Mary Lien, MD

To the Editor:

A 56-year-old white woman with a history of melanoma and hypertension presented for evaluation of progressive hair loss of more than 1 year’s duration with associated pruritis. Scalp examination revealed diffuse erythema and scarring alopecia of the bilateral parietal and temporal regions. Physical examination also revealed nonscarring alopecia of the bilateral axillae, with associated thinning of the pubic hair, eyebrows, and eyelashes, as well as keratosis pilaris on the upper arms. Biopsy of the parietal scalp revealed mild scarring alopecia with isthmic fibroplasia consistent with early lichen planopilaris (LPP)(Figure). These histologic features combined with the patient’s clinical presentation were consistent with a diagnosis of Graham-Little-Piccardi-Lassueur syndrome (GLPL).

Graham-Little-Piccardi-Lassueur syndrome was first described by Piccardi in 1913.A second case was then described by Graham-Little in 1915 in a patient referred by Lassueur, resulting in the name it bears today.^1,2 The condition presents most commonly in middle-aged white women and is characterized by a triad of cicatricial alopecia of the scalp, nonscarring alopecia of the axillae and/or groin, and a rough follicular eruption on the body and/or scalp. Symptoms may not be present simultaneously. In GLPL, scarring alopecia of the scalp often precedes follicular eruptions of the trunk, arms, and legs by as much as years,² and the inverse also has been reported.¹ The inflammatory lesions of the scalp eventually resolve spontaneously, but the hair loss is by definition irreversible.

This rare condition is considered one of the 3 clinical variants of LPP. Other variants include classic LPP, also known as follicular lichen planus, and frontal fibrosing alopecia.³ More recently, fibrosing alopecia in a pattern distribution has gained some popularity as a fourth variant of LPP.⁴ All variants of LPP, including GLPL, result in a scarring alopecia. The classic scalp finding is an erythematous to violaceous, perifollicular, hyperkeratotic scale at the base of the terminal hairs. The population of inflamed follicles spreads outward, leaving behind a round to oval, central, atrophic scar that often is devoid of follicles. Few hairs may persist within zones of alopecia at presentation; however, these hairs are affected by inflammation and also will likely shed. A hair pull test will be positive at the margins during active disease, consisting of mostly anagen hairs on trichogram examination.^1,5 Patients may develop only a single foci of hair loss, but much more commonly, a patchy multifocal alopecia is noted.⁶ Sites often will coalesce. Onset of scalp alopecia may be insidious or fulminant.

The nonscarring alopecia of the axillae and groin may be described as subtle thinning to complete hair loss with no signs of atrophy or inflammation. Although not commonly reported, a case of nonscarring alopecia located on the shoulders has been seen.⁷

The follicular eruption that can be present on the trunk, arms, or legs in GLPL is most often but not limited to keratosis pilaris, as was seen in our patient. One reported case also described lichen spinulosus as a potential variant.⁸ Lichen planopilaris is separate from lichen planus (LP) because of its selective follicular involvement vs the nonselective mucocutaneous distribution of LP. The 2 processes also are histologically distinct; however, estimations have shown that more than 50% of patients with GLPL experience at least 1 episode of mucosal or cutaneous LP in their lifetime.⁹ Rarely, coexistence of GLPL and LP lesions has been described. One reported case of GLPL and concomitant hypertrophic LP could represent a severe form of the disease.⁹ Additionally, lichen planus pigmentosus, an uncommon variant of LP characterized by hyperpigmented brown macules in sun-exposed areas and flexural folds, was identified in a case report of an Asian woman with GLPL.¹⁰

As a general rule, the variants of LPP most commonly are seen in postmenopausal women aged 40 to 60 years; however, rare cases in a child and a teenager have been reported.¹¹ The GLPL variant of LPP is reported up to 4 times more frequently in females.⁵ Pruritus and pain are inconsistent findings, and there are no systemic signs of illness. A case of androgen insensitivity syndrome associated with GLPL suggested a potential influence of hormones in LPP.¹² Stress, vitamin A deficiency, and autoimmunity also have been proposed as triggers of GLPL.¹³ Furthermore, familial GLPL was described in a mother and daughter, though the association was uncertain.¹⁴ Our patient had no relevant family history.

