The 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria showed accuracy similar to that of the 2010 McDonald criteria in predicting the development of clinically definite multiple sclerosis, a retrospective study found.

“Among the different modifications proposed, our results support removal of the distinction between symptomatic and asymptomatic lesions, which simplifies the clinical use of MRI criteria, and suggest that further consideration is given to increasing the number of lesions needed to define periventricular involvement from one to three, because this might slightly increase specificity,” wrote researchers led by Massimo Filippi, MD. The report was published Dec. 21, 2017, in The Lancet Neurology. “Further effort is still needed to improve cortical lesion assessment and more studies should be done to evaluate the effect of including optic nerve assessment as an additional DIS [dissemination in space] criterion.”

solitude72/iStockphoto

[email protected]

SOURCE: Filippi M et al., Lancet Neurol. 2017 Dec 21. doi: 10.1016/S1474-4422(17)30469-6.

The 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria showed accuracy similar to that of the 2010 McDonald criteria in predicting the development of clinically definite multiple sclerosis, a retrospective study found.

“Among the different modifications proposed, our results support removal of the distinction between symptomatic and asymptomatic lesions, which simplifies the clinical use of MRI criteria, and suggest that further consideration is given to increasing the number of lesions needed to define periventricular involvement from one to three, because this might slightly increase specificity,” wrote researchers led by Massimo Filippi, MD. The report was published Dec. 21, 2017, in The Lancet Neurology. “Further effort is still needed to improve cortical lesion assessment and more studies should be done to evaluate the effect of including optic nerve assessment as an additional DIS [dissemination in space] criterion.”

solitude72/iStockphoto

[email protected]

SOURCE: Filippi M et al., Lancet Neurol. 2017 Dec 21. doi: 10.1016/S1474-4422(17)30469-6.

The 2016 Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) criteria showed accuracy similar to that of the 2010 McDonald criteria in predicting the development of clinically definite multiple sclerosis, a retrospective study found.

“Among the different modifications proposed, our results support removal of the distinction between symptomatic and asymptomatic lesions, which simplifies the clinical use of MRI criteria, and suggest that further consideration is given to increasing the number of lesions needed to define periventricular involvement from one to three, because this might slightly increase specificity,” wrote researchers led by Massimo Filippi, MD. The report was published Dec. 21, 2017, in The Lancet Neurology. “Further effort is still needed to improve cortical lesion assessment and more studies should be done to evaluate the effect of including optic nerve assessment as an additional DIS [dissemination in space] criterion.”

solitude72/iStockphoto

[email protected]

SOURCE: Filippi M et al., Lancet Neurol. 2017 Dec 21. doi: 10.1016/S1474-4422(17)30469-6.

Dermoscopy increases diagnostic accuracy in the analysis of skin growths.^1,2 Recently the use of dermoscopy has broadened to include inflammatory dermatoses and skin infections.³ To substantiate the value of dermoscopy in assessing psoriasis, we performed a systematic review of the literature and briefly reviewed 31 articles. We also report a case that highlights the differences between psoriasis and basal cell carcinoma (BCC) under dermoscopic examination, and we discuss the literature on the dermoscopic findings of psoriasis with an emphasis on the relative sensitivities and specificities of dermoscopic findings for psoriasis and for BCC.

Case Report

A 63-year-old man with psoriasis and a history of BCC presented for follow-up of psoriasis, which was well-controlled on etanercept. The physical examination was remarkable for scaly pink papules scattered on the trunk and extremities. A new larger red-pink patch was located on the left lower back (Figure 1). Dermoscopic evaluation of the new patch revealed shiny white lines and branching blood vessels (Figure 2). Pathology results of a shave biopsy revealed superficial BCC. The skin cancer was treated with electrodesiccation and curettage.

Comment

The clinical morphology of psoriasis and BCC can be similar, and dermoscopy can help in differentiating between the 2 conditions.

Literature Search on Dermoscopy and Psoriasis
We performed a PubMed search of articles indexed for MEDLINE to review the published literature on dermoscopy and psoriasis. Two reviewers (C.H. and L.C.) searched for psoriasis paired with the terms dermoscopy or dermatoscopy or epiluminescence microscopy. Only English-language articles published between 1996 and 2016 were included in the search. Articles that focused solely on confocal microscopy were excluded. Article titles and abstracts were evaluated and articles that omitted mention of dermoscopy and psoriasis were excluded, yielding a total of 31 articles. Of these articles, only 2 discussed the specificity or sensitivity of the dermoscopic findings of psoriasis.^4,5 Most of the articles were case reports and descriptive cross-sectional studies. The reports addressed multiple subtypes of psoriasis, but reports on psoriasis vulgaris and scalp psoriasis were most common (Table). Lallas et al⁶ provided a comprehensive descriptive review of the main findings on dermoscopy for psoriasis and other inflammatory skin conditions, but it lacked a comparison between psoriasis and BCC or data on the sensitivity and specificity of the findings. Two studies reported sensitivity and specificity values for the dermoscopic findings of psoriasis.^4,5 Pan et al⁵ reported a 98% diagnostic probability of psoriasis if red dots, homogeneous vascular pattern, and a light red background are all present. Additionally, they reported that the presence of 4 of 6 criteria for BCC—scattered vascular pattern, arborizing microvessels, telangiectatic or atypical vessels, milky-pink background, and brown dots⁄globules—yielded a diagnostic probability of 99%.⁵ Similarly, Lallas et al⁶ demonstrated that the presence of dotted vessels alone is not sufficient to presume a diagnosis of psoriasis, as this finding can be seen in other inflammatory skin conditions. However, “the combination of regularly distributed dotted vessels over a light red background associated with diffuse white scales was highly predictive of [plaque psoriasis] and allowed a correct diagnosis with 88.0% specificity and 84.9% sensitivity.”⁴ Figure 3 shows a dermoscopic image of plaque psoriasis that demonstrates these findings. The remaining literature corroborated this evidence, with the most commonly reported dermoscopic findings of psoriasis being red dots, red globules, glomerular vessels (also known as twisted capillary loops), red globular rings, and white scale.^7-12

Dermoscopy and BCC
Much has been published on the dermoscopic findings of BCC.^5,13-15 The dermoscopic findings of BCC include large blue-gray ovoid nests, leaflike areas, spoke-wheel–like areas, arborizing vessels (telangiectasia), and ulceration.¹⁵ Superficial BCC is characterized by short fine or arborizing telangiectasia, shallow erosions, and shiny white areas.¹⁵ The positive predictive value of dermoscopy in BCC is as high as 97%.¹⁶ Additionally, multiple studies report a sensitivity of 95% to 99%^5,13,14 and a specificity of 79% to 99% in the use of dermoscopy for identifying BCC. According to Pan et al,⁵ the most sensitive finding for BCC is a scattered vascular pattern (97%), while the most specific finding is arborizing microvessels (99%).

Utility of Dermoscopy
Our case of a 63-year-old man with a history of psoriasis and BCC highlights the usefulness of dermoscopy in accurately determining the features of each condition. Additionally, dermoscopy aids in differentiating between psoriasis and squamous cell carcinoma. In contrast to the dotted vessels seen in psoriasis, squamous cell carcinomas often have peripheral hairpin (glomerular) vessels.¹⁷

If future reports confirm dermoscopy’s utility in accurately diagnosing psoriasis, fewer biopsies may be needed when evaluating patients with new rashes. Furthermore, dermoscopy may expedite treatment of psoriasis (as it can for malignant conditions) by obviating the wait for pathology results currently needed to initiate systemic treatment. For patients with psoriasis who also have sun-damaged skin, dermoscopy may assist in differentiating pink patches and plaques of psoriasis from skin cancer, such as superficial BCCs, which often have shiny white lines not seen in psoriasis.¹⁵

Dermoscopy increases diagnostic accuracy in the analysis of skin growths.^1,2 Recently the use of dermoscopy has broadened to include inflammatory dermatoses and skin infections.³ To substantiate the value of dermoscopy in assessing psoriasis, we performed a systematic review of the literature and briefly reviewed 31 articles. We also report a case that highlights the differences between psoriasis and basal cell carcinoma (BCC) under dermoscopic examination, and we discuss the literature on the dermoscopic findings of psoriasis with an emphasis on the relative sensitivities and specificities of dermoscopic findings for psoriasis and for BCC.

Case Report

A 63-year-old man with psoriasis and a history of BCC presented for follow-up of psoriasis, which was well-controlled on etanercept. The physical examination was remarkable for scaly pink papules scattered on the trunk and extremities. A new larger red-pink patch was located on the left lower back (Figure 1). Dermoscopic evaluation of the new patch revealed shiny white lines and branching blood vessels (Figure 2). Pathology results of a shave biopsy revealed superficial BCC. The skin cancer was treated with electrodesiccation and curettage.

Comment

The clinical morphology of psoriasis and BCC can be similar, and dermoscopy can help in differentiating between the 2 conditions.

Literature Search on Dermoscopy and Psoriasis
We performed a PubMed search of articles indexed for MEDLINE to review the published literature on dermoscopy and psoriasis. Two reviewers (C.H. and L.C.) searched for psoriasis paired with the terms dermoscopy or dermatoscopy or epiluminescence microscopy. Only English-language articles published between 1996 and 2016 were included in the search. Articles that focused solely on confocal microscopy were excluded. Article titles and abstracts were evaluated and articles that omitted mention of dermoscopy and psoriasis were excluded, yielding a total of 31 articles. Of these articles, only 2 discussed the specificity or sensitivity of the dermoscopic findings of psoriasis.^4,5 Most of the articles were case reports and descriptive cross-sectional studies. The reports addressed multiple subtypes of psoriasis, but reports on psoriasis vulgaris and scalp psoriasis were most common (Table). Lallas et al⁶ provided a comprehensive descriptive review of the main findings on dermoscopy for psoriasis and other inflammatory skin conditions, but it lacked a comparison between psoriasis and BCC or data on the sensitivity and specificity of the findings. Two studies reported sensitivity and specificity values for the dermoscopic findings of psoriasis.^4,5 Pan et al⁵ reported a 98% diagnostic probability of psoriasis if red dots, homogeneous vascular pattern, and a light red background are all present. Additionally, they reported that the presence of 4 of 6 criteria for BCC—scattered vascular pattern, arborizing microvessels, telangiectatic or atypical vessels, milky-pink background, and brown dots⁄globules—yielded a diagnostic probability of 99%.⁵ Similarly, Lallas et al⁶ demonstrated that the presence of dotted vessels alone is not sufficient to presume a diagnosis of psoriasis, as this finding can be seen in other inflammatory skin conditions. However, “the combination of regularly distributed dotted vessels over a light red background associated with diffuse white scales was highly predictive of [plaque psoriasis] and allowed a correct diagnosis with 88.0% specificity and 84.9% sensitivity.”⁴ Figure 3 shows a dermoscopic image of plaque psoriasis that demonstrates these findings. The remaining literature corroborated this evidence, with the most commonly reported dermoscopic findings of psoriasis being red dots, red globules, glomerular vessels (also known as twisted capillary loops), red globular rings, and white scale.^7-12

Dermoscopy and BCC
Much has been published on the dermoscopic findings of BCC.^5,13-15 The dermoscopic findings of BCC include large blue-gray ovoid nests, leaflike areas, spoke-wheel–like areas, arborizing vessels (telangiectasia), and ulceration.¹⁵ Superficial BCC is characterized by short fine or arborizing telangiectasia, shallow erosions, and shiny white areas.¹⁵ The positive predictive value of dermoscopy in BCC is as high as 97%.¹⁶ Additionally, multiple studies report a sensitivity of 95% to 99%^5,13,14 and a specificity of 79% to 99% in the use of dermoscopy for identifying BCC. According to Pan et al,⁵ the most sensitive finding for BCC is a scattered vascular pattern (97%), while the most specific finding is arborizing microvessels (99%).

