Assessment of treatment effects on digital ulcer and blood perfusion by laser speckle contrast analysis in a patient affected by systemic sclerosis

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RADIOLOGICAL VIGNETTE

134 Reumatismo 3/2017 RADIOLOGICAL VIGNETTE

Assessment of treatment effects

on digital ulcer and blood perfusion

by laser speckle contrast analysis

in a patient affected by systemic sclerosis

B. Ruaro, S. Paolino, C. Pizzorni, M. Cutolo, A. Sulli

Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

SUMMARY

Laser speckle contrast analysis (LASCA) is a good tool to evaluate the variation in peripheral blood perfu-sion during long-term follow-up and is able to safely monitor digital ulcer evolution in scleroderma patients. It evaluates blood perfusion in different areas within the skin lesions and surrounding them during standard treatment.

Key words: Systemic sclerosis, LASCA, blood perfusion

Reumatismo, 2017; 69 (3): 134-136

n RADIOLOGICAL VIGNETTE

A 57 year-old female (M.E.) presented to our Rheumatology Outpatient Service in February 2012, with a digital periungual ulcer on her third left finger, severe Rayn-aud’s phenomenon and joint pain that had been affecting her hand and wrists for a two-year period. Her condition had previ-ously been controlled by her GP with pain-killers. She was an ex-smoker and, in 2011, had a traumatic fracture of the second fin-ger of her left hand.

Physical examination evidenced a periun-gual ulcer on her third left fingertip, puffy fingers, Raynaud’s phenomenon, initial sclerodactily and facial telangiectasia. She also had a swollen right wrist and some painful metacarpophalangeal joints. Laboratory tests revealed positive antinu-clear antibodies (titre 1:640, with a homo-geneous and nucleolar indirect immune-fluorescence pattern) and facial telangiec-tasia. Blood tests evidenced a rise in the in-flammatory markers: erythrocyte sedimen-tation rate, C-reactive protein and gamma globulin protein percentage (54 mm/1 h, 10 mg/L, and 21% respectively).

More-over, there was a slight consumption of C3 complement fraction (0.84 g/L). The other laboratory tests, which included renal and liver function tests, rheumatoid factor and anti-citrullinated protein antibodies, were unremarkable. Nailfold videocapillaros-copy (NVC) was performed to evaluate Raynaud’s phenomenon (1-4). The NVC examination demonstrated a scleroderma-pattern, characterized by an early pattern of microangiopathy, with a few giant capil-laries, a few capillary haemorrhages and a relatively well-preserved capillary distribu-tion, without evident capillary loss (Figure 1A) (5-7).

In 2012 a diagnosis of systemic sclerosis (SSc) was made according to the LeRoy 2001 criteria (8). Disease severity was as-sessed by several instrumental examina-tions: chest X-ray, spirometry, oesopha-geal manometry, which were all within the normal range, renal Doppler echography that showed normal renal artery resistive indexes, and heart echography that showed no pathological findings; estimated sPAP was 27 mmHg.

Treatment was planned with iloprost (continuous 5-day intravenous infusion),

Corresponding author

Barbara Ruaro Research Laboratory and Academic Division of Clinical Rheumatology Department of Internal Medicine, University of Genova, IRCCS Ospedale Policlinico San Martino viale Benedetto XV 6 16132 Genova, Italy E-mail: barbara.ruaro@yahoo.it Reumatismo, 2016; 69 (3): 134-136

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RADIOLOGICAL VIGNETTE

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RADIOLOGICAL VIGNETTE

A 57 year-old female (M.E.) presented to

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A 57 year-old female (M.E.) presented to our Rheumatology Outpatient Service in

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our Rheumatology Outpatient Service in February 2012, with a digital periungual

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February 2012, with a digital periungual ulcer on her third left finger, severe Rayn

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ulcer on her third left finger, severe Rayn aud’s phenomenon and joint pain that had

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aud’s phenomenon and joint pain that had been affecting her hand and wrists for a

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been affecting her hand and wrists for a two-year period. Her condition had previ

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two-year period. Her condition had previ

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ously been controlled by her GP with

pain-Non-commercial

ously been controlled by her GP with pain-killers. She was an ex-smoker and, in 2011,

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killers. She was an ex-smoker and, in 2011, had a traumatic fracture of the second fin

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had a traumatic fracture of the second fin

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Laser speckle contrast analysis (LASCA) is a good tool to evaluate the variation in peripheral blood perfu

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Laser speckle contrast analysis (LASCA) is a good tool to evaluate the variation in peripheral blood perfu

sion during long-term follow-up and is able to safely monitor digital ulcer evolution in scleroderma patients.

