Dermatologic Therapy, Vol. Vol.••, 28,2015, 2015,••–•• 279–281 Printed in the the United United States States · All All rights rightsreserved reserved
C 2015 Wiley Periodicals, Inc. V © 2015 Wiley Periodicals, Inc.
DERMATOLOGIC DERMATOLOGIC THERAPY THERAPY ISSN ISSN1396-0296 1396-0296
THERAPEUTIC HOTLINE Fractional photothermolysis treatment of digital cutis laxa reverses hand disability Jack J. Tian*, Wendy C. Hsiao† & Scott D. Worswick‡ *David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California †Keck School of Medicine, University of Southern California, Los Angeles, California ‡Division of Dermatology, Department of Medicine, University of California in Los Angeles, Los Angeles, California
ABSTRACT: In this case study, we present a safe and novel treatment for a patient with soft tissue hand disability caused by severe and chronic lupus and cutis laxa (CL). This patient was a woman in her 50s with a 20-year history of systemic lupus erythematous (SLE) and multiple sclerosis who developed hand disability because of the drastic loss of firmness in her soft tissue, extending from the dermis down to the ligaments. The likely cause was CL with SLE synovitis, exacerbated by corticosteroid tapering. Fractional photothermolysis (FP) LASER (Fraxel DUAL 1550/1927; Solta Medical) therapy profoundly alleviated her joint locking in addition to improving the firmness of the overlying skin to reverse her hand disability. This case illustrates a novel approach to CL hand treatment and the profound impact the treatment had on the patient’s disabled hand. FP therapy is quick and safe, and its medical application to skin and joints should be further explored. KEYWORDS: connective tissue disorders, cutis laxa, laser
Case report A woman in her 50s presented to the dermatology outpatient clinic complaining of being unable to grasp objects with her hands. The patient’s symptoms began 2 years ago and had progressively deteriorated over the past 6 months. The patient described the fingertips as soft, swollen, and proAddress correspondence and reprint requests to: Scott D. Worswick, MD, Assistant Clinical Professor of Dermatology and Director of Inpatient Dermatology, Division of Dermatology, Department of Medicine, University of California, Los Angeles, 200 Medical Plaza, Suite 450, Los Angeles CA 90095, or email: [email protected]. Portions of the case described in this manuscript were presented at the Rheumatologic Dermatology Society Annual Meeting; October 26, 2013, La Jolla, CA.
viding little traction, requiring her to wear gloves in order to pick up objects. She also described difficulty grasping because of joint locking in her fingers. The patient’s condition was severely debilitating such that she struggled to dress, eat, and turn doorknobs. The patient has a 20-year history of multiple sclerosis (MS) and systemic lupus erythematosus (SLE). She was initially treated with high-dose oral prednisone but had begun a prednisone taper 6 months prior to her presentation to the dermatology clinic (as she concurrently started another immune modulator, belimumab). At the time of presentation, her oral prednisone dose had been tapered, and by her final LASER treatment (described below), the patient was no longer taking oral prednisone. To control her SLE, the patient was additionally being treated with three other
279 1
al. Tian et al.