Utility of Dermoscopy
Our case of a 63-year-old man with a history of psoriasis and BCC highlights the usefulness of dermoscopy in accurately determining the features of each condition. Additionally, dermoscopy aids in differentiating between psoriasis and squamous cell carcinoma. In contrast to the dotted vessels seen in psoriasis, squamous cell carcinomas often have peripheral hairpin (glomerular) vessels.¹⁷

If future reports confirm dermoscopy’s utility in accurately diagnosing psoriasis, fewer biopsies may be needed when evaluating patients with new rashes. Furthermore, dermoscopy may expedite treatment of psoriasis (as it can for malignant conditions) by obviating the wait for pathology results currently needed to initiate systemic treatment. For patients with psoriasis who also have sun-damaged skin, dermoscopy may assist in differentiating pink patches and plaques of psoriasis from skin cancer, such as superficial BCCs, which often have shiny white lines not seen in psoriasis.¹⁵

Dermoscopy increases diagnostic accuracy in the analysis of skin growths.^1,2 Recently the use of dermoscopy has broadened to include inflammatory dermatoses and skin infections.³ To substantiate the value of dermoscopy in assessing psoriasis, we performed a systematic review of the literature and briefly reviewed 31 articles. We also report a case that highlights the differences between psoriasis and basal cell carcinoma (BCC) under dermoscopic examination, and we discuss the literature on the dermoscopic findings of psoriasis with an emphasis on the relative sensitivities and specificities of dermoscopic findings for psoriasis and for BCC.

Case Report

A 63-year-old man with psoriasis and a history of BCC presented for follow-up of psoriasis, which was well-controlled on etanercept. The physical examination was remarkable for scaly pink papules scattered on the trunk and extremities. A new larger red-pink patch was located on the left lower back (Figure 1). Dermoscopic evaluation of the new patch revealed shiny white lines and branching blood vessels (Figure 2). Pathology results of a shave biopsy revealed superficial BCC. The skin cancer was treated with electrodesiccation and curettage.

Comment

The clinical morphology of psoriasis and BCC can be similar, and dermoscopy can help in differentiating between the 2 conditions.

Literature Search on Dermoscopy and Psoriasis
We performed a PubMed search of articles indexed for MEDLINE to review the published literature on dermoscopy and psoriasis. Two reviewers (C.H. and L.C.) searched for psoriasis paired with the terms dermoscopy or dermatoscopy or epiluminescence microscopy. Only English-language articles published between 1996 and 2016 were included in the search. Articles that focused solely on confocal microscopy were excluded. Article titles and abstracts were evaluated and articles that omitted mention of dermoscopy and psoriasis were excluded, yielding a total of 31 articles. Of these articles, only 2 discussed the specificity or sensitivity of the dermoscopic findings of psoriasis.^4,5 Most of the articles were case reports and descriptive cross-sectional studies. The reports addressed multiple subtypes of psoriasis, but reports on psoriasis vulgaris and scalp psoriasis were most common (Table). Lallas et al⁶ provided a comprehensive descriptive review of the main findings on dermoscopy for psoriasis and other inflammatory skin conditions, but it lacked a comparison between psoriasis and BCC or data on the sensitivity and specificity of the findings. Two studies reported sensitivity and specificity values for the dermoscopic findings of psoriasis.^4,5 Pan et al⁵ reported a 98% diagnostic probability of psoriasis if red dots, homogeneous vascular pattern, and a light red background are all present. Additionally, they reported that the presence of 4 of 6 criteria for BCC—scattered vascular pattern, arborizing microvessels, telangiectatic or atypical vessels, milky-pink background, and brown dots⁄globules—yielded a diagnostic probability of 99%.⁵ Similarly, Lallas et al⁶ demonstrated that the presence of dotted vessels alone is not sufficient to presume a diagnosis of psoriasis, as this finding can be seen in other inflammatory skin conditions. However, “the combination of regularly distributed dotted vessels over a light red background associated with diffuse white scales was highly predictive of [plaque psoriasis] and allowed a correct diagnosis with 88.0% specificity and 84.9% sensitivity.”⁴ Figure 3 shows a dermoscopic image of plaque psoriasis that demonstrates these findings. The remaining literature corroborated this evidence, with the most commonly reported dermoscopic findings of psoriasis being red dots, red globules, glomerular vessels (also known as twisted capillary loops), red globular rings, and white scale.^7-12

Dermoscopy and BCC
Much has been published on the dermoscopic findings of BCC.^5,13-15 The dermoscopic findings of BCC include large blue-gray ovoid nests, leaflike areas, spoke-wheel–like areas, arborizing vessels (telangiectasia), and ulceration.¹⁵ Superficial BCC is characterized by short fine or arborizing telangiectasia, shallow erosions, and shiny white areas.¹⁵ The positive predictive value of dermoscopy in BCC is as high as 97%.¹⁶ Additionally, multiple studies report a sensitivity of 95% to 99%^5,13,14 and a specificity of 79% to 99% in the use of dermoscopy for identifying BCC. According to Pan et al,⁵ the most sensitive finding for BCC is a scattered vascular pattern (97%), while the most specific finding is arborizing microvessels (99%).

Utility of Dermoscopy
Our case of a 63-year-old man with a history of psoriasis and BCC highlights the usefulness of dermoscopy in accurately determining the features of each condition. Additionally, dermoscopy aids in differentiating between psoriasis and squamous cell carcinoma. In contrast to the dotted vessels seen in psoriasis, squamous cell carcinomas often have peripheral hairpin (glomerular) vessels.¹⁷

If future reports confirm dermoscopy’s utility in accurately diagnosing psoriasis, fewer biopsies may be needed when evaluating patients with new rashes. Furthermore, dermoscopy may expedite treatment of psoriasis (as it can for malignant conditions) by obviating the wait for pathology results currently needed to initiate systemic treatment. For patients with psoriasis who also have sun-damaged skin, dermoscopy may assist in differentiating pink patches and plaques of psoriasis from skin cancer, such as superficial BCCs, which often have shiny white lines not seen in psoriasis.¹⁵

The Diagnosis: Necrobiotic Xanthogranuloma

A 4-mm punch biopsy was performed for routine stain with hematoxylin and eosin. The differential diagnosis included sarcoidosis, necrobiosis lipoidica, xanthoma disseminatum, and multicentric reticulohistiocytosis. Histopathologic examination demonstrated a dermal infiltrate of foamy histiocytes and neutrophils (Figure). There were surrounding areas of degenerated collagen containing numerous cholesterol clefts. After clinical pathologic correlation, a diagnosis of necrobiotic xanthogranuloma (NXG) was elucidated.

The patient was referred to general surgery for elective excision of 1 or more of the lesions. Excision of an abdominal lesion was performed without complication. After several months, a new lesion reformed within the excisional scar that also was consistent with NXG. At further dermatologic visits, a trial of intralesional corticosteroids was attempted to the largest lesions with modest improvement. In addition, follow-up with hematology and oncology was recommended for routine surveillance of the known blood dyscrasia.

Necrobiotic xanthogranuloma is a multisystem non-Langerhans cell histiocytic disease. Clinically, NXG is characterized by infiltrative plaques and ulcerative nodules. Lesions may appear red, brown, or yellow with associated atrophy and telangiectasia.¹ Koch et al² described a predilection for granuloma formation within preexisting scars. Periorbital location is the most common cutaneous site of involvement of NXG, seen in 80% of cases, but the trunk and extremities also may be involved.^1,3 Approximately half of those with periocular involvement experience ocular symptoms including prop- tosis, blepharoptosis, and restricted eye movements.⁴ The onset of NXG most commonly is seen in middle age.

Characteristic systemic associations have been reported in the setting of NXG. More than 20% of patients may exhibit hepatomegaly. Hematologic abnormalities, hyperlipidemia, and cryoglobulinemia also may be seen.¹ In addition, a monoclonal gammopathy of uncertain significance is found in more than 80% of NXG cases. The IgG κ light chain is most commonly identified.² A foreign body reaction is incited by the immunoglobulin-lipid complex, which is thought to contribute to the formation of cutaneous lesions. There may be associated plasma cell dyscrasia such as multiple myeloma or B-cell lymphoma in approximately 13% of cases.² Evaluation for underlying plasma cell dyscrasia or lymphoproliferative disorder should be performed regularly with serum protein electrophoresis or immunofixation electrophoresis, and in some cases full-body imaging with computed tomography or magnetic resonance imaging may be warranted.¹

Treatment of NXG often is unsuccessful. Surgical excision, systemic immunosuppressive agents, electron beam radiation, and destructive therapies such as cryotherapy may be trialed, often with little success.¹ Cutaneous regression has been reported with combination treatment of high-dose dexamethasone and high-dose lenalidomide.⁵

The Diagnosis: Necrobiotic Xanthogranuloma

A 4-mm punch biopsy was performed for routine stain with hematoxylin and eosin. The differential diagnosis included sarcoidosis, necrobiosis lipoidica, xanthoma disseminatum, and multicentric reticulohistiocytosis. Histopathologic examination demonstrated a dermal infiltrate of foamy histiocytes and neutrophils (Figure). There were surrounding areas of degenerated collagen containing numerous cholesterol clefts. After clinical pathologic correlation, a diagnosis of necrobiotic xanthogranuloma (NXG) was elucidated.

The patient was referred to general surgery for elective excision of 1 or more of the lesions. Excision of an abdominal lesion was performed without complication. After several months, a new lesion reformed within the excisional scar that also was consistent with NXG. At further dermatologic visits, a trial of intralesional corticosteroids was attempted to the largest lesions with modest improvement. In addition, follow-up with hematology and oncology was recommended for routine surveillance of the known blood dyscrasia.

Necrobiotic xanthogranuloma is a multisystem non-Langerhans cell histiocytic disease. Clinically, NXG is characterized by infiltrative plaques and ulcerative nodules. Lesions may appear red, brown, or yellow with associated atrophy and telangiectasia.¹ Koch et al² described a predilection for granuloma formation within preexisting scars. Periorbital location is the most common cutaneous site of involvement of NXG, seen in 80% of cases, but the trunk and extremities also may be involved.^1,3 Approximately half of those with periocular involvement experience ocular symptoms including prop- tosis, blepharoptosis, and restricted eye movements.⁴ The onset of NXG most commonly is seen in middle age.

Characteristic systemic associations have been reported in the setting of NXG. More than 20% of patients may exhibit hepatomegaly. Hematologic abnormalities, hyperlipidemia, and cryoglobulinemia also may be seen.¹ In addition, a monoclonal gammopathy of uncertain significance is found in more than 80% of NXG cases. The IgG κ light chain is most commonly identified.² A foreign body reaction is incited by the immunoglobulin-lipid complex, which is thought to contribute to the formation of cutaneous lesions. There may be associated plasma cell dyscrasia such as multiple myeloma or B-cell lymphoma in approximately 13% of cases.² Evaluation for underlying plasma cell dyscrasia or lymphoproliferative disorder should be performed regularly with serum protein electrophoresis or immunofixation electrophoresis, and in some cases full-body imaging with computed tomography or magnetic resonance imaging may be warranted.¹

Treatment of NXG often is unsuccessful. Surgical excision, systemic immunosuppressive agents, electron beam radiation, and destructive therapies such as cryotherapy may be trialed, often with little success.¹ Cutaneous regression has been reported with combination treatment of high-dose dexamethasone and high-dose lenalidomide.⁵

The Diagnosis: Necrobiotic Xanthogranuloma

A 4-mm punch biopsy was performed for routine stain with hematoxylin and eosin. The differential diagnosis included sarcoidosis, necrobiosis lipoidica, xanthoma disseminatum, and multicentric reticulohistiocytosis. Histopathologic examination demonstrated a dermal infiltrate of foamy histiocytes and neutrophils (Figure). There were surrounding areas of degenerated collagen containing numerous cholesterol clefts. After clinical pathologic correlation, a diagnosis of necrobiotic xanthogranuloma (NXG) was elucidated.

The patient was referred to general surgery for elective excision of 1 or more of the lesions. Excision of an abdominal lesion was performed without complication. After several months, a new lesion reformed within the excisional scar that also was consistent with NXG. At further dermatologic visits, a trial of intralesional corticosteroids was attempted to the largest lesions with modest improvement. In addition, follow-up with hematology and oncology was recommended for routine surveillance of the known blood dyscrasia.