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sion during long-term follow-up and is able to safely monitor digital ulcer evolution in scleroderma patients.

valuates blood perfusion in different areas within the skin lesions and surrounding them during standard

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Reumatismo 3/2017 135

Assessment of treatment effects on digital ulcer and blood perfusion

bosentan (65 mg twice daily which was in-creased after one month to 125 mg twice daily), methotrexate (10 mg/week) and an-algesic drugs (tramadol 50 mg/day) (9-10). Before starting the pharmacological treat-ment, laser speckle contrast analysis (LAS-CA) was performed to evaluate both the extension and perfusion of the ulcer area (Figure 2A) (11-14).

Her symptoms gradually improved over a two-month period, with progressive nor-malization of the inflammatory markers. Her digital ulcer made progressive recov-ery and her skin blood perfusion increased, as evidenced by a control LASCA exami-nation (Figure 2B).

During a follow-up visit in 2014, the pa-tient had an increase in renal artery resis-tive indexes and was started on ramipril at 5 mg/day. In 2015, her NVC switched to an active pattern of microangiopathy with fre-quent giant capillaries, frefre-quent capillary haemorrhages and a moderate capillary loss (Figures 1B) (5-7). The patient had no new digital ulcers.

The patient was put on cyclic intravenous iloprost for Raynaud’s phenomenon, but in 2016, she was no longer able to continue the therapy prescribed due to problems at her workplace. Therefore, aminaphtone (75 mg twice daily) was started off-label, in combination with her other treatment (bosentan, methotrexate and ramipril). Raynaud condition score, frequency and duration of Raynaud’s attacks and LAS-CA were performed at baseline (T0) and after four (T4) weeks of treatment, at the level of her hands to evaluate her clinical condition (Figure 3). Treatment with ami-naphtone improved the symptoms related to Raynaud’s phenomenon, and the blood perfusion in all skin areas improved rapidly (Figure 3, T4).

At time of writing the NVC status and or-gan involvement have not changed since 2015 and the patient has had no new digital ulcers since 2013.

Acknowledgements and Funding: the

authors would like to thank Barbara Wade, contract Professor at the University of To-rino, for her linguistic advice. Dr. Sara De

Figure 1 - Nailfoild videocapillaroscopic patterns of scleroderma

mi-croangiopathy (200x) in our patient (ME), showing an Early pattern in 2012 (A), and an Active pattern in 2015 (B).

Figure 2 - LASCA images (3rd_{finger) of active}

ulcer before (A) and after two months’ treat-ment (B), at the fingertip level. Scan image: blue = low blood perfusion (BP), yellow = in-termediate BP, red = high BP.

Figure 3 - LASCA images of the dorsum and

palm of the hand in our SSc patients before (T0) and at four weeks (T4) of treatment with Aminapthone. Perfusion is reported as perfu-sion units (PU). BP = blood perfuperfu-sion.

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LASCA images (3

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LASCA images (3

ulcer before (A) and after two months’ treat

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ulcer before (A) and after two months’ treat

ment (B), at the fingertip level. Scan image:

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ment (B), at the fingertip level. Scan image:

blue = low blood perfusion (BP), yellow = in

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blue = low blood perfusion (BP), yellow = in

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2016, she was no longer able to continue

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2016, she was no longer able to continue

the therapy prescribed due to problems at

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the therapy prescribed due to problems at

her workplace. Therefore, aminaphtone

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her workplace. Therefore, aminaphtone

(75 mg twice daily) was started off-label,

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(75 mg twice daily) was started off-label,

in combination with her other treatment

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in combination with her other treatment

(bosentan, methotrexate and ramipril).

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(bosentan, methotrexate and ramipril).

Raynaud condition score, frequency and

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Raynaud condition score, frequency and

duration of Raynaud’s attacks and LAS

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duration of Raynaud’s attacks and LAS

CA were performed at baseline (T0) and

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CA were performed at baseline (T0) and

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termediate BP, red = high BP.

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termediate BP, red = high BP.

use

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136 Reumatismo 3/2017

B. Ruaro, S. Paolino, C. Pizzorni, et al.

Gregorio from the Division of Rheumatol-ogy, University of Genova, supported the graphic reproduction. Teresa Cannavale, Health Professional of Rheumatology, per-formed DU medications. Barbara Ruaro is supported by a Grant from the Italian So-ciety of Rheumatology, obtained in 2015. All the authors are members of the EULAR Study Group on Microcirculation in Rheu-matic Diseases.

Conflict of interest: Maurizio Cutolo

received research grants from Actelion, BMS, Laboratori Baldacci and Sanofi-Aventis.

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