRAZOLEMAGNESIUM) 1 by mouth bid

CIPRO 500 MG TABS (CIPROFLOXACIN HCL) one by mouth bid for 14 days

ECONAZOLENITRATE 1 % CREA (ECONAZOLENITRATE) Apply to affected area twice daily until resolved

BACTROBAN2 % OINT (MUPIROCIN)Apply to affected area twice daily for 1 week

PERCOCET 5-325 MG TABS (OXYCODONE-ACETAMINOPHEN) Take 1 tab q8 hours as needed for pain

TRIAMCINOLONEACETONIDE 0.1 % OINT (TRIAMCINOLONEACETONIDE (TOP)) apply a thin film to affectedareas twice daily as directed

PREDNISONE 10 MG TABS (PREDNISONE) take 6 tab for 5 days then 5 tab for 5 days then 4 tab for 5 days then 3 tab for5 days then 2 tab for 5 days then 1 tab for 5 days then 1/2 tab

CLOBETASOL PROPIONATE 0.05 % OINT (CLOBETASOL PROPIONATE) apply to the affected area of the feet andlegs three times daily


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Family History

No FH of IBD;

Father with h/o Basal Cell Cancer, Melanoma

SubstanceHistory

Cigarette Use :None

ETOH Use : None

Social History

Married, no children


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Additional Work Up?Additional Work Up?


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Lab. Orders DoneLab. Orders Done

CultureCulture No organismNo organism

UrinalysisUrinalysis NormalNormal

BiopsyBiopsy


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BIOPSIESBIOPSIES


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0606--0404--2009 (A)2009 (A)


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0606--0404--2009 A2009 A


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0606--0404--2009 A2009 A


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0606--0404--20092009 -- BB


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0606--0404--20092009 -- BB


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0606--0404--20092009--BB


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0606--1010--20092009


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0606--1010--20092009


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0606--1010--20092009


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DDX based on HistologyDDX based on Histology

??


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Story ..Story ..

Treated with cephalexin and bactroban ointment.

Placed on Prednisone tapered initially and then placed on 30mg daily.

With medication more lesions erupting

Burning and pain which is not being controlled with percocet ( Oxycodone

& Acetaminophen)

Noticed that herleft knee became swollen 5 days ago without anyhistory of trauma. She is unable to wear shoes

Does take prilosec ( omeprazole ) and protection for her bones

Urinalysis is normal

Uncle has psoriasis


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Review of SystemsReview of Systems

Musculoskeletal: left knee pain and swelling

Neurologic:parasthesia and pain of the lower

limbs

Remaining systems dont have any significant

issues


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AssessmentAssessment

Pt with Crohn's disease being managed forLCV with Humira as presumedantigenic trigger. Now with flare, severe sxs per patient. Has not been wellcontrolled with tapering courses of prednisone starting at 20-30mg.

Had used Humira for Crohn's inconsistently throughout course of rash.

?Flares w Humira doses. D/C'd Humira May 09.

Biopsy shows inflamm injury to small vessels in dermis. There is howeverextensive neutrophilic accumulation in dermis, and so secondary ratherthan primary injury to vessels may also be considered.

Some other reasons why this eruption may not be true vasculitis:Eruptionis limited mostly to feet & ankles and interestingly involves soles of feet,which is unusual forLCV. Other dependent areas not involved, and this isalso surprising given chronicity of eruption and relative non-responsivenessto Rx; Eruption is distinctlypapulovesicular. There are also scattered non-hemorrhagic papulovesicles around the knees.


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AssessmentAssessment The patient also has a swollen and painful, but not hot, left knee. While arthralgias

may be noted with LCV, it's less typical to have an apparent inflamm arthritis and adistribution that is monoarticular with LCV.

Another diagnosis to consider would be Humira induced skin reaction and psoriaticarthritis like-reaction. The Id-like eruption is typical TNF-a induced eruptions.

Induction of PsA is also known to occur with the use of Biologics, although this hasbeen known to be the case more with T cell inhibiting biologic agents.

The patient has f/u with Dr. Demierre in coming weeks. Since Prednisone has beenthe treatment approach to this point, we will continue her on this regimen, but witha higher starting dose with taper.