immunomodulatory drugs: oral hydroxychloroquine 200 mg twice daily, oral azathioprine 100 mg twice daily, and intravenous belimumab at 10 mg/kg every 4 weeks. On physical examination, she exhibited skin laxity most prominent in both hands, under her eyes, and on her feet. Her fingertips were soft and edematous such that the contour of her first metacarpal could be distinctly palpated. Following tenting the webbing of her thenar space, her skin fold remained tented for over 40 seconds, showing drastic loss of elasticity (Fig. 1). Her fingertips failed to provide enough traction to form a good grasp, and her locking phalangeal joints exacerbated her difficulty with gripping. Our initial assessment was that the loose structure of her dermis and soft tissue led to joint misalignment and contributed to the locking of her joints. A right thumb 4-mm punch biopsy was performed. Hematoxylin and eosin stain showed focal dermal fibrosis. A Verhoeff–Van Gieson stain was positive and highlighted the patchy loss and fragmentation of elastic fibers in the dermis. Direct immunofluorescence showed linear immunoglobulin A (IgA) at the dermal-epidermal junction (DEJ). The histological features were compatible with the clinical impression of cutis laxa (CL). The current clinical management of CL includes surgical excision of the lax skin, botulinum toxin (BoTox) injections, and most recently, fractional photothermolysis (FP) skin tightening. However,
these indications are generally for the face (1). We elected to treat our patient’s hands with FP because of the invasive nature of surgery and the transience of BoTox. The patient received four once-monthly courses of FP treatments. For each course, we used the Fraxel DUAL 1550/1927 LASER (Solta Medical, Hayward, CA) at 1550 nm, 60 mJ at a treatment level of 8 for 8 passes. Because of the pain induced by FP, we used topical lidocaine/prilocaine followed by nerve blocks with 1% lidocaine solution. One month after the first treatment of the anterior right thumb and index finger, the patient noted drastic improvement in the firmness of her skin, especially when compared with the skin of adjacent, untreated digits; moreover, her right thumb and index finger joints no longer locked. During the second treatment, we treated the first three fingers of her right hand; the third, her entire right hand; and the fourth, her entire left hand. Again, major improvements were made in skin firmness and there was less joint locking in all treated digits. At this point (4 months after the initial course of treatment), the patient had regained complete functionality in her right hand. Three months after completion of treatment to her right hand, her skin laxity was still 50% improved compared with pretreatment, but had begun to recur. Her joints remained unlocked (Fig. 2).
Discussion
FIG. 1. Right hand before fractional photothermolysis treatment.Visible from this pretreatment photograph is the persistent tenting of the patient’s thenar eminence and index finger 20 seconds after the skin had been pinched.
280 2
Acquired CL is associated with connective tissue diseases such as SLE and rheumatoid arthritis (1). Our patient’s late onset of CL, her diagnosis of MS and SLE, and the abundance of linear IgA at the DEJ suggest her CL is acquired and autoimmune. IgA is normally secreted in mucous lining membranes, and its abundance in the DEJ suggests immune dysfunction such as in dermatitis herpetiformis or adult linear IgA disease, where the IgA-circulating immune complexes deposit in the DEJ or when the IgA reacts to DEJ epitopes (2). We speculate that our patient increased secretion of IgA upon prednisone tapering and that this perhaps down-regulated the dermal fibroblast from producing elastin, causing her CL symptoms. The inarticulating joints may be a sequela of SLE and are often diagnosed as SLE synovitis, osteonecrosis, or osteochondritis desiccans (OCD) (3). In osteonecrosis and OCD, small vessels are damaged resulting in ischemia to bone or cartilage, respectively. Corticosteroid tapering commonly exacerbates this because of the formation of fat
Fractional Fractionalphotothermolysis photothermolysis for for digital digital cutis cutis laxa
FIG. 2. Right hand 3 months after completion of fractional photothermolysis treatment. After completion of fractional photothermolysis treatment of the right hand, the skin turgor had improved on all treated areas.
emboli (3). Furthermore, acquired CL can decrease or disrupt elastin to cause small vessel damage consistent with vasculitis. She was prescribed immune modulating drugs (hydroxychloroquine, azathioprine, prednisone, belimumab), but they were ineffective in relieving her CL symptoms. We elected to treat our patient with FP as a less invasive, potentially longer lasting, and in the long term more economical alternative to the currently available CL therapies. FP causes injury through small columns of skin interspersed with uninjured columns. The injured columns undergo fibroplasia and remodeling with the aid of fibroblasts from uninjured areas, resulting in an increase of new dermal collagen and elastin (4,5). Within the first month of FP treatment, her skin turgor had improved on all areas treated (right anterior index finger and thumb), and this trend continued following treatment of the remaining digits of her right hand. Remarkably, the patient also experienced a decrease in joint locking following FP. The allevia-
tion of her joint locking prompted several theories. The first hypothesis is that FP stimulated fibroblasts to proliferate and remodel the dermis. Evidence of increased production of tropoelastin and total elastin has been shown in recent FP trials (5). As a result, the increased skin turgor and dermal firmness facilitated the patient’s grip and allowed her joints to better align. Another hypothesis is that FP generates radical oxygen species (ROS) from water molecules by excessively increasing the internal energy within the -OH bond (6). Generated ROS molecules spill over into deeper tissues (subdermal layers), stimulating fibroblasts residing in ligaments, cartilage, and bone. The activated and proliferating fibroblasts consequently remodeled the deeper connective tissues to alleviate the patient’s joint locking. Some skin laxity recurring while the joint articulation has maintained its improvement suggests that the LASER affects the joints in addition to the skin. This case illustrates a novel approach to CL hand treatment and the profound impact the treatment had on the patient’s disabled hand. FP therapy is quick and safe, and its medical application to skin and joints should be further explored.