Necrobiotic xanthogranuloma is a multisystem non-Langerhans cell histiocytic disease. Clinically, NXG is characterized by infiltrative plaques and ulcerative nodules. Lesions may appear red, brown, or yellow with associated atrophy and telangiectasia.¹ Koch et al² described a predilection for granuloma formation within preexisting scars. Periorbital location is the most common cutaneous site of involvement of NXG, seen in 80% of cases, but the trunk and extremities also may be involved.^1,3 Approximately half of those with periocular involvement experience ocular symptoms including prop- tosis, blepharoptosis, and restricted eye movements.⁴ The onset of NXG most commonly is seen in middle age.

Characteristic systemic associations have been reported in the setting of NXG. More than 20% of patients may exhibit hepatomegaly. Hematologic abnormalities, hyperlipidemia, and cryoglobulinemia also may be seen.¹ In addition, a monoclonal gammopathy of uncertain significance is found in more than 80% of NXG cases. The IgG κ light chain is most commonly identified.² A foreign body reaction is incited by the immunoglobulin-lipid complex, which is thought to contribute to the formation of cutaneous lesions. There may be associated plasma cell dyscrasia such as multiple myeloma or B-cell lymphoma in approximately 13% of cases.² Evaluation for underlying plasma cell dyscrasia or lymphoproliferative disorder should be performed regularly with serum protein electrophoresis or immunofixation electrophoresis, and in some cases full-body imaging with computed tomography or magnetic resonance imaging may be warranted.¹

Treatment of NXG often is unsuccessful. Surgical excision, systemic immunosuppressive agents, electron beam radiation, and destructive therapies such as cryotherapy may be trialed, often with little success.¹ Cutaneous regression has been reported with combination treatment of high-dose dexamethasone and high-dose lenalidomide.⁵

Rituximab was associated with a lower drug discontinuation rate versus all other commonly prescribed disease-modifying treatments (DMTs) used as initial therapy for relapsing-remitting multiple sclerosis (RRMS) in a retrospective study of patient data from a Swedish multiple sclerosis registry.

In addition, relapse rates were lower with rituximab (Rituxan) than they were with injectable DMTs and dimethyl fumarate (Tecfidera), according to results of the study, which appeared online Jan. 8 in JAMA Neurology.

designer491/Thinkstock

[email protected]

SOURCE: Granqvist M et al. JAMA Neurol. 2018 Jan 8. doi: 10.1001/jamaneurol.2017.4011

Rituximab was associated with a lower drug discontinuation rate versus all other commonly prescribed disease-modifying treatments (DMTs) used as initial therapy for relapsing-remitting multiple sclerosis (RRMS) in a retrospective study of patient data from a Swedish multiple sclerosis registry.

In addition, relapse rates were lower with rituximab (Rituxan) than they were with injectable DMTs and dimethyl fumarate (Tecfidera), according to results of the study, which appeared online Jan. 8 in JAMA Neurology.

designer491/Thinkstock

[email protected]

SOURCE: Granqvist M et al. JAMA Neurol. 2018 Jan 8. doi: 10.1001/jamaneurol.2017.4011

Rituximab was associated with a lower drug discontinuation rate versus all other commonly prescribed disease-modifying treatments (DMTs) used as initial therapy for relapsing-remitting multiple sclerosis (RRMS) in a retrospective study of patient data from a Swedish multiple sclerosis registry.

In addition, relapse rates were lower with rituximab (Rituxan) than they were with injectable DMTs and dimethyl fumarate (Tecfidera), according to results of the study, which appeared online Jan. 8 in JAMA Neurology.

designer491/Thinkstock

[email protected]

SOURCE: Granqvist M et al. JAMA Neurol. 2018 Jan 8. doi: 10.1001/jamaneurol.2017.4011

“CLINICAL CORRELATION OF SUCCESS AND ACUTE THROMBOTIC COMPLICATIONS OF LOWER EXTREMITY ENDOVENOUS THERMAL ABLATION.” Journal of Vascular Surgery Venous and Lymphatic Disorders, January 2018

A large single center experience with endovenous thermal ablation reveals risk factors for thrombotic complications.

Minimally invasive techniques for treating reflux disease in the saphenous system have greatly improved the quality of life and comfort of those suffering with chronic venous disease and more advanced venous insufficiency.  Painful procedures of the past, sometimes including hospital stays, have largely been replaced by safe and efficacious office procedures (lasting often less than an hour) with minimal subsequent activity restrictions.

Despite these obvious advantages, these therapies do have a very low but definite risk of thrombotic complications, including endovenous heat-induced thrombosis (EHIT) superficial venous thrombosis (SVT) and deep vein thrombosis (DVT).  EHIT includes development of a blood clot at the junction of one of the treated saphenous veins and the femoral or the popliteal vein.

While major DVT and pulmonary embolism are extremely rare, the diagnosis of EHIT may require a period of anticoagulation as well as follow-up visits and studies.  Further, acute SVT can be painful for several weeks following the procedure.  As such, further understanding the risk factors for these complications will allow therapists to better inform patients as to their specific risks for developing them.

As reported in the January 2018 edition of the Journal of Vascular Surgery: Venous and Lymphatic Disorders, researchers from Total Vascular Care and NYU Lutheran Medical Center led by Afsha Aurshina, MBBS, evaluated their large single center experience treating multiple vein types using both radiofrequency (RFA) and endovenous laser (EVLA) ablation techniques.  They retrospectively studied the outcomes of 1811 procedures performed on 808 patients from 2012-2014.  The aim of the study was to define better the success and thrombotic complications of these procedures with respect to technique and vein type.

Overall success (defined as absence of reflux in the targeted vein by post-operative duplex) rates included:

• RFA                                              98.4% (excluding perforating vein)
• EVLA                                            98.1%
• Great saphenous (GSV)                 98.5%
• Lesser saphenous (LSV)                98.2%
• Accessory saphenous (ASV)          97.2%
• Perforator (PV)                             82.4%

With regards to thrombotic complications, the authors reported EHIT rates of:

• Class 1-4                                    5.9%
• Class 2-4                                    1.16%

Acute superficial thrombosis rates included:

• Overall                                                4.6%
• RFA                                                     7.7%
• EVLA                                                  11.4% (no difference in multi-factor analysis)
• GSV                                                   11.8%
• LSV                                                     5.5%
• ASV                                                    6.5%
• PV                                                      2.4%

“Our study demonstrates that there is no significant difference in the success rate of RFA and EVLA in the treatment of venous reflux for GSV, SSV, and ASV,” notes first author Aurshina.  “We found an acceptably low incidence of clinically significant thrombotic complication rates for EHIT and acute superficial thrombosis, with only a 1.16% risk of Class 2-4 EHIT, that may require short term anticoagulation.  We noted risk factors for these complications, after multi-factor analysis, include higher vein diameter and type of vein, with the latter being the most important.”

Large experiences such as these are important to understand the true incidence of these complications and how practitioners might tailor their consent process with their patients.

To download the complete article (link available free from 12/14/2017 through 2/28/2018),

 click:  http://vsweb.org/JVSVL-EVTA
 

For information your patients may be interested in, click:

Regarding Varicose Veins:

https://vascular.org/patient-resources/vascular-conditions/varicose-veins

Regarding Deep Venous Thrombosis:

https://vascular.org/patient-resources/vascular-conditions/deep-vein-thrombosis

“CLINICAL CORRELATION OF SUCCESS AND ACUTE THROMBOTIC COMPLICATIONS OF LOWER EXTREMITY ENDOVENOUS THERMAL ABLATION.” Journal of Vascular Surgery Venous and Lymphatic Disorders, January 2018

A large single center experience with endovenous thermal ablation reveals risk factors for thrombotic complications.

Minimally invasive techniques for treating reflux disease in the saphenous system have greatly improved the quality of life and comfort of those suffering with chronic venous disease and more advanced venous insufficiency.  Painful procedures of the past, sometimes including hospital stays, have largely been replaced by safe and efficacious office procedures (lasting often less than an hour) with minimal subsequent activity restrictions.

Despite these obvious advantages, these therapies do have a very low but definite risk of thrombotic complications, including endovenous heat-induced thrombosis (EHIT) superficial venous thrombosis (SVT) and deep vein thrombosis (DVT).  EHIT includes development of a blood clot at the junction of one of the treated saphenous veins and the femoral or the popliteal vein.

While major DVT and pulmonary embolism are extremely rare, the diagnosis of EHIT may require a period of anticoagulation as well as follow-up visits and studies.  Further, acute SVT can be painful for several weeks following the procedure.  As such, further understanding the risk factors for these complications will allow therapists to better inform patients as to their specific risks for developing them.

As reported in the January 2018 edition of the Journal of Vascular Surgery: Venous and Lymphatic Disorders, researchers from Total Vascular Care and NYU Lutheran Medical Center led by Afsha Aurshina, MBBS, evaluated their large single center experience treating multiple vein types using both radiofrequency (RFA) and endovenous laser (EVLA) ablation techniques.  They retrospectively studied the outcomes of 1811 procedures performed on 808 patients from 2012-2014.  The aim of the study was to define better the success and thrombotic complications of these procedures with respect to technique and vein type.

Overall success (defined as absence of reflux in the targeted vein by post-operative duplex) rates included:

• RFA                                              98.4% (excluding perforating vein)
• EVLA                                            98.1%
• Great saphenous (GSV)                 98.5%
• Lesser saphenous (LSV)                98.2%
• Accessory saphenous (ASV)          97.2%
• Perforator (PV)                             82.4%

With regards to thrombotic complications, the authors reported EHIT rates of:

• Class 1-4                                    5.9%
• Class 2-4                                    1.16%

Acute superficial thrombosis rates included:

• Overall                                                4.6%
• RFA                                                     7.7%
• EVLA                                                  11.4% (no difference in multi-factor analysis)
• GSV                                                   11.8%
• LSV                                                     5.5%
• ASV                                                    6.5%
• PV                                                      2.4%

“Our study demonstrates that there is no significant difference in the success rate of RFA and EVLA in the treatment of venous reflux for GSV, SSV, and ASV,” notes first author Aurshina.  “We found an acceptably low incidence of clinically significant thrombotic complication rates for EHIT and acute superficial thrombosis, with only a 1.16% risk of Class 2-4 EHIT, that may require short term anticoagulation.  We noted risk factors for these complications, after multi-factor analysis, include higher vein diameter and type of vein, with the latter being the most important.”

Large experiences such as these are important to understand the true incidence of these complications and how practitioners might tailor their consent process with their patients.

To download the complete article (link available free from 12/14/2017 through 2/28/2018),

 click:  http://vsweb.org/JVSVL-EVTA
 

For information your patients may be interested in, click:

Regarding Varicose Veins:

https://vascular.org/patient-resources/vascular-conditions/varicose-veins

Regarding Deep Venous Thrombosis:

https://vascular.org/patient-resources/vascular-conditions/deep-vein-thrombosis

“CLINICAL CORRELATION OF SUCCESS AND ACUTE THROMBOTIC COMPLICATIONS OF LOWER EXTREMITY ENDOVENOUS THERMAL ABLATION.” Journal of Vascular Surgery Venous and Lymphatic Disorders, January 2018

A large single center experience with endovenous thermal ablation reveals risk factors for thrombotic complications.

Minimally invasive techniques for treating reflux disease in the saphenous system have greatly improved the quality of life and comfort of those suffering with chronic venous disease and more advanced venous insufficiency.  Painful procedures of the past, sometimes including hospital stays, have largely been replaced by safe and efficacious office procedures (lasting often less than an hour) with minimal subsequent activity restrictions.

Despite these obvious advantages, these therapies do have a very low but definite risk of thrombotic complications, including endovenous heat-induced thrombosis (EHIT) superficial venous thrombosis (SVT) and deep vein thrombosis (DVT).  EHIT includes development of a blood clot at the junction of one of the treated saphenous veins and the femoral or the popliteal vein.

While major DVT and pulmonary embolism are extremely rare, the diagnosis of EHIT may require a period of anticoagulation as well as follow-up visits and studies.  Further, acute SVT can be painful for several weeks following the procedure.  As such, further understanding the risk factors for these complications will allow therapists to better inform patients as to their specific risks for developing them.