Should the patient not respond to Prednisone while off of Humira, anotherconsideration could be using MTX to treat this problem as if it were

New onset Psoriasis and Psoriatic Arthritis.


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Prescriptions

CLOBETASOLPROPIONATE 0.05 % OINT

PREDNISONE 10 MG TABS (PRE

DN

ISONE

) take6

tabfor 5 days then 5 tab for 5 days then 4 tab for 5 days then 3 tab

for 5 days then 2 tab for 5 days then 1 tab for 5 days then 1/2

tab


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QuestionsQuestions If TNF alpha inhibitor causes Psoriasis in few cases, why weIf TNF alpha inhibitor causes Psoriasis in few cases, why we

get Psoriasis improvement with the same treatment?get Psoriasis improvement with the same treatment?

Is it drug reaction, Vasulitis, Psoriasiform reaction or TrueIs it drug reaction, Vasulitis, Psoriasiform reaction or True

Psoriasis?Psoriasis?

Acute Palmoplantar Pustular Psoriasis ofAndrews?Acute Palmoplantar Pustular Psoriasis ofAndrews?

Single knee joint pain, Psoriatic Arthritis?Single knee joint pain, Psoriatic Arthritis?

Is Psoriasiform eruption or Psoriasis clinical diagnosis orIs Psoriasiform eruption or Psoriasis clinical diagnosis or

histopathologic?histopathologic?


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Psoriasiform Eruption with TNFPsoriasiform Eruption with TNF

aplha Inhibitorsaplha Inhibitors

Review of LiteratureReview of Literature


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Psoriasiform Eruption with TNFPsoriasiform Eruption with TNF

aplha Inhibitorsaplha Inhibitors

First case of Psoriasiform eruption with Anti TNFFirst case of Psoriasiform eruption with Anti TNF

alpha in 2004, described by Verea et alalpha in 2004, described by Verea et al

Total Cases:70Total Cases:70 ( Archives of Dermatol, Dec. 2007)( Archives of Dermatol, Dec. 2007)

New onset Psoriasis orExacerbation of pre existingNew onset Psoriasis orExacerbation of pre existing

PsoriasisPsoriasis

TNFalpha Inhibitors role on Interferon alphaTNFalpha Inhibitors role on Interferon alpha( Cytoplasmoid Dendritic Cells Precursors )( Cytoplasmoid Dendritic Cells Precursors )


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Psoriasis and Pustular Dermatitis TriggeredPsoriasis and Pustular Dermatitis Triggered

by TNFby TNF-- Inhibitors in Patients WithInhibitors in Patients WithRheumatologic ConditionsRheumatologic Conditions

Gillian C. de Gannes, MD; Mehran Ghoreishi, MD, PhD; Janet Pope, MD, FRCPC;Gillian C. de Gannes, MD; Mehran Ghoreishi, MD, PhD; Janet Pope, MD, FRCPC;

Anthony Russell, MA, MB BChir, FRCPC; David Bell, MD, FRCPC; StewartAnthony Russell, MA, MB BChir, FRCPC; David Bell, MD, FRCPC; Stewart

Adams, MD, FRCPC; Kamran Shojania, MD, FRCPC; Magdalena Martinka, MD,Adams, MD, FRCPC; Kamran Shojania, MD, FRCPC; Magdalena Martinka, MD,

FRCPC; Jan P. Dutz, MD, FRCPCFRCPC; Jan P. Dutz, MD, FRCPC

Arch Dermatol.Arch Dermatol. 2007;143(2):2232007;143(2):223--231231


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There is mounting evidence that aThere is mounting evidence that a key innate immunekey innate immunepathway for triggering common human autoimmunepathway for triggering common human autoimmunediseasedisease, including psoriasis, involves, including psoriasis, involvesplasmacytoidplasmacytoid

dendritic cell precursors (PDCs) and type 1 interferondendritic cell precursors (PDCs) and type 1 interferon(IFN) production.(IFN) production.