Workups to reveal the etiology of GLPL have been inconclusive. Reports of laboratory testing including complete blood cell count, basic metabolic panel, liver function tests, testosterone and dehydroepiandrosterone levels, and chest radiograph have been normal.² Additional workup for viral triggers also has been negative.¹⁵ A case series of 29 patients with LPP and its variants, including GLPL, revealed positive antinuclear antibodies in 10% of patients and a thyroid disorder in 24% of patients, with Hashimoto thyroiditis being the most prevalent in 7% of cases.¹⁶ There may be a strong association between the comorbidities of thyroid dysfunction and GLPL, as documented in other studies.^10,17 A case-control study by Mesinkovska et al¹⁷ revealed a considerable increase in the prevalence of thyroid gland disease among patients with LPP vs controls. Human leukocyte antigen DR1 was found in a familial case of GLPL,⁴ and a case of GLPL following hepatitis B vaccination also has been described.¹⁸

Graham-Little-Piccardi-Lassueur syndrome most likely is a T-cell mediated autoimmune condition associated with one or multiple unknown keratinocyte antigens. Autoantibodies to the inner centromere protein were identified in a case that was positive on direct immunofluorescence, which may provide more insight into the disease pathophysiology.¹³ Interestingly, a study comparing the concentrations of inflammatory cells in LPP and traction alopecia found an elevation in the ratio of Langerhans cells to T lymphocytes within the follicular inflammatory infiltrate of LPP.¹⁹

Because the number of patients with GLPL is so few, therapy should mirror advances being made in treatments for other variants of LPP. More recent studies of LPP treatment with hydroxychloroquine showed opposing results, though the safety profile of this agent makes it an enticing treatment option.^22,23 Tetracyclines showed improvement in 4 of 15 (26.7%) patients in a retrospective study by Spencer et al.²⁴ Another retrospective study showed promising results with the potent 5-alpha reductase inhibitor dutasteride with 7 of 10 (70%) postmenopausal patients reporting stabilization over a mean duration of 28 months with no reported side effects.²⁵ Antimalarial medications also have been implemented as adjunct therapies with mixed results.⁵ A case of a 26-year-old man with GLPL from South India showed systemic disease improvement following treatment with pulsed systemic steroids, isotretinoin, and anxiolytics.⁷ Chloroquine phosphate at a daily dose of 150 mg for 3 to 9 months yielded a transient response in one postmenopausal patient with frontal fibrosing alopecia.⁶ Stabilization of hair loss was achieved with a combination of hydroxychloroquine and doxycycline in a woman with GLPL who was previously unresponsive to tacrolimus ointment.¹⁰ Thalidomide showed early promise in an isolated report claiming successful treatment of LPP,²⁶ but there is contradictory evidence, as thalidomide showed no benefit in a series of 4 patients with LPP.²⁷

Peroxisome proliferator–activated receptor gamma (PPAR-γ), a transcription factor that regulates genes, is downregulated in LPP.²⁸ Deletion of PPAR-γ within follicular stem cells in mice results in a phenotype similar to cicatricial alopecia. Data have supported the role of PPAR-γ in maintaining the pilosebaceous unit. A case report of pioglitazone (PPAR-γ agonist) therapy used at 15 mg daily for 8 months was successful in treating a patient with LPP.²⁸ Further investigation must be conducted to evaluate these treatments since early attenuation of the disease process is crucial to the reduction of permanent hair loss.

Advances in the early recognition and successful treatment of GLPL are dependent on continued research in all variants of LPP. Randomized controlled trials are necessary to establish standard of care. Further studies should target the association of GLPL and other autoimmune phenomena. Moreover, research into the etiology will provide direction in understanding disease progression and outcome.

To the Editor:

A 56-year-old white woman with a history of melanoma and hypertension presented for evaluation of progressive hair loss of more than 1 year’s duration with associated pruritis. Scalp examination revealed diffuse erythema and scarring alopecia of the bilateral parietal and temporal regions. Physical examination also revealed nonscarring alopecia of the bilateral axillae, with associated thinning of the pubic hair, eyebrows, and eyelashes, as well as keratosis pilaris on the upper arms. Biopsy of the parietal scalp revealed mild scarring alopecia with isthmic fibroplasia consistent with early lichen planopilaris (LPP)(Figure). These histologic features combined with the patient’s clinical presentation were consistent with a diagnosis of Graham-Little-Piccardi-Lassueur syndrome (GLPL).

