Spectrophotometric intracutaneous analysis as an early non ...

7
ORIGINAL ARTICLE Spectrophotometric intracutaneous analysis as an early non-invasive predictor of efficacy in the phototherapy of psoriasis Ljubomir Novakovic ´ 1 , Symon Cotton 2 & John L. M. Hawk 1 1 Photobiology Unit, St John’s Institute of Dermatology, St Thomas’ Hospital, London, UK, and 2 Astron Clinica, Cambridge, UK Key words: narrowband UVB; psoriasis; PUVA; SIAscopy; spectrophotometric intracutaneous analysis Correspondence: Dr Ljubomir Novakovic ´, Photobiology Unit, St. John’s Institute of Dermatology, St. Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK. Tel: 144 20 71886389 Fax:144 20 79281621 e-mail: [email protected] Accepted for publication: 5 November 2008 Conflicts of interest: None declared. Summary Background: Phototherapy is generally effective for psoriasis but individual responsiveness and optimal treatment duration for disease clearance are unpredictable. However, easy, rapid and non-invasive plaque assessment by spectrophotometric intracutaneous analysis (SIAscopy), a novel multispectral skin imaging technique, may now make prediction feasible. Objectives: The early prediction of psoriatic plaque clearance during phototherapy by SIAscopy. Methods: Sixteen psoriatic plaques in 10 psoriasis patients were serially assessed SIAscopically during phototherapy for punctate dots representing the dilated papillary dermal blood vessels characteristic of active psoriasis, and the results compared with the clinical findings. Results: All plaques showing full SIAscopic clearance at early follow-up also showed complete or almost complete clinical clearance, and remained the same thereafter. All showing no SIAscopic clearance at early follow-up showed at most partial clinical clearance, and also remained the same thereafter. All showing only partial SIAscopic clearance at early follow-up also showed just partial clinical clearance, but then generally progressed to full SIAscopic and clinical clearance. Conclusions: SIAscopy of psoriatic plaques at early follow-up during patient phototherapy enables good prediction of likely later clinical clearance, thereby potentially avoiding unnecessary further treatment. A larger confirmatory study is now needed. P soriasis, a chronic, hyperproliferative, immunological skin disorder affecting 1–2% of the population worldwide, most commonly demonstrates well-demarcated erythematous plaques with adherent white or silvery scales. Histology typically shows extended rete ridges and elongated dermal papillae containing dilated and tortuous capillaries. Biopsy for such histology is inconvenient, however, and these characteristic abnormalities can now be identified easily and non-invasively instead by spectrophotometric intracutaneous analysis (SIA), a novel technique reliably able to identify so-called punctate dots representing the typical psoriatic dilated capillary tips between the broadened rete ridges (1) (Figs 1 and 2). Phototherapy, whether narrowband UVB (NB-UVB) or psoralen photochemotherapy (PUVA), is an excellent treatment for 80–90% of psoriatic patients unresponsive to topical treatments. However, the likely outcome of such therapy is difficult to assess early on, unless perhaps by recurrent invasive biopsy and histological assessment, but such an approach would be inappropriate. Thus, phototherapy courses may become unnecessarily long and expensive for patients, treatment staff and treatment centres, increase the risk of patient skin ageing and cancer, and delay patient transfer to other therapies. Therefore, an easy, rapid, non-invasive technique permitting early, accurate prediction of future therapeutic efficacy would be invaluable. The SIAscope is a multispectral imaging device using the specific absorptive and scattering properties in skin of molecular radiation absorbers and larger structures, which interact uniquely with light to form distinct remittance patterns over the 400–1000 nm waveband, thereby providing rapid, non- invasive, in vivo information on gross skin structure and pathology (2). As a result, epidermal and dermal pigment distribution, lesional microcirculation patterns and volumes, dermo-epidermal junction architecture, and dermal collagen status may all be assessed, often enabling for example the reliable diagnosis of malignant melanoma without the need for biopsy (3). SIAscopic analysis takes about 10 s, 5 s to scan the skin and 5 s for information processing. SIAscope scans produce lesional colour images comparable to those seen on dermoscopy, as well as maps, or SIAgraphs, of skin collagen distribution, vascularity and melanin, compiled from readings at about a million different lesional points. SIAgraphs of normal and psoriatic skin respectively are shown in Figs 1 and 2, the punctate dots on the psoriatic SIAgraph representing dermal papillary vessel tips. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 PPP 411 B Dispatch: 11.12.08 Journal: PPP CE: Sonal/Guruprasad Journal Name Manuscript No. Author Received: No. of pages: 5 Te: Bindu/mini 1 r 2008 The Authors Journal compilation r 2008 Blackwell Munksgaard Photodermatology, Photoimmunology & Photomedicine ]], 1–5 PPP 411 (BWUK PPP 411.PDF 11-Dec-08 21:53 1187329 Bytes 5 PAGES n operator=gn.sreedhara)