We present herein a case series with clinical andWe present herein a case series with clinical andhistopathologic evidence of psoriasis in patients withhistopathologic evidence of psoriasis in patients withrheumatologic disease treated with TNFrheumatologic disease treated with TNF-- inhibitors.inhibitors.We propose that theWe propose that the cross regulation between TNFcross regulation between TNF--and IFN may have a role in the pathogenesis of thisand IFN may have a role in the pathogenesis of thisreaction.reaction.


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OBSERVATIONSOBSERVATIONSArch Dermatol.Arch Dermatol. 2007;143(2):2232007;143(2):223--231231

Immunohistochemical staining ofImmunohistochemical staining ofskin biopsyskin biopsy

specimens for myxovirusspecimens for myxovirus--resistance proteinA

resistance proteinA

(MxA, a surrogate marker for lesional type 1(MxA, a surrogate marker for lesional type 1

IFN activity) showedIFN activity) showed increased staining inincreased staining in

TNFTNF-- inhibitorinhibitorinduced psoriasis comparedinduced psoriasis compared

with psoriasis vulgaris.with psoriasis vulgaris.


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Patient 1Patient 1Arch Dermatol.Arch Dermatol. 2007;143(2):2232007;143(2):223--231231

4141--yearyear--old woman with rheumatoid arthritisold woman with rheumatoid arthritis,,developeddeveloped newnew--onset palmoplantar pustulosis after 26onset palmoplantar pustulosis after 26months of etanercept therapy.months of etanercept therapy.

Erythematous scaly plaques arose on her left heel (A)Erythematous scaly plaques arose on her left heel (A)

and left palm (B). C, Skin biopsy specimen showedand left palm (B). C, Skin biopsy specimen showedpsoriasiform epidermal hyperplasia withpsoriasiform epidermal hyperplasia withhyperkeratosis and confluent parakeratosis.hyperkeratosis and confluent parakeratosis.

There were a few telangiectatic blood vessels in theThere were a few telangiectatic blood vessels in the

papillary dermis associated with perivascularpapillary dermis associated with perivascularlymphocytic infiltrate and occasional neutrophils.lymphocytic infiltrate and occasional neutrophils.

TheThe findings were consistent with psoriasisfindings were consistent with psoriasis(hematoxylin(hematoxylin--eosin, original magnification x100).eosin, original magnification x100).


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41-year-old woman with rheumatoid arthritis, developed new-onset palmoplantar

pustulosis after 26 months of etanercept therapy

de Gannes, G. C. et al.ArchDermatol 2007;143:223-231.


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Patient 2Patient 2Arch Dermatol.Arch Dermatol. 2007;143(2):2232007;143(2):223--231231

5959--yearyear--old woman with juvenileold woman with juvenile--onset psoriatic arthritisonset psoriatic arthritis, developed, developedworsening of her preexisting psoriasis after 12 months of infliximabworsening of her preexisting psoriasis after 12 months of infliximabtherapytherapy

A,A, Guttate psoriasisGuttate psoriasis involved the trunk, especially the lower back.involved the trunk, especially the lower back.

B,B, Plaque psoriasisPlaque psoriasis on the dorsal and plantar aspects of the feet.on the dorsal and plantar aspects of the feet.

C, Skin biopsy specimen showed psoriasiform epidermal hyperplasiaC, Skin biopsy specimen showed psoriasiform epidermal hyperplasiaassociated with parakeratosis, telangiectatic blood vessels, perivascularassociated with parakeratosis, telangiectatic blood vessels, perivascularlymphocytic infiltrate, and occasional neutrophils in the papillary dermislymphocytic infiltrate, and occasional neutrophils in the papillary dermis

and lower epidermis.and lower epidermis.

TheThe findings were consistent with psoriasisfindings were consistent with psoriasis (hematoxylin(hematoxylin--eosin, originaleosin, originalmagnification x100).magnification x100).