Graham-Little-Piccardi-Lassueur syndrome was first described by Piccardi in 1913.A second case was then described by Graham-Little in 1915 in a patient referred by Lassueur, resulting in the name it bears today.^1,2 The condition presents most commonly in middle-aged white women and is characterized by a triad of cicatricial alopecia of the scalp, nonscarring alopecia of the axillae and/or groin, and a rough follicular eruption on the body and/or scalp. Symptoms may not be present simultaneously. In GLPL, scarring alopecia of the scalp often precedes follicular eruptions of the trunk, arms, and legs by as much as years,² and the inverse also has been reported.¹ The inflammatory lesions of the scalp eventually resolve spontaneously, but the hair loss is by definition irreversible.

This rare condition is considered one of the 3 clinical variants of LPP. Other variants include classic LPP, also known as follicular lichen planus, and frontal fibrosing alopecia.³ More recently, fibrosing alopecia in a pattern distribution has gained some popularity as a fourth variant of LPP.⁴ All variants of LPP, including GLPL, result in a scarring alopecia. The classic scalp finding is an erythematous to violaceous, perifollicular, hyperkeratotic scale at the base of the terminal hairs. The population of inflamed follicles spreads outward, leaving behind a round to oval, central, atrophic scar that often is devoid of follicles. Few hairs may persist within zones of alopecia at presentation; however, these hairs are affected by inflammation and also will likely shed. A hair pull test will be positive at the margins during active disease, consisting of mostly anagen hairs on trichogram examination.^1,5 Patients may develop only a single foci of hair loss, but much more commonly, a patchy multifocal alopecia is noted.⁶ Sites often will coalesce. Onset of scalp alopecia may be insidious or fulminant.

The nonscarring alopecia of the axillae and groin may be described as subtle thinning to complete hair loss with no signs of atrophy or inflammation. Although not commonly reported, a case of nonscarring alopecia located on the shoulders has been seen.⁷

The follicular eruption that can be present on the trunk, arms, or legs in GLPL is most often but not limited to keratosis pilaris, as was seen in our patient. One reported case also described lichen spinulosus as a potential variant.⁸ Lichen planopilaris is separate from lichen planus (LP) because of its selective follicular involvement vs the nonselective mucocutaneous distribution of LP. The 2 processes also are histologically distinct; however, estimations have shown that more than 50% of patients with GLPL experience at least 1 episode of mucosal or cutaneous LP in their lifetime.⁹ Rarely, coexistence of GLPL and LP lesions has been described. One reported case of GLPL and concomitant hypertrophic LP could represent a severe form of the disease.⁹ Additionally, lichen planus pigmentosus, an uncommon variant of LP characterized by hyperpigmented brown macules in sun-exposed areas and flexural folds, was identified in a case report of an Asian woman with GLPL.¹⁰

As a general rule, the variants of LPP most commonly are seen in postmenopausal women aged 40 to 60 years; however, rare cases in a child and a teenager have been reported.¹¹ The GLPL variant of LPP is reported up to 4 times more frequently in females.⁵ Pruritus and pain are inconsistent findings, and there are no systemic signs of illness. A case of androgen insensitivity syndrome associated with GLPL suggested a potential influence of hormones in LPP.¹² Stress, vitamin A deficiency, and autoimmunity also have been proposed as triggers of GLPL.¹³ Furthermore, familial GLPL was described in a mother and daughter, though the association was uncertain.¹⁴ Our patient had no relevant family history.

Workups to reveal the etiology of GLPL have been inconclusive. Reports of laboratory testing including complete blood cell count, basic metabolic panel, liver function tests, testosterone and dehydroepiandrosterone levels, and chest radiograph have been normal.² Additional workup for viral triggers also has been negative.¹⁵ A case series of 29 patients with LPP and its variants, including GLPL, revealed positive antinuclear antibodies in 10% of patients and a thyroid disorder in 24% of patients, with Hashimoto thyroiditis being the most prevalent in 7% of cases.¹⁶ There may be a strong association between the comorbidities of thyroid dysfunction and GLPL, as documented in other studies.^10,17 A case-control study by Mesinkovska et al¹⁷ revealed a considerable increase in the prevalence of thyroid gland disease among patients with LPP vs controls. Human leukocyte antigen DR1 was found in a familial case of GLPL,⁴ and a case of GLPL following hepatitis B vaccination also has been described.¹⁸

Graham-Little-Piccardi-Lassueur syndrome most likely is a T-cell mediated autoimmune condition associated with one or multiple unknown keratinocyte antigens. Autoantibodies to the inner centromere protein were identified in a case that was positive on direct immunofluorescence, which may provide more insight into the disease pathophysiology.¹³ Interestingly, a study comparing the concentrations of inflammatory cells in LPP and traction alopecia found an elevation in the ratio of Langerhans cells to T lymphocytes within the follicular inflammatory infiltrate of LPP.¹⁹