Transcript of Spectrophotometric intracutaneous analysis as an early non ...

Page 1: Spectrophotometric intracutaneous analysis as an early non ...

O R I G I N A L A R T I C L E

Spectrophotometric intracutaneous analysis as an early non-invasive

predictor of efficacy in the phototherapy of psoriasisLjubomir Novakovic1, Symon Cotton2 & John L. M. Hawk1

1Photobiology Unit, St John’s Institute of Dermatology, St Thomas’ Hospital, London, UK, and 2Astron Clinica, Cambridge, UK

Key words:narrowband UVB; psoriasis; PUVA;

SIAscopy; spectrophotometric

intracutaneous analysis

Correspondence:Dr Ljubomir Novakovic, Photobiology Unit, St. John’s

Institute of Dermatology, St. Thomas’ Hospital,

Lambeth Palace Road, London SE1 7EH, UK.

Tel: 144 20 71886389

Fax:144 20 79281621

e-mail: [email protected]

Accepted for publication:5 November 2008

Conflicts of interest:None declared.

Summary

Background: Phototherapy is generally effective for psoriasis but individual responsiveness and

optimal treatment duration for disease clearance are unpredictable. However, easy, rapid and

non-invasive plaque assessment by spectrophotometric intracutaneous analysis (SIAscopy), a

novel multispectral skin imaging technique, may now make prediction feasible.

Objectives: The early prediction of psoriatic plaque clearance during phototherapy by

SIAscopy.

Methods: Sixteen psoriatic plaques in 10 psoriasis patients were serially assessed SIAscopically

during phototherapy for punctate dots representing the dilated papillary dermal blood

vessels characteristic of active psoriasis, and the results compared with the clinical findings.

Results: All plaques showing full SIAscopic clearance at early follow-up also showed complete

or almost complete clinical clearance, and remained the same thereafter. All showing no

SIAscopic clearance at early follow-up showed at most partial clinical clearance, and also

remained the same thereafter. All showing only partial SIAscopic clearance at early follow-up

also showed just partial clinical clearance, but then generally progressed to full SIAscopic and

clinical clearance.

Conclusions: SIAscopy of psoriatic plaques at early follow-up during patient phototherapy

enables good prediction of likely later clinical clearance, thereby potentially avoiding

unnecessary further treatment. A larger confirmatory study is now needed.

P soriasis, a chronic, hyperproliferative, immunological skin

disorder affecting 1–2% of the population worldwide, most

commonly demonstrates well-demarcated erythematous plaques

with adherent white or silvery scales. Histology typically shows

extended rete ridges and elongated dermal papillae containing

dilated and tortuous capillaries. Biopsy for such histology is

inconvenient, however, and these characteristic abnormalities

can now be identified easily and non-invasively instead by

spectrophotometric intracutaneous analysis (SIA), a novel

technique reliably able to identify so-called punctate dots

representing the typical psoriatic dilated capillary tips between

the broadened rete ridges (1) (Figs 1 and 2).