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59-year-old woman with juvenile-onset psoriatic arthritis, developed worsening of

her preexisting psoriasis after 12 months of infliximab therapy



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Figure 3Figure 3Arch Dermatol.Arch Dermatol. 2007;143(2):2232007;143(2):223--231231

Patients withPatients with tumor necrosis factor (TNFtumor necrosis factor (TNF-- ) inhibitor) inhibitorinduced psoriasisinduced psoriasis (A(Aand B)and B) (original magnification x100) and(original magnification x100) and Psoriasis Vulgaris (C and D)Psoriasis Vulgaris (C and D)(original magnification x100) demonstrated(original magnification x100) demonstrated Epidermal MyxovirusEpidermal Myxovirus--Resistance Protein A (MxA) staining.Resistance Protein A (MxA) staining.

However, epidermalHowever, epidermal staining for MxA

wasstaining for MxA

was significantly more intensesignificantly more intense ininpatients treated with TNFpatients treated with TNF-- inhibitors.inhibitors.

Cytoplasmic MxACytoplasmic MxA staining wasstaining was noted in lesionalnoted in lesional dermal vasculature and indermal vasculature and inthe perivascular lymphocytic infiltratethe perivascular lymphocytic infiltrate only in psoriatic lesions fromonly in psoriatic lesions frompatients who underwent TNFpatients who underwent TNF-- inhibitor therapyinhibitor therapy (inset A and B) (original(inset A and B) (originalmagnification x400) andmagnification x400) and not in psoriatic lesions from patients withnot in psoriatic lesions from patients withpsoriasis vulgarispsoriasis vulgaris (inset C and D) (original magnification x400).(inset C and D) (original magnification x400).

For all panels, the avidinFor all panels, the avidin--biotin peroxidase staining system was used forbiotin peroxidase staining system was used forMxA along with hematoxylinMxA along with hematoxylin--eosin counterstain, as described in theeosin counterstain, as described in the"Methods" section."Methods" section.


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Patients with tumor necrosis factor {alpha} (TNF-{alpha}) inhibitor-induced

psoriasis (A and B) (original magnification x100) and psoriasis vulgaris (C and D)

(original magnification x100) demonstrated epidermal myxovirus-resistance

protein A (MxA) staining



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ConclusionsConclusions


New onset or severe exacerbation of psoriasisNew onset or severe exacerbation of psoriasis

is ais a rare complicationrare complication of TNF

of TNF

-- inhibitorinhibitortherapytherapy

The finding ofThe finding ofincreased production of IFNincreased production of IFN-- inin

TNFTNF-- inhibitorinhibitorinduced psoriasis is a possibleinduced psoriasis is a possible

pathophysiologic explanationpathophysiologic explanation for this reactionfor this reaction


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Psoriasiform Eruptions During AntiPsoriasiform Eruptions During AntiTNFTNF-- Treatment:Treatment:

Psoriasis or Not?Psoriasis or Not?Julien Seneschal, MD; SbastienLepreux, MD; Brigitte Milpied, MD; Thierry Schaeverbeke, MD, PhD; Alain Taeb, MD,Julien Seneschal, MD; SbastienLepreux, MD; Brigitte Milpied, MD; Thierry Schaeverbeke, MD, PhD; Alain Taeb, MD,

PhDPhD, Archives ofDerm, Archives ofDerm 20072007

Patch testPatch test with theE

uropean standard series and 2 antiwith theE

uropean standard series and 2 antiTNF

TNF

--molecules (etanercept and infliximab)molecules (etanercept and infliximab)

Reading at 48 hours and at day 8Reading at 48 hours and at day 8

Only 1 % reacted to the etanercept patch test at 48 hours withOnly 1 % reacted to the etanercept patch test at 48 hours with

edema and vesicles. Readings at day 8 showed a flare ofedema and vesicles. Readings at day 8 showed a flare of

dermatitis in 4 of the 8 patientsdermatitis in 4 of the 8 patients


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PsoriasiformEruptionsDuring AntiPsoriasiformEruptionsDuring AntiTNFTNF--

Treatment: Psoriasis or Not?Treatment: Psoriasis or Not?

