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Research Letter |

Laser-Speckle Contrast Imaging A Novel Method for Assessment of Cutaneous Blood Flow in Perniosis FREE

Anna E. Stanhewicz, MS1; Sara B. Ferguson, MD2; Rebecca S. Bruning, BS1; Lacy M. Alexander, PhD1
[+] Author Affiliations
1Department of Kinesiology, The Pennsylvania State University, University Park
2Penn State Hershey Medical Group, State College, Pennsylvania
JAMA Dermatol. 2014;150(6):658-660. doi:10.1001/jamadermatol.2013.7937.
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Published online

Perniosis is a local inflammatory disorder caused by prolonged exposure to nonfreezing cold.1 The pathogenesis of this disorder is not fully understood but is likely of microvascular origin.2

We describe a novel method to evaluate cutaneous blood blow in a typical patient with perniosis, a woman in her 20s who was referred to the dermatology clinic with a 10-day history of painful purple discoloration on her toes that began shortly after running in cold weather. She had no lesions on her fingers and no systemic symptoms except for fatigue. Her family history was negative for autoimmune disease. The results of a workup that included complete blood cell count, antinuclear antibody cryoglobulins, and cold agglutinins were negative except for a slightly decreased white blood cell count and 8% atypical lymphocytes, which later normalized. She was placed on a regimen of nifedipine (10 mg twice daily). Her skin symptoms resolved during 3 months but recurred when exposed to cold and when stopping nifedipine.

This study was approved by The Pennsylvania State University institutional review board. Both written consent and verbal consent were obtained from the participants. Measurements were obtained weekly for 4 weeks during the course of treatment. The protocol was repeated in a healthy age- and sex-matched individual.

The patient donned a water-perfused suit that covered the entire body3 and was instrumented with thermocouples on the dorsomedial, lateral, and mid-right foot for measurement of skin temperature. A laser Doppler flowmetry probe in a local heater was placed on the left foot in an area unaffected by ulcerations. Blood pressure was measured continuously throughout the protocol.

First, 33°C water was perfused through the suit for thermoneutral measurements, and then 48°C water was perfused to increase the mean skin temperature and stimulate cutaneous vasodilation. A laser-speckle contrast image (LSCI) (moorFLPI; Moor Instruments) was obtained of the right foot to visualize cutaneous blood flow throughout the protocol. The patient was returned to thermoneutral, and the local heater on the left foot was increased to 42°C to induce local endothelial nitric oxide synthase–dependent vasodilation.4 Laser Doppler flux under the local heater was measured throughout local heating. Cutaneous vascular conductance (CVC) was calculated as an index of skin blood flow using the following equation: CVC = Flux/MAP, where MAP indicates the mean arterial pressure.

Figure 1 shows an LSCI and the mean skin temperature of the right foot of a healthy control subject (left panels) and the patient with perniosis at baseline (middle panels) and following 4 weeks of nifedipine treatment (right panels) during thermoneutral (A) and warming (B) conditions. No appreciable differences were observed between the patient and the control subject at thermoneutral. The patient had reduced cutaneous vasodilation and lower skin temperature in her foot during warming. Figure 2 shows a representative tracing of cutaneous blood flow (CVC) response to local heating (A) and CVC data from the left foot of the control subject and the patient with perniosis at baseline and following 4 weeks of nifedipine treatment (B). The patient had a lower CVC response to local heating at baseline. The CVC responses were increased following 4 weeks of treatment.

Place holder to copy figure label and caption
Figure 1.
Laser-Speckle Contrast Images

Laser-speckle contrast images and the mean skin temperature (Tsk) of the right foot of a healthy control subject (left panels) and the patient with perniosis at baseline (middle panels) and following 4 weeks of nifedipine treatment (right panels) during thermoneutral (A) and whole-body warming (B) conditions. No appreciable differences in skin blood flow measured by laser-speckle contrast were observed between the patient and the control subject at thermoneutral. The patient had reduced cutaneous vasodilation and lower skin temperature in her foot during whole-body warming. Low blood flow and high blood flow are given as arbitrary perfusion units.

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Place holder to copy figure label and caption
Figure 2.
Cutaneous Blood Flow Response to Local Heating

Representative tracing of cutaneous blood flow (cutaneous vascular conductance [CVC]) response to local heating (A) and plateau in CVC due to local heat data from the left foot of a healthy control subject and the patient with perniosis at baseline and following 4 weeks of nifedipine treatment (B). The patient had a lower cutaneous vasodilation response to local heating at baseline. Cutaneous vasodilation responses were increased following 4 weeks of treatment. CVC is given as laser Doppler flux divided by the mean arterial pressure. Time is in minutes, with each hash mark on the x-axis representing 10 minutes.

Graphic Jump Location

This case highlights the LSCI as a novel method for assessment of cutaneous blood flow in patients with cold-related disorders. In the patient with perniosis, cutaneous blood flow of the foot assessed with an LSCI was reduced, and microvascular reactivity to an endothelial nitric oxide synthase–dependent stimulus was decreased. Quantitatively, these microvascular responses to systemic and localized heat stimuli normalized during nifedipine treatment.