Conflicts of interest No conflicts of interest to disclose.
References 1. Berk DR, Bentley DD, Bayliss SJ, et al. Cutis laxa: a review. J Am Acad Dermatol 2012: 66: e1–e17. 2. Hall RP, Lawley TJ. Characterization of circulating and cutaneous IgA immune complexes in patients with dermatitis herpetiformis. J Immunol 1985: 135: 1760–1765. 3. Lightfoot RW Jr, Lotke PA. Osteonecrosis of metacarpal heads in systemic lupus erythematosus. Value of radiostrontium scintimetry in differential diagnosis. Arthritis Rheum 1972: 15: 486–492. 4. Gold MH. Update on fractional laser technology. J Clin Aesthet Dermatol 2010: 3: 42–50. 5. El-Domyati M, El-Ammawi TS, Medhat W, et al. Multiple minimally invasive erbium: yttrium aluminum garnet laser mini-peels for skin rejuvenation: an objective assessment. J Cosmet Dermatol 2012: 11: 122–130. 6. Lubart R, Friedmann H, Lavie R, Baruchin AM. A novel explanation for the healing effect of the Er:YAG laser during skin rejuvenation. J Cosmet Laser Ther 2010: 12: 256–257.
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C 2015 Wiley Periodicals, Inc. V © 2015 Wiley Periodicals, Inc.
DERMATOLOGIC DERMATOLOGIC THERAPY THERAPY ISSN ISSN1396-0296 1396-0296
THERAPEUTIC HOTLINE Fractional photothermolysis treatment of digital cutis laxa reverses hand disability Jack J. Tian*, Wendy C. Hsiao† & Scott D. Worswick‡ *David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California †Keck School of Medicine, University of Southern California, Los Angeles, California ‡Division of Dermatology, Department of Medicine, University of California in Los Angeles, Los Angeles, California
ABSTRACT: In this case study, we present a safe and novel treatment for a patient with soft tissue hand disability caused by severe and chronic lupus and cutis laxa (CL). This patient was a woman in her 50s with a 20-year history of systemic lupus erythematous (SLE) and multiple sclerosis who developed hand disability because of the drastic loss of firmness in her soft tissue, extending from the dermis down to the ligaments. The likely cause was CL with SLE synovitis, exacerbated by corticosteroid tapering. Fractional photothermolysis (FP) LASER (Fraxel DUAL 1550/1927; Solta Medical) therapy profoundly alleviated her joint locking in addition to improving the firmness of the overlying skin to reverse her hand disability. This case illustrates a novel approach to CL hand treatment and the profound impact the treatment had on the patient’s disabled hand. FP therapy is quick and safe, and its medical application to skin and joints should be further explored. KEYWORDS: connective tissue disorders, cutis laxa, laser
Case report A woman in her 50s presented to the dermatology outpatient clinic complaining of being unable to grasp objects with her hands. The patient’s symptoms began 2 years ago and had progressively deteriorated over the past 6 months. The patient described the fingertips as soft, swollen, and proAddress correspondence and reprint requests to: Scott D. Worswick, MD, Assistant Clinical Professor of Dermatology and Director of Inpatient Dermatology, Division of Dermatology, Department of Medicine, University of California, Los Angeles, 200 Medical Plaza, Suite 450, Los Angeles CA 90095, or email: [email protected]. Portions of the case described in this manuscript were presented at the Rheumatologic Dermatology Society Annual Meeting; October 26, 2013, La Jolla, CA.