Phototherapy, whether narrowband UVB (NB-UVB) or

psoralen photochemotherapy (PUVA), is an excellent treatment

for 80–90% of psoriatic patients unresponsive to topical

treatments. However, the likely outcome of such therapy is

difficult to assess early on, unless perhaps by recurrent invasive

biopsy and histological assessment, but such an approach would

be inappropriate. Thus, phototherapy courses may become

unnecessarily long and expensive for patients, treatment staff

and treatment centres, increase the risk of patient skin ageing and

cancer, and delay patient transfer to other therapies. Therefore, an

easy, rapid, non-invasive technique permitting early, accurate

prediction of future therapeutic efficacy would be invaluable.

The SIAscope is a multispectral imaging device using the

specific absorptive and scattering properties in skin of molecular

radiation absorbers and larger structures, which interact uniquely

with light to form distinct remittance patterns over the

400–1000 nm waveband, thereby providing rapid, non-

invasive, in vivo information on gross skin structure and

pathology (2). As a result, epidermal and dermal pigment

distribution, lesional microcirculation patterns and volumes,

dermo-epidermal junction architecture, and dermal collagen

status may all be assessed, often enabling for example the

reliable diagnosis of malignant melanoma without the need for

biopsy (3). SIAscopic analysis takes about 10 s, 5 s to scan the

skin and 5 s for information processing.

SIAscope scans produce lesional colour images comparable to

those seen on dermoscopy, as well as maps, or SIAgraphs, of skin

collagen distribution, vascularity and melanin, compiled from

readings at about a million different lesional points. SIAgraphs of

normal and psoriatic skin respectively are shown in Figs 1 and 2,

the punctate dots on the psoriatic SIAgraph representing dermal

papillary vessel tips.

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

P P P 4 1 1 B Dispatch: 11.12.08 Journal: PPP CE: Sonal/Guruprasad

Journal Name Manuscript No. Author Received: No. of pages: 5 Te: Bindu/mini

1

r 2008 The Authors

Journal compilation r 2008 Blackwell Munksgaard � Photodermatology, Photoimmunology & Photomedicine ]], 1–5

PPP 411(BW

UK

PPP

411

.PD

F 11

-Dec

-08

21:5

3 11

8732

9 B

ytes

5 P

AG

ES

n op

erat

or=

gn.s

reed

hara

)

Page 2: Spectrophotometric intracutaneous analysis as an early non ...

Methods

To attempt to evaluate SIAscopic usefulness, this pilot study was

undertaken at St Thomas’ Hospital, London, UK. Approval for the

work was obtained from the St Thomas’ Hospital Ethics

Committee and 10 patients with widespread psoriasis, seven

undergoing phototherapy with NB-UVB and three with PUVA,

were imaged with the SIAscope before and during treatment for

punctate dots over either one or two plaques on the trunk or

upper limbs (Table 1). Psoriasis-unaffected areas in the same

patients were used as control sites. Exclusion criteria were pre-

vious phototherapy within the past 6 months and concomitant

systemic or topical treatment for psoriasis. Both NB-UVB and

PUVA were administered twice weekly. Patients were reviewed at

follow up at 4–6 weeks, then 8–12 weeks, when their psoriasis

overall was assessed clinically and the one or two previously

chosen plaques on the trunk or limbs independently evaluated

with the SIAscope.

Results (Table 1)

Sixteen psoriatic plaques in 10 patients with widespread psoriasis

were evaluated, either one or two in each patient. At initial

presentation, all 16 demonstrated punctate dots on SIAgraphy

but none at control non-affected sites. Seven were treated with

NB-UVB, two of these having two plaques assessed, and three

with PUVA, all having two plaques assessed (Table 1).