Cutaneous vasodilation responses to heating stimuli have been used to assess microvascular function in the forearm skin of humans with varying preclinical vascular disease.5,6 The new, noninvasive LSCI technology presents the opportunity to comfortably and easily examine regional variation in cutaneous perfusion, rendering its clinical application in assessment of cutaneous vascular pathologic conditions. Further research is warranted to determine if an LSCI can predict the occurrence of ulcerations in patients with perniosis. Our data suggest that the LSCI can be used to examine cutaneous blood flow and to assess the efficacy of interventions in dermatology patients.

Corresponding Author: Lacy M. Alexander, PhD, Department of Kinesiology, The Pennsylvania State University, 113 Noll Laboratory, University Park, PA 16802 (lma191@psu.edu).

Accepted for Publication: August 27, 2013.

Published Online: March 12, 2014. doi:10.1001/jamadermatol.2013.7937.

Author Contributions: Ms Stanhewicz and Dr Alexander had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Stanhewicz, Bruning, Alexander.

Acquisition of data: Stanhewicz, Bruning.

Analysis and interpretation of data: All authors.

Drafting of the manuscript: All authors.

Clinical revision of the manuscript for important intellectual content: Stanhewicz, Ferguson, Alexander.

Administrative, technical, or material support: All authors.

Study supervision: All authors.

Conflict of Interest Disclosures: None reported.

Additional Contributions: Jane M. Pierzga, MS, Department of Kinesiology, The Pennsylvania State University, provided technical assistance. We thank the participants for their cooperation in this case study.

Prakash  S, Weisman  MH.  Idiopathic chilblains. Am J Med. 2009;122(12):1152-1155.
PubMed   |  Link to Article
Ozmen  M, Kurtoglu  V, Can  G, Tarhan  EF, Soysal  D, Aslan  SL.  The capillaroscopic findings in idiopathic pernio: is it a microvascular disease? Mod Rheumatol. 2013;23(5):897-903.
PubMed   |  Link to Article
Rowell  LB, Brengelmann  GL, Murray  JA.  Cardiovascular responses to sustained high skin temperature in resting man. J Appl Physiol. 1969;27(5):673-680.
PubMed
Bruning  RS, Santhanam  L, Stanhewicz  AE,  et al.  Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin. J Appl Physiol (1985). 2012;112(12):2019-2026.
PubMed   |  Link to Article
Smith  CJ, Santhanam  L, Bruning  RS, Stanhewicz  A, Berkowitz  DE, Holowatz  LA.  Upregulation of inducible nitric oxide synthase contributes to attenuated cutaneous vasodilation in essential hypertensive humans. Hypertension. 2011;58(5):935-942.
PubMed   |  Link to Article
Holowatz  LA, Kenney  WL.  Up-regulation of arginase activity contributes to attenuated reflex cutaneous vasodilatation in hypertensive humans. J Physiol. 2007;581(pt 2):863-872.
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.
Laser-Speckle Contrast Images

Laser-speckle contrast images and the mean skin temperature (Tsk) of the right foot of a healthy control subject (left panels) and the patient with perniosis at baseline (middle panels) and following 4 weeks of nifedipine treatment (right panels) during thermoneutral (A) and whole-body warming (B) conditions. No appreciable differences in skin blood flow measured by laser-speckle contrast were observed between the patient and the control subject at thermoneutral. The patient had reduced cutaneous vasodilation and lower skin temperature in her foot during whole-body warming. Low blood flow and high blood flow are given as arbitrary perfusion units.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Cutaneous Blood Flow Response to Local Heating

Representative tracing of cutaneous blood flow (cutaneous vascular conductance [CVC]) response to local heating (A) and plateau in CVC due to local heat data from the left foot of a healthy control subject and the patient with perniosis at baseline and following 4 weeks of nifedipine treatment (B). The patient had a lower cutaneous vasodilation response to local heating at baseline. Cutaneous vasodilation responses were increased following 4 weeks of treatment. CVC is given as laser Doppler flux divided by the mean arterial pressure. Time is in minutes, with each hash mark on the x-axis representing 10 minutes.

Graphic Jump Location

Tables

References

Prakash  S, Weisman  MH.  Idiopathic chilblains. Am J Med. 2009;122(12):1152-1155.
PubMed   |  Link to Article
Ozmen  M, Kurtoglu  V, Can  G, Tarhan  EF, Soysal  D, Aslan  SL.  The capillaroscopic findings in idiopathic pernio: is it a microvascular disease? Mod Rheumatol. 2013;23(5):897-903.
PubMed   |  Link to Article
Rowell  LB, Brengelmann  GL, Murray  JA.  Cardiovascular responses to sustained high skin temperature in resting man. J Appl Physiol. 1969;27(5):673-680.
PubMed
Bruning  RS, Santhanam  L, Stanhewicz  AE,  et al.  Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin. J Appl Physiol (1985). 2012;112(12):2019-2026.
PubMed   |  Link to Article
Smith  CJ, Santhanam  L, Bruning  RS, Stanhewicz  A, Berkowitz  DE, Holowatz  LA.  Upregulation of inducible nitric oxide synthase contributes to attenuated cutaneous vasodilation in essential hypertensive humans. Hypertension. 2011;58(5):935-942.
PubMed   |  Link to Article
Holowatz  LA, Kenney  WL.  Up-regulation of arginase activity contributes to attenuated reflex cutaneous vasodilatation in hypertensive humans. J Physiol. 2007;581(pt 2):863-872.
PubMed   |  Link to Article

Correspondence

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