Julien Seneschal, MD; Sbastien Lepreux, MD; Brigitte Milpied, MD; Thierry Schaeverbeke, MD, PhD;Julien Seneschal, MD; Sbastien Lepreux, MD; Brigitte Milpied, MD; Thierry Schaeverbeke, MD, PhD;Alain Taeb, MD, PhDAlain Taeb, MD, PhD, Archives ofDerm, Archives ofDerm 20072007

Histologic and immunohistochemical studies showed featuresHistologic and immunohistochemical studies showed featurescomparable with thecomparable with the initial psoriasiform lesionsinitial psoriasiform lesions

Moreover, the biopsy specimen of 1 patient contained aMoreover, the biopsy specimen of 1 patient contained amoderate number ofmoderate number ofeosinophilseosinophils

In contrast to the conclusions ofIn contrast to the conclusions ofde Gannes et alde Gannes et al thatthatpsoriasiform eruptions induced by antipsoriasiform eruptions induced by antiTNFTNF-- agentsagentsare true psoriasis, we propose thatare true psoriasis, we propose thatpsoriasiformpsoriasiformeruptions are "class effect" lesions, compatibleeruptions are "class effect" lesions, compatiblehistologically with lichenoid or spongiotichistologically with lichenoid or spongioticpsoriasiform drug eruptionspsoriasiform drug eruptions


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The Use ofPatch tests in DeterminingThe Use ofPatch tests in Determining

Hypersensitivity to Etanercept and Infliximab,Hypersensitivity to Etanercept and Infliximab,

2008,Archives ofDermatol2008,Archives ofDermatol

Contact allergens are under 500 DaContact allergens are under 500 Da; Larger molecules are unknown as; Larger molecules are unknown ascontact sensitizers and cannot penetratecontact sensitizers and cannot penetrate

Etanercept, infliximab, and adalimumab have molecular weights ofEtanercept, infliximab, and adalimumab have molecular weights of150150 000, 149000, 149 100, and 148100, and 148 000 Da, respectively000 Da, respectively, and are therefore very, and are therefore veryunlikely to cause positive patch test results.unlikely to cause positive patch test results.

InIn conclusionconclusion, we do not consider the described positive patch test results, we do not consider the described positive patch test resultssigns of hypersensitivity to etanercept or infliximab. Nevertheless, a skinsigns of hypersensitivity to etanercept or infliximab. Nevertheless, a skintest is a valuable tool with which to detect drug hypersensitivity, but thetest is a valuable tool with which to detect drug hypersensitivity, but thetest should be validated, the correct compound should be tested for, and thetest should be validated, the correct compound should be tested for, and thetest should be suitable for the drug considered.test should be suitable for the drug considered.

(Lidian L. A. Lecluse, MD; Gamze Piskin, MD, PhD; JanD. Bos, MD, PhD, FRCP)(Lidian L. A. Lecluse, MD; Gamze Piskin, MD, PhD; JanD. Bos, MD, PhD, FRCP)


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Rates of newRates of new--onset psoriasis in patientsonset psoriasis in patients

with rheumatoid arthritis receivingwith rheumatoid arthritis receivingantianti--tumour necrosis factor therapy:tumour necrosis factor therapy:

results from the British Society forresults from the British Society for

Rheumatology Biologics RegisterRheumatology Biologics Register

M J HarrisonM J Harrison11, WG Dixon, WG Dixon11, K DWatson, K DWatson11, Y King, Y King11, RGroves, RGroves22, KL, KL

HyrichHyrich11, D P M Symmons, D P M Symmons11,, and the British Society for Rheumatologyand the British Society for Rheumatology

Biologics Register ControlCentre Consortium on behalf of the BSRBRBiologics Register ControlCentre Consortium on behalf of the BSRBR

Published Online First: 2 April 2008Published Online First: 2 April 2008


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BackgroundBackground

AntiAnti--tumour necrosis factor (TNF) treatmentstumour necrosis factor (TNF) treatments

improve outcome in severe rheumatoidimprove outcome in severe rheumatoid

arthritis (RA) and are efficacious in psoriasisarthritis (RA) and are efficacious in psoriasis

and psoriatic arthritis.and psoriatic arthritis.

However recent case reports describe psoriasisHowever recent case reports describe psoriasis

occurring as an adverse event in patients withoccurring as an adverse event in patients with

RA receiving antiRA receiving anti--TNF therapy.TNF therapy.