With respect to plaques, all five showing full SIAscopic

clearance (Fig. 3) at first follow-up at 4–6 weeks showed

complete or almost complete clinical clearance, and remained

the same, along with five others also now clear, at second follow-

up at 8–12 weeks. All three plaques showing no SIAscopic

clearance at first follow-up (Fig. 4) showed at most just some

clinical clearance, and again remained the same at second follow-

up. All seven plaques showing only partial SIAscopic clearance at

first follow-up (Fig. 5) showed just partial clinical clearance, as

did two still at second follow-up, the other five having now

progressed to full SIAscopic and clinical clearance. With respect

to patients, two showing full SIAscopic and clinical clearance in

one or two plaques, respectively, at first follow-up remained clear

at second follow-up, while another showing full SIAscopic but

just some clinical clearance in one plaque at first follow-up

showed continuing full SIAscopic but now complete clinical

clearance at second follow-up. One patient showing no

SIAscopic and just some clinical clearance at first follow-up still

showed no SIAscopic and just some clinical clearance at second

follow-up. Three patients showing partial SIAscopic and clinical

clearance in five plaques at first follow-up progressed to full

SIAscopic and complete or almost complete clinical clearance at

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

Fig. 2. Spectrophotometric intracutaneous analysis (SIA) graph of

psoriasis-affected skin before phototherapy. Note the presence of many

punctate dots, some examples of which are indicated by arrows.

Fig. 1. Spectrophotometric intracutaneous analysis (SIA) graph of

normal skin. Note diffuse and regular distribution of haemoglobin.

r 2008 The Authors

Journal compilation r 2008 Blackwell Munksgaard � Photodermatology, Photoimmunology & Photomedicine ]], 1–52

Novakovic et al.

PPP 411(BW

UK

PPP

411

.PD

F 11

-Dec

-08

21:5

3 11

8732

9 B

ytes

5 P

AG

ES

n op

erat

or=

gn.s

reed

hara

)

Page 3: Spectrophotometric intracutaneous analysis as an early non ...

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

Table 1. Details of patients, and their numbers of plaques, plaque sites, treatments, SIAscope readings and degrees of clinical clearance during the study

PatientPlaquenumbers Location

PUVA orNB-UVB

First follow-up visit (4–6 Weeks) Second follow-up visit (8–12 Weeks)

SIAscope Clinical SIAscope Clinical

1 2 Trunk/upper arm NB-UVB F/F CC/CC F/F CC/CC2 1 Thigh NB-UVB N I N I

3 1 Thigh NB-UVB P I F CC

4 2 Upper arm/trunk NB-UVB P/F AC/AC P/F AC/CC

5 1 Trunk NB-UVB F CC F CC6 2 Trunk/trunk PUVA P/P I/I F/F AC/AC

7 2 Trunk/forearm NB-UVB P/P I/I F/F CC/CC

8 1 Trunk NB-UVB F I F CC9 2 Trunk/trunk PUVA N/P I/I N/P I/I

10 2 Trunk/trunk PUVA N/P I/I N/P I/I

Clinical evaluation:

CC, completely clear;

AC, almost clear;

I, improved.

SIAscope readings:

F, full clearance;

P, partial clearance;

N, no clearance.

Fig. 3. Spectrophotometric intracutaneous analysis (SIA) graph showing

full psoriasis clearance. Note the absence of punctate dots.

Fig. 4. Spectrophotometric intracutaneous analysis (SIA) graph showing

failure of psoriatic clearance following phototherapy. Note the persistent

punctate dots, some examples of which are indicated by arrows.

3

r 2008 The Authors

Journal compilation r 2008 Blackwell Munksgaard � Photodermatology, Photoimmunology & Photomedicine ]], 1–5

Spectrophotometric intracutaneous analysisQ1

PPP 411(BW

UK

PPP

411

.PD

F 11

-Dec

-08

21:5

3 11

8732

9 B

ytes

5 P

AG

ES

n op

erat

or=

gn.s

reed

hara

)

Page 4: Spectrophotometric intracutaneous analysis as an early non ...

second follow-up. One further patient with two plaques,

however, showed partial SIAscopic and clinical clearance in one

plaque and full SIAscopic and near full clinical clearance in the

other at first follow-up and remained essentially the same at

second follow-up, while a final two again showed partial

SIAscopic and clinical clearance in one plaque, but on this

occasion no SIAscopic and little clinical clearance in the other at

first follow-up, and again remained the same at second follow-

up. These results appeared independent of whether NB-UVB or

PUVA was used.