As reported in the January 2018 edition of the Journal of Vascular Surgery: Venous and Lymphatic Disorders, researchers from Total Vascular Care and NYU Lutheran Medical Center led by Afsha Aurshina, MBBS, evaluated their large single center experience treating multiple vein types using both radiofrequency (RFA) and endovenous laser (EVLA) ablation techniques.  They retrospectively studied the outcomes of 1811 procedures performed on 808 patients from 2012-2014.  The aim of the study was to define better the success and thrombotic complications of these procedures with respect to technique and vein type.

Overall success (defined as absence of reflux in the targeted vein by post-operative duplex) rates included:

• RFA                                              98.4% (excluding perforating vein)
• EVLA                                            98.1%
• Great saphenous (GSV)                 98.5%
• Lesser saphenous (LSV)                98.2%
• Accessory saphenous (ASV)          97.2%
• Perforator (PV)                             82.4%

With regards to thrombotic complications, the authors reported EHIT rates of:

• Class 1-4                                    5.9%
• Class 2-4                                    1.16%

Acute superficial thrombosis rates included:

• Overall                                                4.6%
• RFA                                                     7.7%
• EVLA                                                  11.4% (no difference in multi-factor analysis)
• GSV                                                   11.8%
• LSV                                                     5.5%
• ASV                                                    6.5%
• PV                                                      2.4%

“Our study demonstrates that there is no significant difference in the success rate of RFA and EVLA in the treatment of venous reflux for GSV, SSV, and ASV,” notes first author Aurshina.  “We found an acceptably low incidence of clinically significant thrombotic complication rates for EHIT and acute superficial thrombosis, with only a 1.16% risk of Class 2-4 EHIT, that may require short term anticoagulation.  We noted risk factors for these complications, after multi-factor analysis, include higher vein diameter and type of vein, with the latter being the most important.”

Large experiences such as these are important to understand the true incidence of these complications and how practitioners might tailor their consent process with their patients.

To download the complete article (link available free from 12/14/2017 through 2/28/2018),

 click:  http://vsweb.org/JVSVL-EVTA
 

For information your patients may be interested in, click:

Regarding Varicose Veins:

https://vascular.org/patient-resources/vascular-conditions/varicose-veins

Regarding Deep Venous Thrombosis:

https://vascular.org/patient-resources/vascular-conditions/deep-vein-thrombosis

Registration is now open for the Vascular Research Initiatives Conference, to be held Thursday, May 9, in San Francisco. Abstracts for VRIC are due Wednesday, Jan. 10. Learn more about VRIC, and submit your abstracts here. 

Registration is now open for the Vascular Research Initiatives Conference, to be held Thursday, May 9, in San Francisco. Abstracts for VRIC are due Wednesday, Jan. 10. Learn more about VRIC, and submit your abstracts here. 

Registration is now open for the Vascular Research Initiatives Conference, to be held Thursday, May 9, in San Francisco. Abstracts for VRIC are due Wednesday, Jan. 10. Learn more about VRIC, and submit your abstracts here. 

Have you put off paying your 2018 SVS membership dues? Don’t wait too much longer! Access to the Journal of Vascular Surgery suite of publications expires on Jan. 15 for those who have not yet paid their 2018 dues. Renew today.

Have you put off paying your 2018 SVS membership dues? Don’t wait too much longer! Access to the Journal of Vascular Surgery suite of publications expires on Jan. 15 for those who have not yet paid their 2018 dues. Renew today.

Have you put off paying your 2018 SVS membership dues? Don’t wait too much longer! Access to the Journal of Vascular Surgery suite of publications expires on Jan. 15 for those who have not yet paid their 2018 dues. Renew today.

Abstracts are due Wednesday, Jan. 17, for the 2018 Vascular Annual Meeting, set for June 20-23 in Boston. Guidelines, submission policies and general information on VAM are available online. VAM plenaries are June 21-23 and exhibits are June 21-22. Registration and housing will open in early March.

Abstracts are due Wednesday, Jan. 17, for the 2018 Vascular Annual Meeting, set for June 20-23 in Boston. Guidelines, submission policies and general information on VAM are available online. VAM plenaries are June 21-23 and exhibits are June 21-22. Registration and housing will open in early March.

Abstracts are due Wednesday, Jan. 17, for the 2018 Vascular Annual Meeting, set for June 20-23 in Boston. Guidelines, submission policies and general information on VAM are available online. VAM plenaries are June 21-23 and exhibits are June 21-22. Registration and housing will open in early March.

Regenerative medicine encompasses innovative therapies that allow the body to repair or regenerate aging cells, tissues, and organs. The skin is a particularly attractive organ for the application of novel regenerative therapies due to its easy accessibility. Among these therapies, stem cells and platelet-rich plasma (PRP) have garnered interest based on their therapeutic potential in scar reduction, antiaging effects, and treatment of alopecia.

Stem cells possess the cardinal features of self-renewal and plasticity. Self-renewal refers to symmetric cell division generating daughter cells identical to the parent cell.¹ Plasticity is the ability to generate cell types other than the germ line or tissue lineage from which stem cells derive.² Stem cells can be categorized according to their differentiation potential. Totipotent stem cells may develop into any primary germ cell layer (ectoderm, mesoderm, endoderm) of the embryo, as well as extraembryonic tissue such as the trophoblast, which gives rise to the placenta. Pluripotent stem cells such as embryonic stem cells have the capacity to differentiate into any derivative of the 3 germ cell layers but have lost their ability to differentiate into the trophoblast.³ Adults lack totipotent or pluripotent cells; they have multipotent or unipotent cells. Multipotent stem cells are able to differentiate into multiple cell types from similar lineages; mesenchymal stem cells (MSCs), for example, can differentiate into adipogenic, osteogenic, chondrogenic, and myogenic cells.⁴ Unipotent stem cells have the lowest differentiation potential and can only self-regenerate. Herein, we review stem cell sources and their therapeutic potential in aesthetic dermatology.

Multipotent Stem Cells

Multipotent stem cells derived from the bone marrow, umbilical cord, adipose tissue, dermis, or hair follicle bulge have various clinical applications in dermatology. Stem cells from these sources are primarily utilized in an autologous manner in which they are processed outside the body and reintroduced into the donor. Autologous multipotent hematopoietic bone marrow cells were first successfully used for the treatment of chronic wounds and show promise for the treatment of atrophic scars.^5,6 However, due to the invasive nature of extracting bone marrow stem cells and their declining number with age, other sources of multipotent stem cells have fallen into favor.

Umbilical cord blood is a source of multipotent hematopoietic stem cells for which surgical intervention is not necessary because they are retrieved after umbilical cord clamping.⁷ Advantages of sourcing stem cells from umbilical cord blood includes high regenerative power compared to a newborn’s skin and low immunogenicity given that the newborn is immunologically immature.⁸

Another popular source for autologous stem cells is adipose tissue due to its ease of accessibility and relative abundance. Given that adipose tissue–derived stem cells (ASCs) are capable of differentiating into adipocytes that help maintain volume over time, they are being used for midface contouring, lip augmentation, facial rejuvenation, facial scarring, lipodystrophy, penile girth enhancement, and vaginal augmentation. Adipose tissue–derived stem cells also are capable of differentiating into other types of tissue, including cartilage and bone. Thus, they have been successfully harnessed in the treatment of patients affected by systemic sclerosis and Parry-Romberg syndrome as well in the functional and aesthetic reconstruction of various military combat–related deformities.^9,10

Adipose tissue–derived stem cells are commonly harvested from lipoaspirate of the abdomen and are combined with supportive mechanical scaffolds such as hydrogels. Lipoaspirate itself can serve as a scaffold for ASCs. Accordingly, ASCs also are being utilized as a scaffold for autologous fat transfer procedures in an effort to increase the viability of transplanted donor tissue, a process known as cell-assisted lipotransfer (CAL). In CAL, a fraction of the aspirated fat is processed for isolation of ASCs, which are then recombined with the remainder of the aspirated fat prior to grafting.¹¹ However, there is conflicting evidence as to whether CAL leads to improved graft success relative to conventional autologous fat transfer.^12,13

The skin also serves as an easily accessible and abundant autologous source of stem cells. A subtype of dermal fibroblasts has been proven to have multipotent potential.^14,15 These dermal fibroblasts are harvested from one area of the skin using punch biopsy and are processed and reinjected into another desired area of the skin.¹⁶ Autologous human fibroblasts have proven to be effective for the treatment of wrinkles, rhytides, and acne scars.¹⁷ In June 2011, the US Food and Drug Administration approved azficel-T, an autologous cellular product created by harvesting fibroblasts from a patient’s own postauricular skin, culture-expanding them in vitro for 3 months, and reinjecting the cells into the desired area of dermis in a series of treatments. This product was the first personalized cell therapy approved by the US Food and Drug Administration for aesthetic uses, specifically for the improvement of nasolabial fold wrinkles.¹⁸

In adults, hair follicles contain an area known as the bulge, which is a site rich in epithelial and melanocytic stem cells. Bulge stem cells have the ability to reproduce the interfollicular epidermis, hair follicle structures, and sebaceous glands, and they have been used to construct entirely new hair follicles in an artificial in vivo system.¹⁹ Sugiyama-Nakagiri et al²⁰ demonstrated that an entire hair follicle epithelium and interfollicular epidermis can be regenerated using cultured bulge stem cells. The cultured bulge stem cells were mixed with dermal papilla cells from neonatal rat vibrissae and engrafted into a silicone chamber implanted on the backs of severe combined immune deficient (SCID) mice. The grafts exhibited tufts of hair as well as a complete interfollicular epidermis at 4 weeks after transplantation.²⁰ Thus, these bulge stem cells have the potential to treat male androgenic alopecia and female pattern hair loss. Bulge stem cells also have been shown to accelerate wound healing.²¹ Additionally, autologous melanocytic stem cells located at the hair follicle bulge are effective for treating vitiligo and are being investigated for the treatment of hair graying.²²

Induced Pluripotent Stem Cells

Given the ethical concerns that surround the procurement and use of embryonic stem cells, efforts have been made to retrieve pluripotent stem cells from adults. A major breakthrough occurred in 2006 when researchers altered the genes of specialized adult mouse cells to cause dedifferentiation and the return to an embryoniclike stem cell state.²³ Mouse somatic cells were reprogrammed through the activation of a combination of transcription factors. The resulting cells were termed induced pluripotent stem cells (iPSCs) and have since been recreated in human cell lines. The discovery of iPSCs precipitated a translational science revolution. Physician-scientists sought ways to apply the reprogrammed cells to the pathophysiology of obscure diseases, examination of drug targets, and regeneration of human tissue.²⁴ Tissue regeneration via induced naïve somatic cells has shown promise as a future method to treat neurologic, cardiovascular, and ophthalmologic diseases.²⁵

As the technology of cultivating and identifying optimal sources of iPSCs continues to advance, stem cell–based treatments have evolved as leading prospects in the field of biogerontology.^26-29 Although much of the research in antiaging medicine has utilized iPSCs to reprogram cell senescence, the altering of iPSCs at a cellular level also allows for the stimulation of collagen synthesis. This potential for collagen generation may have direct applicability in dermatologic practice, particularly for aesthetic treatments.

Much of the research into iPSC-derived collagen has focused on genodermatoses. Itoh et al³⁰ examined the creation of collagen through iPSCs to identify possible treatments for recessive dystrophic epidermolysis bullosa (DEB). Recessive DEB is characterized by mutations in the COL7A1 gene, which encodes type VII collagen, a basement membrane protein and component of the anchoring fibrils essential for skin integrity.³¹ Itoh et al³⁰ began with source cells obtained from a skin biopsy. The cells were dedifferentiated to iPSCs and then induced into dermal fibroblasts according to the methods established in prior studies of embryonic stem cells, namely with the use of ascorbic acid and transforming growth factor b. The newly formed fibroblasts were determined to be functional based on their ability to synthesize mature type VII collagen.³⁰ Once the viability of the iPSC-derived fibroblasts was confirmed in vitro, the cells were further tested through combination with human keratinocytes on SCID mice. The human keratinocytes grew together with the iPSC-derived fibroblasts, producing type VII collagen in the basement membrane zone and creating an epidermis with the normal markers.³⁰ Similarly, Robbins et al³² utilized SCID mice to successfully demonstrate that the transfection of keratinocytes from patients with junctional epidermolysis bullosa into SCID mice produced phenotypically normal skin.