Because the number of patients with GLPL is so few, therapy should mirror advances being made in treatments for other variants of LPP. More recent studies of LPP treatment with hydroxychloroquine showed opposing results, though the safety profile of this agent makes it an enticing treatment option.^22,23 Tetracyclines showed improvement in 4 of 15 (26.7%) patients in a retrospective study by Spencer et al.²⁴ Another retrospective study showed promising results with the potent 5-alpha reductase inhibitor dutasteride with 7 of 10 (70%) postmenopausal patients reporting stabilization over a mean duration of 28 months with no reported side effects.²⁵ Antimalarial medications also have been implemented as adjunct therapies with mixed results.⁵ A case of a 26-year-old man with GLPL from South India showed systemic disease improvement following treatment with pulsed systemic steroids, isotretinoin, and anxiolytics.⁷ Chloroquine phosphate at a daily dose of 150 mg for 3 to 9 months yielded a transient response in one postmenopausal patient with frontal fibrosing alopecia.⁶ Stabilization of hair loss was achieved with a combination of hydroxychloroquine and doxycycline in a woman with GLPL who was previously unresponsive to tacrolimus ointment.¹⁰ Thalidomide showed early promise in an isolated report claiming successful treatment of LPP,²⁶ but there is contradictory evidence, as thalidomide showed no benefit in a series of 4 patients with LPP.²⁷

Peroxisome proliferator–activated receptor gamma (PPAR-γ), a transcription factor that regulates genes, is downregulated in LPP.²⁸ Deletion of PPAR-γ within follicular stem cells in mice results in a phenotype similar to cicatricial alopecia. Data have supported the role of PPAR-γ in maintaining the pilosebaceous unit. A case report of pioglitazone (PPAR-γ agonist) therapy used at 15 mg daily for 8 months was successful in treating a patient with LPP.²⁸ Further investigation must be conducted to evaluate these treatments since early attenuation of the disease process is crucial to the reduction of permanent hair loss.

Advances in the early recognition and successful treatment of GLPL are dependent on continued research in all variants of LPP. Randomized controlled trials are necessary to establish standard of care. Further studies should target the association of GLPL and other autoimmune phenomena. Moreover, research into the etiology will provide direction in understanding disease progression and outcome.

To the Editor:

A 56-year-old white woman with a history of melanoma and hypertension presented for evaluation of progressive hair loss of more than 1 year’s duration with associated pruritis. Scalp examination revealed diffuse erythema and scarring alopecia of the bilateral parietal and temporal regions. Physical examination also revealed nonscarring alopecia of the bilateral axillae, with associated thinning of the pubic hair, eyebrows, and eyelashes, as well as keratosis pilaris on the upper arms. Biopsy of the parietal scalp revealed mild scarring alopecia with isthmic fibroplasia consistent with early lichen planopilaris (LPP)(Figure). These histologic features combined with the patient’s clinical presentation were consistent with a diagnosis of Graham-Little-Piccardi-Lassueur syndrome (GLPL).

Graham-Little-Piccardi-Lassueur syndrome was first described by Piccardi in 1913.A second case was then described by Graham-Little in 1915 in a patient referred by Lassueur, resulting in the name it bears today.^1,2 The condition presents most commonly in middle-aged white women and is characterized by a triad of cicatricial alopecia of the scalp, nonscarring alopecia of the axillae and/or groin, and a rough follicular eruption on the body and/or scalp. Symptoms may not be present simultaneously. In GLPL, scarring alopecia of the scalp often precedes follicular eruptions of the trunk, arms, and legs by as much as years,² and the inverse also has been reported.¹ The inflammatory lesions of the scalp eventually resolve spontaneously, but the hair loss is by definition irreversible.

This rare condition is considered one of the 3 clinical variants of LPP. Other variants include classic LPP, also known as follicular lichen planus, and frontal fibrosing alopecia.³ More recently, fibrosing alopecia in a pattern distribution has gained some popularity as a fourth variant of LPP.⁴ All variants of LPP, including GLPL, result in a scarring alopecia. The classic scalp finding is an erythematous to violaceous, perifollicular, hyperkeratotic scale at the base of the terminal hairs. The population of inflamed follicles spreads outward, leaving behind a round to oval, central, atrophic scar that often is devoid of follicles. Few hairs may persist within zones of alopecia at presentation; however, these hairs are affected by inflammation and also will likely shed. A hair pull test will be positive at the margins during active disease, consisting of mostly anagen hairs on trichogram examination.^1,5 Patients may develop only a single foci of hair loss, but much more commonly, a patchy multifocal alopecia is noted.⁶ Sites often will coalesce. Onset of scalp alopecia may be insidious or fulminant.