Discussion

SIAscopy was originally developed to help provide a reliable

diagnosis of malignant melanoma without the need for invasive

biopsy (3), but has gradually proved able to assess other

superficial cutaneous abnormalities also. Thus, we have shown

previously that the presence of punctate dots on SIAgraphs is

specific for psoriasis (1), a fact confirmed in the present study,

with all 16 psoriatic plaques having again demonstrated punctate

dots on SIAscopy before phototherapy.

The current study has also shown that SIAscopy may well

enable the avoidance of unnecessary phototherapy in

unresponsive patients, thus saving patient, staff and treatment

unit time and money, preventing long-term cumulative, adverse

radiation effects on patient skin and enabling early patient

transfer to other treatment. Thus, any patient with one or both

of two plaques showing full SIAscopic (and clinical) clearance,

and any with one or both of two plaques showing no SIAscopic

(or significant clinical) clearance at first follow-up at 4–6 weeks,

remained the same at second follow-up at 8–12 weeks, such that

phototherapy might have been terminated in these patients at

first follow-up. Any patient with one or both of two plaques

showing only partial SIAscopic (and clinical) clearance at first

follow-up progressed to full SIAscopic and also clinical clearance

at second follow-up, such that phototherapy should have been

continued at first follow-up in these patients. However, any

patient with each of two plaques showing different SIAscopic

(and clinical) appearances at first follow-up was less easily

assessible, but although the SIAscopically worse plaque at first

follow-up appeared to predict the eventual outcome best,

phototherapy should also have been continued in these patients

because of the predictive uncertainty.

Based on these various possible outcomes, therefore, a simple

but useful algorithm has been proposed by us for use at first

patient phototherapy follow-up at 4–6 weeks, and indicates

where continuation of the irradiation course might be

appropriate, or instead its termination with a change to other

therapy (Fig. 6).

Although this has only been a small study, such that the results

should only be considered preliminary, it seems likely, given that

the punctate dots which either disappeared on SIAscopy or are

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

Fig. 5. Spectrophotometric intracutaneous analysis (SIA) graph of partial

clearance with phototherapy. Note the fewer punctate dots, some examples

of which are indicated by arrows, and the increased vessel numbers.

Fig. 6. Suggested algorithm to assist future treatment approach based on

SIAscopic assessment of psoriasis patients at first phototherapy follow up

at 4–6 weeks.

Q3

r 2008 The Authors

Journal compilation r 2008 Blackwell Munksgaard � Photodermatology, Photoimmunology & Photomedicine ]], 1–54

Novakovic et al.

PPP 411(BW

UK

PPP

411

.PD

F 11

-Dec

-08

21:5

3 11

8732

9 B

ytes

5 P

AG

ES

n op

erat

or=

gn.s

reed

hara

)

Page 5: Spectrophotometric intracutaneous analysis as an early non ...

not characteristic of active psoriasis, that the outcome of NB-UVB

or PUVA therapy in psoriasis may be predictable early in the

treatment course. Thus, all plaques clear at 4–6 weeks remained so

at 8–12 weeks, while none showing no clearance progressed any

further, suggesting these courses should have ceased forthwith.

Those showing partial clearance at 4–6 weeks nearly all progressed

to full clearance with continuing treatment, suggesting that

phototherapy should indeed have been continued in this group.

However, it is clear that several plaques from different body sites

rather than just one or two as in this study should be serially

assessed in all patients to give a more valid prediction of likely

patient response, and this is easily manageable, given that SIAscopy

is such a simple and rapid procedure.

A larger study evaluating more plaques in more patients is

now needed to confirm the encouraging findings produced by

this pilot study.