viding little traction, requiring her to wear gloves in order to pick up objects. She also described difficulty grasping because of joint locking in her fingers. The patient’s condition was severely debilitating such that she struggled to dress, eat, and turn doorknobs. The patient has a 20-year history of multiple sclerosis (MS) and systemic lupus erythematosus (SLE). She was initially treated with high-dose oral prednisone but had begun a prednisone taper 6 months prior to her presentation to the dermatology clinic (as she concurrently started another immune modulator, belimumab). At the time of presentation, her oral prednisone dose had been tapered, and by her final LASER treatment (described below), the patient was no longer taking oral prednisone. To control her SLE, the patient was additionally being treated with three other
279 1
al. Tian et al.
immunomodulatory drugs: oral hydroxychloroquine 200 mg twice daily, oral azathioprine 100 mg twice daily, and intravenous belimumab at 10 mg/kg every 4 weeks. On physical examination, she exhibited skin laxity most prominent in both hands, under her eyes, and on her feet. Her fingertips were soft and edematous such that the contour of her first metacarpal could be distinctly palpated. Following tenting the webbing of her thenar space, her skin fold remained tented for over 40 seconds, showing drastic loss of elasticity (Fig. 1). Her fingertips failed to provide enough traction to form a good grasp, and her locking phalangeal joints exacerbated her difficulty with gripping. Our initial assessment was that the loose structure of her dermis and soft tissue led to joint misalignment and contributed to the locking of her joints. A right thumb 4-mm punch biopsy was performed. Hematoxylin and eosin stain showed focal dermal fibrosis. A Verhoeff–Van Gieson stain was positive and highlighted the patchy loss and fragmentation of elastic fibers in the dermis. Direct immunofluorescence showed linear immunoglobulin A (IgA) at the dermal-epidermal junction (DEJ). The histological features were compatible with the clinical impression of cutis laxa (CL). The current clinical management of CL includes surgical excision of the lax skin, botulinum toxin (BoTox) injections, and most recently, fractional photothermolysis (FP) skin tightening. However,
these indications are generally for the face (1). We elected to treat our patient’s hands with FP because of the invasive nature of surgery and the transience of BoTox. The patient received four once-monthly courses of FP treatments. For each course, we used the Fraxel DUAL 1550/1927 LASER (Solta Medical, Hayward, CA) at 1550 nm, 60 mJ at a treatment level of 8 for 8 passes. Because of the pain induced by FP, we used topical lidocaine/prilocaine followed by nerve blocks with 1% lidocaine solution. One month after the first treatment of the anterior right thumb and index finger, the patient noted drastic improvement in the firmness of her skin, especially when compared with the skin of adjacent, untreated digits; moreover, her right thumb and index finger joints no longer locked. During the second treatment, we treated the first three fingers of her right hand; the third, her entire right hand; and the fourth, her entire left hand. Again, major improvements were made in skin firmness and there was less joint locking in all treated digits. At this point (4 months after the initial course of treatment), the patient had regained complete functionality in her right hand. Three months after completion of treatment to her right hand, her skin laxity was still 50% improved compared with pretreatment, but had begun to recur. Her joints remained unlocked (Fig. 2).
Discussion
FIG. 1. Right hand before fractional photothermolysis treatment.Visible from this pretreatment photograph is the persistent tenting of the patient’s thenar eminence and index finger 20 seconds after the skin had been pinched.