Sebastiano et al³³ combined the concepts of iPSCs and genome editing in another study of recessive DEB. The investigators first cultured iPSCs from biopsies of affected patients. After deriving iPSCs and correcting their mutation via adenovirus-associated viral gene editing, the COL7A1 mutation-free cells were differentiated into keratinocytes. These iPSC-derived keratinocytes were subsequently grafted onto mice, which led to the production of wild-type collagen VII and a stratified epidermis. Despite this successful outcome, the grafts of iPSC-derived epidermis did not survive longer than 1 month.³³

One of the many obstacles facing the practical use of stem cells is their successful incorporation into human tissue. A possible solution was uncovered by Zhang et al³⁴ who examined iPSC-derived MSCs. Mesenchymal stem cells communicate via paracrine mechanisms, whereby exosomes containing RNA and proteins are released to potentiate a regenerative effect.³⁵ Zhang et al³⁴ found that injecting exosomes from human iPSC-derived MSCs into the wound sites of rats stimulated the production of type I collagen, type III collagen, and elastin. The wound sites demonstrated accelerated closure, narrower scar widths, and increased collagen maturity.

Understanding the role that local environment plays in stem cell differentiation, Xu et al³⁶ aimed to create an extracellular scaffold to induce fibroblast behavior from iPSCs. The authors engineered a framework similar to the normal extracellular membrane using proteoglycans, glycosaminoglycans, fibrinogen, and connective tissue growth factor. The iPSCs were then applied to the scaffolding, which led to successful fibroblast differentiation and type I collagen synthesis.³⁶ This use of local biosignaling cues holds important ramifications for controlling the fate of stem cells that have been introduced into a new environment.

Although the application of iPSCs in clinical dermatology has yet to be achieved, progress in the field is moving at a rapid pace. Several logistical elements require further mastery before therapeutics can be delivered. These areas include the optimal environment for iPSC differentiation, methods for maximization of graft survival, and different modes of transplanting iPSC-derived cells into patients. In cosmetic practice, success will depend on intradermal injections of collagen-producing iPSC-derived cells that possess long-term proliferative potential. Current research in mice models has demonstrated viability up to 16 weeks after intradermal injection of such cells.³⁷

Plant Stem Cells

In discussing the dermatologic applications of stem cell technology, clinicians should be aware of the plant stem cell products that have become a popular cosmeceutical trend. Companies advertise plant cells as a natural source of regenerative cells that can induce rejuvenation in human skin; however, there are no significant data to indicate that plant stem cells encourage or activate cellular growth in humans. Indeed, for stem cells to differentiate and produce viable components, the cells must first be incorporated as living components in the host tissue. Because plant stem cells do not survive in human tissue and plant cell cytokines fail to interact with the receptors on human cells, their current value in cosmeceuticals may be overstated.

Platelet-Rich Plasma

Platelet-rich plasma also is commonly associated with stem cell therapy, as PRP is known to potentiate stem cell proliferation, migration, and differentiation. However, PRP does not contain stem cells and is instead autologous plasma concentrated with platelets. In fact, platelets cannot even be classified as cells given that they lack a nucleus; platelets are considered cell fragments. The regenerative potential of PRP can be attributed to the growth factors released from platelets, which play an important role in tissue regeneration and repair. Platelet-rich plasma currently is being used in dermatology for skin rejuvenation (reduction of wrinkles and furrows) and treatment of acne scars.³⁸ There also is evidence supporting the effectiveness of PRP for alopecia and wound therapy, as growth factors play a vital role in hair growth and wound healing.³⁸ Apart from the use of PRP on its own, it can be used as a supplement to enhance the effects of antiaging procedures such as microneedling.³⁹

Future Directions

Multipotent stem cells and iPSCs discussed herein provide much promise in the field of regenerative dermatology. They are increasingly accessible and circumvent the use of ethically questionable embryonic stem cells. Although there is a general consensus on the great potential of stem cells for treating aesthetic skin conditions, high-quality randomized controlled trials remain scarce within the literature. Recognizing and optimizing these opportunities remains the next step in the future delivery of evidence-based care in regenerative dermatology.

Regenerative medicine encompasses innovative therapies that allow the body to repair or regenerate aging cells, tissues, and organs. The skin is a particularly attractive organ for the application of novel regenerative therapies due to its easy accessibility. Among these therapies, stem cells and platelet-rich plasma (PRP) have garnered interest based on their therapeutic potential in scar reduction, antiaging effects, and treatment of alopecia.

Stem cells possess the cardinal features of self-renewal and plasticity. Self-renewal refers to symmetric cell division generating daughter cells identical to the parent cell.¹ Plasticity is the ability to generate cell types other than the germ line or tissue lineage from which stem cells derive.² Stem cells can be categorized according to their differentiation potential. Totipotent stem cells may develop into any primary germ cell layer (ectoderm, mesoderm, endoderm) of the embryo, as well as extraembryonic tissue such as the trophoblast, which gives rise to the placenta. Pluripotent stem cells such as embryonic stem cells have the capacity to differentiate into any derivative of the 3 germ cell layers but have lost their ability to differentiate into the trophoblast.³ Adults lack totipotent or pluripotent cells; they have multipotent or unipotent cells. Multipotent stem cells are able to differentiate into multiple cell types from similar lineages; mesenchymal stem cells (MSCs), for example, can differentiate into adipogenic, osteogenic, chondrogenic, and myogenic cells.⁴ Unipotent stem cells have the lowest differentiation potential and can only self-regenerate. Herein, we review stem cell sources and their therapeutic potential in aesthetic dermatology.

Multipotent Stem Cells

Multipotent stem cells derived from the bone marrow, umbilical cord, adipose tissue, dermis, or hair follicle bulge have various clinical applications in dermatology. Stem cells from these sources are primarily utilized in an autologous manner in which they are processed outside the body and reintroduced into the donor. Autologous multipotent hematopoietic bone marrow cells were first successfully used for the treatment of chronic wounds and show promise for the treatment of atrophic scars.^5,6 However, due to the invasive nature of extracting bone marrow stem cells and their declining number with age, other sources of multipotent stem cells have fallen into favor.

Umbilical cord blood is a source of multipotent hematopoietic stem cells for which surgical intervention is not necessary because they are retrieved after umbilical cord clamping.⁷ Advantages of sourcing stem cells from umbilical cord blood includes high regenerative power compared to a newborn’s skin and low immunogenicity given that the newborn is immunologically immature.⁸

Another popular source for autologous stem cells is adipose tissue due to its ease of accessibility and relative abundance. Given that adipose tissue–derived stem cells (ASCs) are capable of differentiating into adipocytes that help maintain volume over time, they are being used for midface contouring, lip augmentation, facial rejuvenation, facial scarring, lipodystrophy, penile girth enhancement, and vaginal augmentation. Adipose tissue–derived stem cells also are capable of differentiating into other types of tissue, including cartilage and bone. Thus, they have been successfully harnessed in the treatment of patients affected by systemic sclerosis and Parry-Romberg syndrome as well in the functional and aesthetic reconstruction of various military combat–related deformities.^9,10

Adipose tissue–derived stem cells are commonly harvested from lipoaspirate of the abdomen and are combined with supportive mechanical scaffolds such as hydrogels. Lipoaspirate itself can serve as a scaffold for ASCs. Accordingly, ASCs also are being utilized as a scaffold for autologous fat transfer procedures in an effort to increase the viability of transplanted donor tissue, a process known as cell-assisted lipotransfer (CAL). In CAL, a fraction of the aspirated fat is processed for isolation of ASCs, which are then recombined with the remainder of the aspirated fat prior to grafting.¹¹ However, there is conflicting evidence as to whether CAL leads to improved graft success relative to conventional autologous fat transfer.^12,13

The skin also serves as an easily accessible and abundant autologous source of stem cells. A subtype of dermal fibroblasts has been proven to have multipotent potential.^14,15 These dermal fibroblasts are harvested from one area of the skin using punch biopsy and are processed and reinjected into another desired area of the skin.¹⁶ Autologous human fibroblasts have proven to be effective for the treatment of wrinkles, rhytides, and acne scars.¹⁷ In June 2011, the US Food and Drug Administration approved azficel-T, an autologous cellular product created by harvesting fibroblasts from a patient’s own postauricular skin, culture-expanding them in vitro for 3 months, and reinjecting the cells into the desired area of dermis in a series of treatments. This product was the first personalized cell therapy approved by the US Food and Drug Administration for aesthetic uses, specifically for the improvement of nasolabial fold wrinkles.¹⁸

In adults, hair follicles contain an area known as the bulge, which is a site rich in epithelial and melanocytic stem cells. Bulge stem cells have the ability to reproduce the interfollicular epidermis, hair follicle structures, and sebaceous glands, and they have been used to construct entirely new hair follicles in an artificial in vivo system.¹⁹ Sugiyama-Nakagiri et al²⁰ demonstrated that an entire hair follicle epithelium and interfollicular epidermis can be regenerated using cultured bulge stem cells. The cultured bulge stem cells were mixed with dermal papilla cells from neonatal rat vibrissae and engrafted into a silicone chamber implanted on the backs of severe combined immune deficient (SCID) mice. The grafts exhibited tufts of hair as well as a complete interfollicular epidermis at 4 weeks after transplantation.²⁰ Thus, these bulge stem cells have the potential to treat male androgenic alopecia and female pattern hair loss. Bulge stem cells also have been shown to accelerate wound healing.²¹ Additionally, autologous melanocytic stem cells located at the hair follicle bulge are effective for treating vitiligo and are being investigated for the treatment of hair graying.²²

Induced Pluripotent Stem Cells

Given the ethical concerns that surround the procurement and use of embryonic stem cells, efforts have been made to retrieve pluripotent stem cells from adults. A major breakthrough occurred in 2006 when researchers altered the genes of specialized adult mouse cells to cause dedifferentiation and the return to an embryoniclike stem cell state.²³ Mouse somatic cells were reprogrammed through the activation of a combination of transcription factors. The resulting cells were termed induced pluripotent stem cells (iPSCs) and have since been recreated in human cell lines. The discovery of iPSCs precipitated a translational science revolution. Physician-scientists sought ways to apply the reprogrammed cells to the pathophysiology of obscure diseases, examination of drug targets, and regeneration of human tissue.²⁴ Tissue regeneration via induced naïve somatic cells has shown promise as a future method to treat neurologic, cardiovascular, and ophthalmologic diseases.²⁵

As the technology of cultivating and identifying optimal sources of iPSCs continues to advance, stem cell–based treatments have evolved as leading prospects in the field of biogerontology.^26-29 Although much of the research in antiaging medicine has utilized iPSCs to reprogram cell senescence, the altering of iPSCs at a cellular level also allows for the stimulation of collagen synthesis. This potential for collagen generation may have direct applicability in dermatologic practice, particularly for aesthetic treatments.

Much of the research into iPSC-derived collagen has focused on genodermatoses. Itoh et al³⁰ examined the creation of collagen through iPSCs to identify possible treatments for recessive dystrophic epidermolysis bullosa (DEB). Recessive DEB is characterized by mutations in the COL7A1 gene, which encodes type VII collagen, a basement membrane protein and component of the anchoring fibrils essential for skin integrity.³¹ Itoh et al³⁰ began with source cells obtained from a skin biopsy. The cells were dedifferentiated to iPSCs and then induced into dermal fibroblasts according to the methods established in prior studies of embryonic stem cells, namely with the use of ascorbic acid and transforming growth factor b. The newly formed fibroblasts were determined to be functional based on their ability to synthesize mature type VII collagen.³⁰ Once the viability of the iPSC-derived fibroblasts was confirmed in vitro, the cells were further tested through combination with human keratinocytes on SCID mice. The human keratinocytes grew together with the iPSC-derived fibroblasts, producing type VII collagen in the basement membrane zone and creating an epidermis with the normal markers.³⁰ Similarly, Robbins et al³² utilized SCID mice to successfully demonstrate that the transfection of keratinocytes from patients with junctional epidermolysis bullosa into SCID mice produced phenotypically normal skin.