Summary statement

The rapid, easy, non-invasive procedure of SIAscopy is very likely

an important advance in predicting psoriatic phototherapeutic

efficacy, potentially permitting early treatment termination to

save time and money, minimize patient adverse effects, and

enable early initiation of other therapy. Thus, all patients in this

study with early SIAscopic and clinical clearance, and all with no

SIAscopic even if some clinical clearance, remained the same

thereafter, and could have stopped therapy early. Of those with

partial early SIAscopic and clinical clearance, nearly all progressed

to full clearance, such that they should also have carried on.

A larger confirmatory study is now needed.

References

1. Novakovic L, Hawk J. Spectrophotometric intracutaneous analy-

sis Q2: a novel technique in the differential diagnosis of psoriasis and

eczema. Br J Dermatol 2002; 147 (Suppl. 62): 104.

2. Cotton S. A non-invasive imaging system for assisting in the

diagnosis of malignant melanoma. PhD Thesis. Faculty of Science,

University of Birmingham, UK 1998.

3. Moncrieff M, Cotton S, Claridge E, Hall P. Spectrophotometric

intracutaneous analysis: a new technique for imaging pigmented

skin lesions. Br J Dermatol 2002; 146: 448–457.

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

5

r 2008 The Authors

Journal compilation r 2008 Blackwell Munksgaard � Photodermatology, Photoimmunology & Photomedicine ]], 1–5

Spectrophotometric intracutaneous analysisQ1

PPP 411(BW

UK

PPP

411

.PD

F 11

-Dec

-08

21:5

3 11

8732

9 B

ytes

5 P

AG

ES

n op

erat

or=

gn.s

reed

hara

)

Page 6: Spectrophotometric intracutaneous analysis as an early non ...

Author Query Form

_______________________________________________________

_______________________________________________________

Dear Author,

During the copy-editing of your paper, the following queries arose. Please respond to these by marking up your proofs with the necessary changes/additions. Please write your answers clearly on the query sheet if there is insufficient space on the page proofs. If returning the proof by fax do not write too close to the paper's edge. Please remember that illegible mark-ups may delay publication.

Journal       pppArticle       411

Query No. Description Author Response

Q1

  AUTHOR: A running head short title was not supplied; please check if this one is suitable and, if not, please supply a short title that can be used instead.   

Q2  AUTHOR: If this is not a one-page article please supply the last page for reference [1].   

Q3Supplies figure is not of good qualilty. Please provide good quality figure.

 

Q4

AQ: We have processed Figure 1-5 in colour. If  Figure 1-5 are to be published in colour, then, download the Colour Work Agreement form from the path: <http://www.blackwellpublishing.com/pdf/sN_Sub2000_X_CoW.pdf> 

 

     

     

     

     

     

     

Page 7: Spectrophotometric intracutaneous analysis as an early non ...

MARKED PROOF

Please correct and return this set

Instruction to printer

Leave unchanged under matter to remain

through single character, rule or underline

New matter followed byor

or

or

or

or

or

or

or

or

and/or

and/or

e.g.

e.g.

under character

over character

new character new characters

through all characters to be deleted

through letter orthrough characters

under matter to be changedunder matter to be changedunder matter to be changedunder matter to be changedunder matter to be changed

Encircle matter to be changed

(As above)

(As above)

(As above)

(As above)

(As above)

(As above)

(As above)

(As above)

linking characters

through character orwhere required

between characters orwords affected

through character orwhere required

or

indicated in the marginDelete

Substitute character orsubstitute part of one ormore word(s)

Change to italicsChange to capitalsChange to small capitalsChange to bold typeChange to bold italicChange to lower case

Change italic to upright type

Change bold to non-bold type

Insert ‘superior’ character

Insert ‘inferior’ character

Insert full stop

Insert comma

Insert single quotation marks

Insert double quotation marks

Insert hyphenStart new paragraph

No new paragraph

Transpose

Close up

Insert or substitute spacebetween characters or words

Reduce space betweencharacters or words

Insert in text the matter

Textual mark Marginal mark

Please use the proof correction marks shown below for all alterations and corrections. If you

in dark ink and are made well within the page margins.wish to return your proof by fax you should ensure that all amendments are written clearly