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ObjectivesObjectives

Whether the incidence rate of psoriasis wasWhether the incidence rate of psoriasis washigher in patients with RA treated with antihigher in patients with RA treated with anti--TNF therapy compared to those treated withTNF therapy compared to those treated with

traditional diseasetraditional disease--modifying antirheumaticmodifying antirheumaticdrugs (DMARDs)drugs (DMARDs)

Also compared the incidence rates of psoriasis

Also compared the incidence rates of psoriasisbetween the three antibetween the three anti--TNF drugs licensed forTNF drugs licensed for

RA.RA.


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MethodsMethods

We studiedWe studied 9826 anti9826 anti--TNFTNF--treated and 2880treated and 2880

DMARDDMARD--treated patientstreated patients with severe RA from Thewith severe RA from The

British Society for Rheumatology Biologics RegisterBritish Society for Rheumatology Biologics Register

(BSRBR).(BSRBR). All patients reported with new onset psoriasisAll patients reported with new onset psoriasis as anas an

adverse eventadverse event were includedwere included in the analysis.in the analysis.

Incidence rates of psoriasis were calculated asIncidence rates of psoriasis were calculated as

events/1000 person years and compared usingevents/1000 person years and compared using

incidence rate ratios (IRR).incidence rate ratios (IRR).


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Results:Results:

In all, 25 incident cases of psoriasis in patients receiving antiIn all, 25 incident cases of psoriasis in patients receiving anti--TNF therapy and none in the comparison cohort were reportedTNF therapy and none in the comparison cohort were reported

between January 2001 and July 2007.between January 2001 and July 2007.

The absence of any cases in the comparison cohort precluded aThe absence of any cases in the comparison cohort precluded a

direct comparison; however the crude incidence rate ofdirect comparison; however the crude incidence rate ofpsoriasis in those treated with antipsoriasis in those treated with anti--TNF therapy was elevatedTNF therapy was elevatedat 1.04 (95% CI 0.67 to 1.54) per 1000 person years comparedat 1.04 (95% CI 0.67 to 1.54) per 1000 person years comparedto the rate of 0 (upper97.5% CI 0.71) per 1000 person years into the rate of 0 (upper97.5% CI 0.71) per 1000 person years inthe patients treated with DMARDs.the patients treated with DMARDs.

Patients treated with adalimumab had a significantlyPatients treated with adalimumab had a significantlyhigher rate of incident psoriasis compared to patientshigher rate of incident psoriasis compared to patientstreated with etanercept (IRR 4.6, 95% CI 1.7 to 12.1) andtreated with etanercept (IRR 4.6, 95% CI 1.7 to 12.1) andinfliximab (IRR 3.5, 95% CI 1.3 to 9.3).infliximab (IRR 3.5, 95% CI 1.3 to 9.3).


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ConclusionsConclusions

Incidence ofIncidence ofPsoriasisPsoriasis is increased in patientsis increased in patients

treatedtreated with antiwith anti--TNF therapyTNF therapy

Incidence may beIncidence may be higherhigherin patients treatedin patients treated

with adalimumabwith adalimumab


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Bolognia JLBolognia JL, Jorizzo, Rapini RP. Elsevier Science,, Jorizzo, Rapini RP. Elsevier Science,

London,London, 20082008, Chapter 128, Chapter 128

A variety of skin lesions or diseases have been reported as potential adverseA variety of skin lesions or diseases have been reported as potential adversereactions to antireactions to anti--TNF agents, includingTNF agents, including adalimumabadalimumab

Recent reports ofRecent reports ofnewnew--onset psoriasisonset psoriasis have appearedhave appeared

TheThe exact mechanismexact mechanism for this reaction is not knownfor this reaction is not known

Cutaneous small vessel vasculitisCutaneous small vessel vasculitis might complicate therapy with TNFmight complicate therapy with TNFblocking agents, but the reports are most frequent in patients withblocking agents, but the reports are most frequent in patients withrheumatoid arthritis, a disease known to be associated with vasculitisrheumatoid arthritis, a disease known to be associated with vasculitis

Lastly, multiple cases ofLastly, multiple cases ofinterstitial granulomatous dermatitisinterstitial granulomatous dermatitis have beenhave beenobserved in patients on various antiobserved in patients on various anti--TNF agentsTNF agents