Sebastiano et al³³ combined the concepts of iPSCs and genome editing in another study of recessive DEB. The investigators first cultured iPSCs from biopsies of affected patients. After deriving iPSCs and correcting their mutation via adenovirus-associated viral gene editing, the COL7A1 mutation-free cells were differentiated into keratinocytes. These iPSC-derived keratinocytes were subsequently grafted onto mice, which led to the production of wild-type collagen VII and a stratified epidermis. Despite this successful outcome, the grafts of iPSC-derived epidermis did not survive longer than 1 month.³³

One of the many obstacles facing the practical use of stem cells is their successful incorporation into human tissue. A possible solution was uncovered by Zhang et al³⁴ who examined iPSC-derived MSCs. Mesenchymal stem cells communicate via paracrine mechanisms, whereby exosomes containing RNA and proteins are released to potentiate a regenerative effect.³⁵ Zhang et al³⁴ found that injecting exosomes from human iPSC-derived MSCs into the wound sites of rats stimulated the production of type I collagen, type III collagen, and elastin. The wound sites demonstrated accelerated closure, narrower scar widths, and increased collagen maturity.

Understanding the role that local environment plays in stem cell differentiation, Xu et al³⁶ aimed to create an extracellular scaffold to induce fibroblast behavior from iPSCs. The authors engineered a framework similar to the normal extracellular membrane using proteoglycans, glycosaminoglycans, fibrinogen, and connective tissue growth factor. The iPSCs were then applied to the scaffolding, which led to successful fibroblast differentiation and type I collagen synthesis.³⁶ This use of local biosignaling cues holds important ramifications for controlling the fate of stem cells that have been introduced into a new environment.

Although the application of iPSCs in clinical dermatology has yet to be achieved, progress in the field is moving at a rapid pace. Several logistical elements require further mastery before therapeutics can be delivered. These areas include the optimal environment for iPSC differentiation, methods for maximization of graft survival, and different modes of transplanting iPSC-derived cells into patients. In cosmetic practice, success will depend on intradermal injections of collagen-producing iPSC-derived cells that possess long-term proliferative potential. Current research in mice models has demonstrated viability up to 16 weeks after intradermal injection of such cells.³⁷

Plant Stem Cells

In discussing the dermatologic applications of stem cell technology, clinicians should be aware of the plant stem cell products that have become a popular cosmeceutical trend. Companies advertise plant cells as a natural source of regenerative cells that can induce rejuvenation in human skin; however, there are no significant data to indicate that plant stem cells encourage or activate cellular growth in humans. Indeed, for stem cells to differentiate and produce viable components, the cells must first be incorporated as living components in the host tissue. Because plant stem cells do not survive in human tissue and plant cell cytokines fail to interact with the receptors on human cells, their current value in cosmeceuticals may be overstated.

Platelet-Rich Plasma

Platelet-rich plasma also is commonly associated with stem cell therapy, as PRP is known to potentiate stem cell proliferation, migration, and differentiation. However, PRP does not contain stem cells and is instead autologous plasma concentrated with platelets. In fact, platelets cannot even be classified as cells given that they lack a nucleus; platelets are considered cell fragments. The regenerative potential of PRP can be attributed to the growth factors released from platelets, which play an important role in tissue regeneration and repair. Platelet-rich plasma currently is being used in dermatology for skin rejuvenation (reduction of wrinkles and furrows) and treatment of acne scars.³⁸ There also is evidence supporting the effectiveness of PRP for alopecia and wound therapy, as growth factors play a vital role in hair growth and wound healing.³⁸ Apart from the use of PRP on its own, it can be used as a supplement to enhance the effects of antiaging procedures such as microneedling.³⁹

Future Directions

Multipotent stem cells and iPSCs discussed herein provide much promise in the field of regenerative dermatology. They are increasingly accessible and circumvent the use of ethically questionable embryonic stem cells. Although there is a general consensus on the great potential of stem cells for treating aesthetic skin conditions, high-quality randomized controlled trials remain scarce within the literature. Recognizing and optimizing these opportunities remains the next step in the future delivery of evidence-based care in regenerative dermatology.

Regenerative medicine encompasses innovative therapies that allow the body to repair or regenerate aging cells, tissues, and organs. The skin is a particularly attractive organ for the application of novel regenerative therapies due to its easy accessibility. Among these therapies, stem cells and platelet-rich plasma (PRP) have garnered interest based on their therapeutic potential in scar reduction, antiaging effects, and treatment of alopecia.

Stem cells possess the cardinal features of self-renewal and plasticity. Self-renewal refers to symmetric cell division generating daughter cells identical to the parent cell.¹ Plasticity is the ability to generate cell types other than the germ line or tissue lineage from which stem cells derive.² Stem cells can be categorized according to their differentiation potential. Totipotent stem cells may develop into any primary germ cell layer (ectoderm, mesoderm, endoderm) of the embryo, as well as extraembryonic tissue such as the trophoblast, which gives rise to the placenta. Pluripotent stem cells such as embryonic stem cells have the capacity to differentiate into any derivative of the 3 germ cell layers but have lost their ability to differentiate into the trophoblast.³ Adults lack totipotent or pluripotent cells; they have multipotent or unipotent cells. Multipotent stem cells are able to differentiate into multiple cell types from similar lineages; mesenchymal stem cells (MSCs), for example, can differentiate into adipogenic, osteogenic, chondrogenic, and myogenic cells.⁴ Unipotent stem cells have the lowest differentiation potential and can only self-regenerate. Herein, we review stem cell sources and their therapeutic potential in aesthetic dermatology.

Multipotent Stem Cells

Multipotent stem cells derived from the bone marrow, umbilical cord, adipose tissue, dermis, or hair follicle bulge have various clinical applications in dermatology. Stem cells from these sources are primarily utilized in an autologous manner in which they are processed outside the body and reintroduced into the donor. Autologous multipotent hematopoietic bone marrow cells were first successfully used for the treatment of chronic wounds and show promise for the treatment of atrophic scars.^5,6 However, due to the invasive nature of extracting bone marrow stem cells and their declining number with age, other sources of multipotent stem cells have fallen into favor.

Umbilical cord blood is a source of multipotent hematopoietic stem cells for which surgical intervention is not necessary because they are retrieved after umbilical cord clamping.⁷ Advantages of sourcing stem cells from umbilical cord blood includes high regenerative power compared to a newborn’s skin and low immunogenicity given that the newborn is immunologically immature.⁸

Another popular source for autologous stem cells is adipose tissue due to its ease of accessibility and relative abundance. Given that adipose tissue–derived stem cells (ASCs) are capable of differentiating into adipocytes that help maintain volume over time, they are being used for midface contouring, lip augmentation, facial rejuvenation, facial scarring, lipodystrophy, penile girth enhancement, and vaginal augmentation. Adipose tissue–derived stem cells also are capable of differentiating into other types of tissue, including cartilage and bone. Thus, they have been successfully harnessed in the treatment of patients affected by systemic sclerosis and Parry-Romberg syndrome as well in the functional and aesthetic reconstruction of various military combat–related deformities.^9,10

Adipose tissue–derived stem cells are commonly harvested from lipoaspirate of the abdomen and are combined with supportive mechanical scaffolds such as hydrogels. Lipoaspirate itself can serve as a scaffold for ASCs. Accordingly, ASCs also are being utilized as a scaffold for autologous fat transfer procedures in an effort to increase the viability of transplanted donor tissue, a process known as cell-assisted lipotransfer (CAL). In CAL, a fraction of the aspirated fat is processed for isolation of ASCs, which are then recombined with the remainder of the aspirated fat prior to grafting.¹¹ However, there is conflicting evidence as to whether CAL leads to improved graft success relative to conventional autologous fat transfer.^12,13

The skin also serves as an easily accessible and abundant autologous source of stem cells. A subtype of dermal fibroblasts has been proven to have multipotent potential.^14,15 These dermal fibroblasts are harvested from one area of the skin using punch biopsy and are processed and reinjected into another desired area of the skin.¹⁶ Autologous human fibroblasts have proven to be effective for the treatment of wrinkles, rhytides, and acne scars.¹⁷ In June 2011, the US Food and Drug Administration approved azficel-T, an autologous cellular product created by harvesting fibroblasts from a patient’s own postauricular skin, culture-expanding them in vitro for 3 months, and reinjecting the cells into the desired area of dermis in a series of treatments. This product was the first personalized cell therapy approved by the US Food and Drug Administration for aesthetic uses, specifically for the improvement of nasolabial fold wrinkles.¹⁸

In adults, hair follicles contain an area known as the bulge, which is a site rich in epithelial and melanocytic stem cells. Bulge stem cells have the ability to reproduce the interfollicular epidermis, hair follicle structures, and sebaceous glands, and they have been used to construct entirely new hair follicles in an artificial in vivo system.¹⁹ Sugiyama-Nakagiri et al²⁰ demonstrated that an entire hair follicle epithelium and interfollicular epidermis can be regenerated using cultured bulge stem cells. The cultured bulge stem cells were mixed with dermal papilla cells from neonatal rat vibrissae and engrafted into a silicone chamber implanted on the backs of severe combined immune deficient (SCID) mice. The grafts exhibited tufts of hair as well as a complete interfollicular epidermis at 4 weeks after transplantation.²⁰ Thus, these bulge stem cells have the potential to treat male androgenic alopecia and female pattern hair loss. Bulge stem cells also have been shown to accelerate wound healing.²¹ Additionally, autologous melanocytic stem cells located at the hair follicle bulge are effective for treating vitiligo and are being investigated for the treatment of hair graying.²²

Induced Pluripotent Stem Cells

Given the ethical concerns that surround the procurement and use of embryonic stem cells, efforts have been made to retrieve pluripotent stem cells from adults. A major breakthrough occurred in 2006 when researchers altered the genes of specialized adult mouse cells to cause dedifferentiation and the return to an embryoniclike stem cell state.²³ Mouse somatic cells were reprogrammed through the activation of a combination of transcription factors. The resulting cells were termed induced pluripotent stem cells (iPSCs) and have since been recreated in human cell lines. The discovery of iPSCs precipitated a translational science revolution. Physician-scientists sought ways to apply the reprogrammed cells to the pathophysiology of obscure diseases, examination of drug targets, and regeneration of human tissue.²⁴ Tissue regeneration via induced naïve somatic cells has shown promise as a future method to treat neurologic, cardiovascular, and ophthalmologic diseases.²⁵

As the technology of cultivating and identifying optimal sources of iPSCs continues to advance, stem cell–based treatments have evolved as leading prospects in the field of biogerontology.^26-29 Although much of the research in antiaging medicine has utilized iPSCs to reprogram cell senescence, the altering of iPSCs at a cellular level also allows for the stimulation of collagen synthesis. This potential for collagen generation may have direct applicability in dermatologic practice, particularly for aesthetic treatments.

Much of the research into iPSC-derived collagen has focused on genodermatoses. Itoh et al³⁰ examined the creation of collagen through iPSCs to identify possible treatments for recessive dystrophic epidermolysis bullosa (DEB). Recessive DEB is characterized by mutations in the COL7A1 gene, which encodes type VII collagen, a basement membrane protein and component of the anchoring fibrils essential for skin integrity.³¹ Itoh et al³⁰ began with source cells obtained from a skin biopsy. The cells were dedifferentiated to iPSCs and then induced into dermal fibroblasts according to the methods established in prior studies of embryonic stem cells, namely with the use of ascorbic acid and transforming growth factor b. The newly formed fibroblasts were determined to be functional based on their ability to synthesize mature type VII collagen.³⁰ Once the viability of the iPSC-derived fibroblasts was confirmed in vitro, the cells were further tested through combination with human keratinocytes on SCID mice. The human keratinocytes grew together with the iPSC-derived fibroblasts, producing type VII collagen in the basement membrane zone and creating an epidermis with the normal markers.³⁰ Similarly, Robbins et al³² utilized SCID mice to successfully demonstrate that the transfection of keratinocytes from patients with junctional epidermolysis bullosa into SCID mice produced phenotypically normal skin.