280 2
Acquired CL is associated with connective tissue diseases such as SLE and rheumatoid arthritis (1). Our patient’s late onset of CL, her diagnosis of MS and SLE, and the abundance of linear IgA at the DEJ suggest her CL is acquired and autoimmune. IgA is normally secreted in mucous lining membranes, and its abundance in the DEJ suggests immune dysfunction such as in dermatitis herpetiformis or adult linear IgA disease, where the IgA-circulating immune complexes deposit in the DEJ or when the IgA reacts to DEJ epitopes (2). We speculate that our patient increased secretion of IgA upon prednisone tapering and that this perhaps down-regulated the dermal fibroblast from producing elastin, causing her CL symptoms. The inarticulating joints may be a sequela of SLE and are often diagnosed as SLE synovitis, osteonecrosis, or osteochondritis desiccans (OCD) (3). In osteonecrosis and OCD, small vessels are damaged resulting in ischemia to bone or cartilage, respectively. Corticosteroid tapering commonly exacerbates this because of the formation of fat
Fractional Fractionalphotothermolysis photothermolysis for for digital digital cutis cutis laxa
FIG. 2. Right hand 3 months after completion of fractional photothermolysis treatment. After completion of fractional photothermolysis treatment of the right hand, the skin turgor had improved on all treated areas.
emboli (3). Furthermore, acquired CL can decrease or disrupt elastin to cause small vessel damage consistent with vasculitis. She was prescribed immune modulating drugs (hydroxychloroquine, azathioprine, prednisone, belimumab), but they were ineffective in relieving her CL symptoms. We elected to treat our patient with FP as a less invasive, potentially longer lasting, and in the long term more economical alternative to the currently available CL therapies. FP causes injury through small columns of skin interspersed with uninjured columns. The injured columns undergo fibroplasia and remodeling with the aid of fibroblasts from uninjured areas, resulting in an increase of new dermal collagen and elastin (4,5). Within the first month of FP treatment, her skin turgor had improved on all areas treated (right anterior index finger and thumb), and this trend continued following treatment of the remaining digits of her right hand. Remarkably, the patient also experienced a decrease in joint locking following FP. The allevia-
tion of her joint locking prompted several theories. The first hypothesis is that FP stimulated fibroblasts to proliferate and remodel the dermis. Evidence of increased production of tropoelastin and total elastin has been shown in recent FP trials (5). As a result, the increased skin turgor and dermal firmness facilitated the patient’s grip and allowed her joints to better align. Another hypothesis is that FP generates radical oxygen species (ROS) from water molecules by excessively increasing the internal energy within the -OH bond (6). Generated ROS molecules spill over into deeper tissues (subdermal layers), stimulating fibroblasts residing in ligaments, cartilage, and bone. The activated and proliferating fibroblasts consequently remodeled the deeper connective tissues to alleviate the patient’s joint locking. Some skin laxity recurring while the joint articulation has maintained its improvement suggests that the LASER affects the joints in addition to the skin. This case illustrates a novel approach to CL hand treatment and the profound impact the treatment had on the patient’s disabled hand. FP therapy is quick and safe, and its medical application to skin and joints should be further explored.
Conflicts of interest No conflicts of interest to disclose.
References 1. Berk DR, Bentley DD, Bayliss SJ, et al. Cutis laxa: a review. J Am Acad Dermatol 2012: 66: e1–e17. 2. Hall RP, Lawley TJ. Characterization of circulating and cutaneous IgA immune complexes in patients with dermatitis herpetiformis. J Immunol 1985: 135: 1760–1765. 3. Lightfoot RW Jr, Lotke PA. Osteonecrosis of metacarpal heads in systemic lupus erythematosus. Value of radiostrontium scintimetry in differential diagnosis. Arthritis Rheum 1972: 15: 486–492. 4. Gold MH. Update on fractional laser technology. J Clin Aesthet Dermatol 2010: 3: 42–50. 5. El-Domyati M, El-Ammawi TS, Medhat W, et al. Multiple minimally invasive erbium: yttrium aluminum garnet laser mini-peels for skin rejuvenation: an objective assessment. J Cosmet Dermatol 2012: 11: 122–130. 6. Lubart R, Friedmann H, Lavie R, Baruchin AM. A novel explanation for the healing effect of the Er:YAG laser during skin rejuvenation. J Cosmet Laser Ther 2010: 12: 256–257.
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