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Interferon AlphaInterferon Alpha

Interferon alpha: major role in Psoriasis inductionInterferon alpha: major role in Psoriasis induction

Plasmacytoid dendritic cells (pDC)Plasmacytoid dendritic cells (pDC) are a rare subtype of circulating dendritic cellsare a rare subtype of circulating dendritic cellsfound in the blood as well as in peripheral lymphoid organsfound in the blood as well as in peripheral lymphoid organs

pDC produce large amounts of (mainly IFNpDC produce large amounts of (mainly IFN-- (alpha) and IFN (alpha) and IFN-- (beta)), (beta)), which arewhich arecritical pleiotropic anticritical pleiotropic anti--viral compounds mediating a wide range of effectsviral compounds mediating a wide range of effects

Interferons are produced in response to the presence of doubleInterferons are produced in response to the presence of double--stranded RNA,stranded RNA, a keya keyindicator of viral infection.indicator of viral infection.

Interferons assist the immune response by inhibiting viral replication within hostInterferons assist the immune response by inhibiting viral replication within host

cells, activating natural killer cells and macrophages, increasing antigencells, activating natural killer cells and macrophages, increasing antigenpresentation to lymphocytes, and inducing the resistance of host cells to viralpresentation to lymphocytes, and inducing the resistance of host cells to viral

infection.infection.


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TNFTNF--Alpha, INFAlpha, INF--Apha,Apha,

CXCR3CXCR3 TNFAlpha and IFNTNFAlpha and IFN-- Alpha:Alpha:

1) Inhibit Plasmacytoid Dendritic Cells(PDC)1) Inhibit Plasmacytoid Dendritic Cells(PDC)

2) Inhibit release of IFN2) Inhibit release of IFN--Alpha by PDCAlpha by PDC

TNFTNF-- Alpha inhibition & CXCR3:Alpha inhibition & CXCR3:

1)CXCR3 expression in circulatig T cells1)CXCR3 expression in circulatig T cells2) Skin homing of these cells2) Skin homing of these cells


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Why not LCV?Why not LCV?

Morphology of lesionsMorphology of lesions

Distribution of lesionsDistribution of lesions

Inflammatory MonoarticularArthritisInflammatory MonoarticularArthritis

Presence of vessel damage may be secondary (e.g.Presence of vessel damage may be secondary (e.g.PG, Sweets)PG, Sweets)

Inflammatory dermatoses always require CPC by theInflammatory dermatoses always require CPC by theclinicianclinician


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Why Psoriasis or Ps. ArthtitisWhy Psoriasis or Ps. Arthtitis

Morphology and distribution of lesionsMorphology and distribution of lesions

Inflammatory joint involvement with swellingInflammatory joint involvement with swelling

Literature case reports and studiesLiterature case reports and studies


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ReferencesReferences

Archives of DermatologyArchives of Dermatology

Bolognia JL, Jorizzo, Rapini RP. Elsevier Science, London,Bolognia JL, Jorizzo, Rapini RP. Elsevier Science, London,

2008, Chapter 1282008, Chapter 128

Lidian L. A. Lecluse, MD; Gamze Piskin, MD, PhD; Jan D. Bos, MD, PhD,Lidian L. A. Lecluse, MD; Gamze Piskin, MD, PhD; Jan D. Bos, MD, PhD,

FRCPFRCP


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There is nothing like a dreamThere is nothing like a dreamto create the futureto create the future

(Victor Hugo)(Victor Hugo)


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Enjoy your dreamsEnjoy your dreams


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Thanks toThanks to

Dr. Amit GargDr. Amit Garg for patient discussion and photosfor patient discussion and photos

Dr. Lin GoldbergDr. Lin Goldberg for slides discussion and supportfor slides discussion and support

Dr. Ron YaarDr. Ron Yaar for slides discussionfor slides discussion

Dr. Thomas RuengerDr. Thomas Ruenger for this learning activityfor this learning activity

All ColleaguesAll Colleagues for carefull attention and passionfor carefull attention and passion

clinical seminar 13 jluy 2009

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