Sebastiano et al³³ combined the concepts of iPSCs and genome editing in another study of recessive DEB. The investigators first cultured iPSCs from biopsies of affected patients. After deriving iPSCs and correcting their mutation via adenovirus-associated viral gene editing, the COL7A1 mutation-free cells were differentiated into keratinocytes. These iPSC-derived keratinocytes were subsequently grafted onto mice, which led to the production of wild-type collagen VII and a stratified epidermis. Despite this successful outcome, the grafts of iPSC-derived epidermis did not survive longer than 1 month.³³

One of the many obstacles facing the practical use of stem cells is their successful incorporation into human tissue. A possible solution was uncovered by Zhang et al³⁴ who examined iPSC-derived MSCs. Mesenchymal stem cells communicate via paracrine mechanisms, whereby exosomes containing RNA and proteins are released to potentiate a regenerative effect.³⁵ Zhang et al³⁴ found that injecting exosomes from human iPSC-derived MSCs into the wound sites of rats stimulated the production of type I collagen, type III collagen, and elastin. The wound sites demonstrated accelerated closure, narrower scar widths, and increased collagen maturity.

Understanding the role that local environment plays in stem cell differentiation, Xu et al³⁶ aimed to create an extracellular scaffold to induce fibroblast behavior from iPSCs. The authors engineered a framework similar to the normal extracellular membrane using proteoglycans, glycosaminoglycans, fibrinogen, and connective tissue growth factor. The iPSCs were then applied to the scaffolding, which led to successful fibroblast differentiation and type I collagen synthesis.³⁶ This use of local biosignaling cues holds important ramifications for controlling the fate of stem cells that have been introduced into a new environment.

Although the application of iPSCs in clinical dermatology has yet to be achieved, progress in the field is moving at a rapid pace. Several logistical elements require further mastery before therapeutics can be delivered. These areas include the optimal environment for iPSC differentiation, methods for maximization of graft survival, and different modes of transplanting iPSC-derived cells into patients. In cosmetic practice, success will depend on intradermal injections of collagen-producing iPSC-derived cells that possess long-term proliferative potential. Current research in mice models has demonstrated viability up to 16 weeks after intradermal injection of such cells.³⁷

Plant Stem Cells

In discussing the dermatologic applications of stem cell technology, clinicians should be aware of the plant stem cell products that have become a popular cosmeceutical trend. Companies advertise plant cells as a natural source of regenerative cells that can induce rejuvenation in human skin; however, there are no significant data to indicate that plant stem cells encourage or activate cellular growth in humans. Indeed, for stem cells to differentiate and produce viable components, the cells must first be incorporated as living components in the host tissue. Because plant stem cells do not survive in human tissue and plant cell cytokines fail to interact with the receptors on human cells, their current value in cosmeceuticals may be overstated.

Platelet-Rich Plasma

Platelet-rich plasma also is commonly associated with stem cell therapy, as PRP is known to potentiate stem cell proliferation, migration, and differentiation. However, PRP does not contain stem cells and is instead autologous plasma concentrated with platelets. In fact, platelets cannot even be classified as cells given that they lack a nucleus; platelets are considered cell fragments. The regenerative potential of PRP can be attributed to the growth factors released from platelets, which play an important role in tissue regeneration and repair. Platelet-rich plasma currently is being used in dermatology for skin rejuvenation (reduction of wrinkles and furrows) and treatment of acne scars.³⁸ There also is evidence supporting the effectiveness of PRP for alopecia and wound therapy, as growth factors play a vital role in hair growth and wound healing.³⁸ Apart from the use of PRP on its own, it can be used as a supplement to enhance the effects of antiaging procedures such as microneedling.³⁹

Future Directions

Multipotent stem cells and iPSCs discussed herein provide much promise in the field of regenerative dermatology. They are increasingly accessible and circumvent the use of ethically questionable embryonic stem cells. Although there is a general consensus on the great potential of stem cells for treating aesthetic skin conditions, high-quality randomized controlled trials remain scarce within the literature. Recognizing and optimizing these opportunities remains the next step in the future delivery of evidence-based care in regenerative dermatology.

Background and Distribution

The Dermacentor ticks belong to the family Ixodidae (hard ticks). The 2 best-known ticks of the genus are Dermacentor andersoni (Rocky Mountain wood tick)(Figure, A) and Dermacentor variabilis (American dog tick)(Figure, B). The Dermacentor ticks are large ticks with small anterior mouthparts that attach to a rectangular basis capituli (Figure, A). Both ticks exhibit widely spaced eyes and posterior festoons as well as bifid coxa 1 (the attachment site for the first pair of legs) and enlarged coxa 4. As adults, these ticks display an ornate hard dorsal plate, or scutum, with numerous pits. Female ticks have a much smaller scutum, allowing for abdominal engorgement during feeding.¹ Although D andersoni tends to have a brown to yellow hue, the specimens of D variabilis display a somewhat silver color pattern.

Dermacentor ticks can be found throughout most of North America, with the northern distribution limits of both species previously occurring in the province of Saskatchewan, Canada. Although the range of D andersoni has remained relatively stable within this distribution, the distribution of D variabilis recently has expanded westward and northward of these limits.² The ranges of the 2 species overlap in certain areas, though D andersoni primarily is found in the Rocky Mountain and northwestern states as well as southwestern Canada, whereas D variabilis can be found throughout most parts of the United States, except in the Rocky Mountain states.³ Within these regions the ticks can be found in heavily wooded areas, but they most commonly inhabit fields with tall grass, crops, bushes, and shrubbery, often clustering where these types of vegetation form clearly defined edges.⁴ The diseases transmitted by the Dermacentor ticks include Rocky Mountain spotted fever (RMSF), Colorado tick fever, tularemia, tick paralysis, and even human monocytic erlichiosis, though Amblyomma americanum is the major vector for human monocytic erlichiosis.

Rocky Mountain Spotted Fever

Both species of ticks are known to serve as vectors for RMSF, but D variabilis is the major vector in the United States, especially in the eastern and southeastern parts of the United States. Overall, the majority of cases occur in North Carolina, South Carolina, Tennessee, and Oklahoma,⁵ with North Carolina having the highest incidence. In endemic areas, RMSF should be suspected in any patient with fever and headache, and empiric treatment with antibiotics should be started while awaiting the results of diagnostic tests. Serologic testing with indirect fluorescent antibodies is widely available and is considered the best method for detection; although the sensitivity is poor during the first 10 to 12 days of infection, it increases to 94% during days 14 to 21.⁶ Therapeutic decisions should be influenced by clinical suspicion and epidemiologic data. Treatment should be started promptly and should never be delayed until confirmatory tests are available. Doxycycline is considered the gold standard therapy in both adults and children, with a typical treatment duration of 10 days. The only other recommended agent for pregnant women in the first or second trimesters or patients with severe hypersensitivity reactions to tetracyclines is chloramphenicol.⁷

Colorado Tick Fever

Colorado tick fever, also known as mountain fever, is an arboviral infection transmitted by D andersoni. Its distribution coincides with the tick’s natural geographic range in the western United States and Rocky Mountains. Colorado tick fever causes an acute febrile illness consisting of chills, headaches, myalgia, retro-orbital pain, and malaise, which tend to occur within 3 to 5 days of the tick bite. Some cases may be accompanied by a nonspecific rash that may be morbilliform or petechial in appearance. Notably, approximately half of all patients will experience transient resolution of symptoms for 24 to 48 hours followed by a recurrence of fever, a phenomenon that has been referred to as saddleback fever. Routine laboratory findings may include leukopenia, thrombocytopenia, and a peripheral smear with atypical lymphocytes. Reverse transcription polymerase chain reaction is both sensitive and specific for detecting viral loads in the blood during the first week of infection, though testing does not alter management, which is largely supportive.⁸

Tularemia

Tularemia is a relatively rare disease but has been documented in every US state except Hawaii.⁹ The disease is caused by Francisella tularensis, a small, aerobic, gram-negative coccobacillus transmitted via inhalation, bitingflies, or tick bites; the most common ticks to transmit the disease include D andersoni, D variabilis, and A americanum.¹⁰ Clinical manifestations depend on the form of exposure, with tick bites most often resulting in an ulcerated skin lesion at the site of the vector bite accompanied by regional lymphadenopathy and systemic symptoms such as fever, chills, myalgia, and headache.¹¹ Mucosal manifestations such as pharyngitis, conjunctivitis, and other ocular lesions also are commonly seen. Diagnosis most frequently is made using serology because F tularensis is both challenging and dangerous to culture; in fact, because of the high risk of contagion, F tularensis should only be cultured in biosafety level 3 laboratories. Polymerase chain reaction assays can be used on tissue samples with decent sensitivity (78%) and specificity (96%); however, these assays cannot distinguish between Francisella subspecies and are not readily available to most clinicians.¹² First-line therapy for the treatment of tularemia is streptomycin given as twice-daily intramuscular injections over the course of 7 to 10 days. Alternative agents include gentamicin, ciprofloxacin, imipenem, doxycycline, and chloramphenicol.¹⁰ Because tularemia is relatively rare, a high index of suspicion is necessary to reduce the morbidity and mortality associated with the disease.

Tick Paralysis

More than 40 different species of ticks have been implicated worldwide as causes of tick paralysis, though D andersoni has been the most common in North America. Female patients account for most cases, possibly because long hair conceals ticks on the scalp or neck, the preferred attachment locations for Dermacentor ticks.¹³ The classic presentation of tick paralysis is an acute, flaccid, ascending paralysis that occurs from a neurotoxin in the tick saliva that impairs afferent nerve signal propagation.^14,15 The paralysis progresses over hours to days and typically occurs 5 to 6 days after attachment of the tick. Notably, there is no associated fever with tick paralysis, and without intervention, patients may die of respiratory failure. Overall, the condition carries a fatality rate of nearly 10%¹⁶ but reverses rapidly if the tick is identified and removed.

Protection against tick bites and tick-borne illnesses includes avoidance of infested areas, treatment of populated habitats with insecticide sprays, use of topical repellants prior to outdoor activities, and diligent full-body tick checks upon return from tick-heavy areas. Permethrin can be used to treat clothing and remains protective through multiple washings. Ticks typically survive washing of untreated clothing but are killed by prolonged drying in a dryer. Pets may be treated with oral, intramuscular, or topical agents prescribed by a veterinarian to prevent tick attachments.

Conclusion

Accurate identification of Dermacentor ticks allows for appropriate surveillance for associated diseases and can improve patient outcomes. Patients who engage in outdoor activities in endemic areas should take steps to avoid exposure, use appropriate acaricides and repellents, and perform tick checks after returning indoors.

Background and Distribution

The Dermacentor ticks belong to the family Ixodidae (hard ticks). The 2 best-known ticks of the genus are Dermacentor andersoni (Rocky Mountain wood tick)(Figure, A) and Dermacentor variabilis (American dog tick)(Figure, B). The Dermacentor ticks are large ticks with small anterior mouthparts that attach to a rectangular basis capituli (Figure, A). Both ticks exhibit widely spaced eyes and posterior festoons as well as bifid coxa 1 (the attachment site for the first pair of legs) and enlarged coxa 4. As adults, these ticks display an ornate hard dorsal plate, or scutum, with numerous pits. Female ticks have a much smaller scutum, allowing for abdominal engorgement during feeding.¹ Although D andersoni tends to have a brown to yellow hue, the specimens of D variabilis display a somewhat silver color pattern.

Dermacentor ticks can be found throughout most of North America, with the northern distribution limits of both species previously occurring in the province of Saskatchewan, Canada. Although the range of D andersoni has remained relatively stable within this distribution, the distribution of D variabilis recently has expanded westward and northward of these limits.² The ranges of the 2 species overlap in certain areas, though D andersoni primarily is found in the Rocky Mountain and northwestern states as well as southwestern Canada, whereas D variabilis can be found throughout most parts of the United States, except in the Rocky Mountain states.³ Within these regions the ticks can be found in heavily wooded areas, but they most commonly inhabit fields with tall grass, crops, bushes, and shrubbery, often clustering where these types of vegetation form clearly defined edges.⁴ The diseases transmitted by the Dermacentor ticks include Rocky Mountain spotted fever (RMSF), Colorado tick fever, tularemia, tick paralysis, and even human monocytic erlichiosis, though Amblyomma americanum is the major vector for human monocytic erlichiosis.

Rocky Mountain Spotted Fever

Both species of ticks are known to serve as vectors for RMSF, but D variabilis is the major vector in the United States, especially in the eastern and southeastern parts of the United States. Overall, the majority of cases occur in North Carolina, South Carolina, Tennessee, and Oklahoma,⁵ with North Carolina having the highest incidence. In endemic areas, RMSF should be suspected in any patient with fever and headache, and empiric treatment with antibiotics should be started while awaiting the results of diagnostic tests. Serologic testing with indirect fluorescent antibodies is widely available and is considered the best method for detection; although the sensitivity is poor during the first 10 to 12 days of infection, it increases to 94% during days 14 to 21.⁶ Therapeutic decisions should be influenced by clinical suspicion and epidemiologic data. Treatment should be started promptly and should never be delayed until confirmatory tests are available. Doxycycline is considered the gold standard therapy in both adults and children, with a typical treatment duration of 10 days. The only other recommended agent for pregnant women in the first or second trimesters or patients with severe hypersensitivity reactions to tetracyclines is chloramphenicol.⁷

Colorado Tick Fever

Colorado tick fever, also known as mountain fever, is an arboviral infection transmitted by D andersoni. Its distribution coincides with the tick’s natural geographic range in the western United States and Rocky Mountains. Colorado tick fever causes an acute febrile illness consisting of chills, headaches, myalgia, retro-orbital pain, and malaise, which tend to occur within 3 to 5 days of the tick bite. Some cases may be accompanied by a nonspecific rash that may be morbilliform or petechial in appearance. Notably, approximately half of all patients will experience transient resolution of symptoms for 24 to 48 hours followed by a recurrence of fever, a phenomenon that has been referred to as saddleback fever. Routine laboratory findings may include leukopenia, thrombocytopenia, and a peripheral smear with atypical lymphocytes. Reverse transcription polymerase chain reaction is both sensitive and specific for detecting viral loads in the blood during the first week of infection, though testing does not alter management, which is largely supportive.⁸

Tularemia

Tularemia is a relatively rare disease but has been documented in every US state except Hawaii.⁹ The disease is caused by Francisella tularensis, a small, aerobic, gram-negative coccobacillus transmitted via inhalation, bitingflies, or tick bites; the most common ticks to transmit the disease include D andersoni, D variabilis, and A americanum.¹⁰ Clinical manifestations depend on the form of exposure, with tick bites most often resulting in an ulcerated skin lesion at the site of the vector bite accompanied by regional lymphadenopathy and systemic symptoms such as fever, chills, myalgia, and headache.¹¹ Mucosal manifestations such as pharyngitis, conjunctivitis, and other ocular lesions also are commonly seen. Diagnosis most frequently is made using serology because F tularensis is both challenging and dangerous to culture; in fact, because of the high risk of contagion, F tularensis should only be cultured in biosafety level 3 laboratories. Polymerase chain reaction assays can be used on tissue samples with decent sensitivity (78%) and specificity (96%); however, these assays cannot distinguish between Francisella subspecies and are not readily available to most clinicians.¹² First-line therapy for the treatment of tularemia is streptomycin given as twice-daily intramuscular injections over the course of 7 to 10 days. Alternative agents include gentamicin, ciprofloxacin, imipenem, doxycycline, and chloramphenicol.¹⁰ Because tularemia is relatively rare, a high index of suspicion is necessary to reduce the morbidity and mortality associated with the disease.

Tick Paralysis

More than 40 different species of ticks have been implicated worldwide as causes of tick paralysis, though D andersoni has been the most common in North America. Female patients account for most cases, possibly because long hair conceals ticks on the scalp or neck, the preferred attachment locations for Dermacentor ticks.¹³ The classic presentation of tick paralysis is an acute, flaccid, ascending paralysis that occurs from a neurotoxin in the tick saliva that impairs afferent nerve signal propagation.^14,15 The paralysis progresses over hours to days and typically occurs 5 to 6 days after attachment of the tick. Notably, there is no associated fever with tick paralysis, and without intervention, patients may die of respiratory failure. Overall, the condition carries a fatality rate of nearly 10%¹⁶ but reverses rapidly if the tick is identified and removed.

Protection against tick bites and tick-borne illnesses includes avoidance of infested areas, treatment of populated habitats with insecticide sprays, use of topical repellants prior to outdoor activities, and diligent full-body tick checks upon return from tick-heavy areas. Permethrin can be used to treat clothing and remains protective through multiple washings. Ticks typically survive washing of untreated clothing but are killed by prolonged drying in a dryer. Pets may be treated with oral, intramuscular, or topical agents prescribed by a veterinarian to prevent tick attachments.

Conclusion

Accurate identification of Dermacentor ticks allows for appropriate surveillance for associated diseases and can improve patient outcomes. Patients who engage in outdoor activities in endemic areas should take steps to avoid exposure, use appropriate acaricides and repellents, and perform tick checks after returning indoors.

Background and Distribution

The Dermacentor ticks belong to the family Ixodidae (hard ticks). The 2 best-known ticks of the genus are Dermacentor andersoni (Rocky Mountain wood tick)(Figure, A) and Dermacentor variabilis (American dog tick)(Figure, B). The Dermacentor ticks are large ticks with small anterior mouthparts that attach to a rectangular basis capituli (Figure, A). Both ticks exhibit widely spaced eyes and posterior festoons as well as bifid coxa 1 (the attachment site for the first pair of legs) and enlarged coxa 4. As adults, these ticks display an ornate hard dorsal plate, or scutum, with numerous pits. Female ticks have a much smaller scutum, allowing for abdominal engorgement during feeding.¹ Although D andersoni tends to have a brown to yellow hue, the specimens of D variabilis display a somewhat silver color pattern.

Dermacentor ticks can be found throughout most of North America, with the northern distribution limits of both species previously occurring in the province of Saskatchewan, Canada. Although the range of D andersoni has remained relatively stable within this distribution, the distribution of D variabilis recently has expanded westward and northward of these limits.² The ranges of the 2 species overlap in certain areas, though D andersoni primarily is found in the Rocky Mountain and northwestern states as well as southwestern Canada, whereas D variabilis can be found throughout most parts of the United States, except in the Rocky Mountain states.³ Within these regions the ticks can be found in heavily wooded areas, but they most commonly inhabit fields with tall grass, crops, bushes, and shrubbery, often clustering where these types of vegetation form clearly defined edges.⁴ The diseases transmitted by the Dermacentor ticks include Rocky Mountain spotted fever (RMSF), Colorado tick fever, tularemia, tick paralysis, and even human monocytic erlichiosis, though Amblyomma americanum is the major vector for human monocytic erlichiosis.

Rocky Mountain Spotted Fever

Both species of ticks are known to serve as vectors for RMSF, but D variabilis is the major vector in the United States, especially in the eastern and southeastern parts of the United States. Overall, the majority of cases occur in North Carolina, South Carolina, Tennessee, and Oklahoma,⁵ with North Carolina having the highest incidence. In endemic areas, RMSF should be suspected in any patient with fever and headache, and empiric treatment with antibiotics should be started while awaiting the results of diagnostic tests. Serologic testing with indirect fluorescent antibodies is widely available and is considered the best method for detection; although the sensitivity is poor during the first 10 to 12 days of infection, it increases to 94% during days 14 to 21.⁶ Therapeutic decisions should be influenced by clinical suspicion and epidemiologic data. Treatment should be started promptly and should never be delayed until confirmatory tests are available. Doxycycline is considered the gold standard therapy in both adults and children, with a typical treatment duration of 10 days. The only other recommended agent for pregnant women in the first or second trimesters or patients with severe hypersensitivity reactions to tetracyclines is chloramphenicol.⁷

Colorado Tick Fever

Colorado tick fever, also known as mountain fever, is an arboviral infection transmitted by D andersoni. Its distribution coincides with the tick’s natural geographic range in the western United States and Rocky Mountains. Colorado tick fever causes an acute febrile illness consisting of chills, headaches, myalgia, retro-orbital pain, and malaise, which tend to occur within 3 to 5 days of the tick bite. Some cases may be accompanied by a nonspecific rash that may be morbilliform or petechial in appearance. Notably, approximately half of all patients will experience transient resolution of symptoms for 24 to 48 hours followed by a recurrence of fever, a phenomenon that has been referred to as saddleback fever. Routine laboratory findings may include leukopenia, thrombocytopenia, and a peripheral smear with atypical lymphocytes. Reverse transcription polymerase chain reaction is both sensitive and specific for detecting viral loads in the blood during the first week of infection, though testing does not alter management, which is largely supportive.⁸

Tularemia

Tularemia is a relatively rare disease but has been documented in every US state except Hawaii.⁹ The disease is caused by Francisella tularensis, a small, aerobic, gram-negative coccobacillus transmitted via inhalation, bitingflies, or tick bites; the most common ticks to transmit the disease include D andersoni, D variabilis, and A americanum.¹⁰ Clinical manifestations depend on the form of exposure, with tick bites most often resulting in an ulcerated skin lesion at the site of the vector bite accompanied by regional lymphadenopathy and systemic symptoms such as fever, chills, myalgia, and headache.¹¹ Mucosal manifestations such as pharyngitis, conjunctivitis, and other ocular lesions also are commonly seen. Diagnosis most frequently is made using serology because F tularensis is both challenging and dangerous to culture; in fact, because of the high risk of contagion, F tularensis should only be cultured in biosafety level 3 laboratories. Polymerase chain reaction assays can be used on tissue samples with decent sensitivity (78%) and specificity (96%); however, these assays cannot distinguish between Francisella subspecies and are not readily available to most clinicians.¹² First-line therapy for the treatment of tularemia is streptomycin given as twice-daily intramuscular injections over the course of 7 to 10 days. Alternative agents include gentamicin, ciprofloxacin, imipenem, doxycycline, and chloramphenicol.¹⁰ Because tularemia is relatively rare, a high index of suspicion is necessary to reduce the morbidity and mortality associated with the disease.

Tick Paralysis

More than 40 different species of ticks have been implicated worldwide as causes of tick paralysis, though D andersoni has been the most common in North America. Female patients account for most cases, possibly because long hair conceals ticks on the scalp or neck, the preferred attachment locations for Dermacentor ticks.¹³ The classic presentation of tick paralysis is an acute, flaccid, ascending paralysis that occurs from a neurotoxin in the tick saliva that impairs afferent nerve signal propagation.^14,15 The paralysis progresses over hours to days and typically occurs 5 to 6 days after attachment of the tick. Notably, there is no associated fever with tick paralysis, and without intervention, patients may die of respiratory failure. Overall, the condition carries a fatality rate of nearly 10%¹⁶ but reverses rapidly if the tick is identified and removed.

Protection against tick bites and tick-borne illnesses includes avoidance of infested areas, treatment of populated habitats with insecticide sprays, use of topical repellants prior to outdoor activities, and diligent full-body tick checks upon return from tick-heavy areas. Permethrin can be used to treat clothing and remains protective through multiple washings. Ticks typically survive washing of untreated clothing but are killed by prolonged drying in a dryer. Pets may be treated with oral, intramuscular, or topical agents prescribed by a veterinarian to prevent tick attachments.

Conclusion

Accurate identification of Dermacentor ticks allows for appropriate surveillance for associated diseases and can improve patient outcomes. Patients who engage in outdoor activities in endemic areas should take steps to avoid exposure, use appropriate acaricides and repellents, and perform tick checks after returning indoors.