The nonscarring alopecia of the axillae and groin may be described as subtle thinning to complete hair loss with no signs of atrophy or inflammation. Although not commonly reported, a case of nonscarring alopecia located on the shoulders has been seen.⁷

The follicular eruption that can be present on the trunk, arms, or legs in GLPL is most often but not limited to keratosis pilaris, as was seen in our patient. One reported case also described lichen spinulosus as a potential variant.⁸ Lichen planopilaris is separate from lichen planus (LP) because of its selective follicular involvement vs the nonselective mucocutaneous distribution of LP. The 2 processes also are histologically distinct; however, estimations have shown that more than 50% of patients with GLPL experience at least 1 episode of mucosal or cutaneous LP in their lifetime.⁹ Rarely, coexistence of GLPL and LP lesions has been described. One reported case of GLPL and concomitant hypertrophic LP could represent a severe form of the disease.⁹ Additionally, lichen planus pigmentosus, an uncommon variant of LP characterized by hyperpigmented brown macules in sun-exposed areas and flexural folds, was identified in a case report of an Asian woman with GLPL.¹⁰

As a general rule, the variants of LPP most commonly are seen in postmenopausal women aged 40 to 60 years; however, rare cases in a child and a teenager have been reported.¹¹ The GLPL variant of LPP is reported up to 4 times more frequently in females.⁵ Pruritus and pain are inconsistent findings, and there are no systemic signs of illness. A case of androgen insensitivity syndrome associated with GLPL suggested a potential influence of hormones in LPP.¹² Stress, vitamin A deficiency, and autoimmunity also have been proposed as triggers of GLPL.¹³ Furthermore, familial GLPL was described in a mother and daughter, though the association was uncertain.¹⁴ Our patient had no relevant family history.

Workups to reveal the etiology of GLPL have been inconclusive. Reports of laboratory testing including complete blood cell count, basic metabolic panel, liver function tests, testosterone and dehydroepiandrosterone levels, and chest radiograph have been normal.² Additional workup for viral triggers also has been negative.¹⁵ A case series of 29 patients with LPP and its variants, including GLPL, revealed positive antinuclear antibodies in 10% of patients and a thyroid disorder in 24% of patients, with Hashimoto thyroiditis being the most prevalent in 7% of cases.¹⁶ There may be a strong association between the comorbidities of thyroid dysfunction and GLPL, as documented in other studies.^10,17 A case-control study by Mesinkovska et al¹⁷ revealed a considerable increase in the prevalence of thyroid gland disease among patients with LPP vs controls. Human leukocyte antigen DR1 was found in a familial case of GLPL,⁴ and a case of GLPL following hepatitis B vaccination also has been described.¹⁸

Graham-Little-Piccardi-Lassueur syndrome most likely is a T-cell mediated autoimmune condition associated with one or multiple unknown keratinocyte antigens. Autoantibodies to the inner centromere protein were identified in a case that was positive on direct immunofluorescence, which may provide more insight into the disease pathophysiology.¹³ Interestingly, a study comparing the concentrations of inflammatory cells in LPP and traction alopecia found an elevation in the ratio of Langerhans cells to T lymphocytes within the follicular inflammatory infiltrate of LPP.¹⁹

Because the number of patients with GLPL is so few, therapy should mirror advances being made in treatments for other variants of LPP. More recent studies of LPP treatment with hydroxychloroquine showed opposing results, though the safety profile of this agent makes it an enticing treatment option.^22,23 Tetracyclines showed improvement in 4 of 15 (26.7%) patients in a retrospective study by Spencer et al.²⁴ Another retrospective study showed promising results with the potent 5-alpha reductase inhibitor dutasteride with 7 of 10 (70%) postmenopausal patients reporting stabilization over a mean duration of 28 months with no reported side effects.²⁵ Antimalarial medications also have been implemented as adjunct therapies with mixed results.⁵ A case of a 26-year-old man with GLPL from South India showed systemic disease improvement following treatment with pulsed systemic steroids, isotretinoin, and anxiolytics.⁷ Chloroquine phosphate at a daily dose of 150 mg for 3 to 9 months yielded a transient response in one postmenopausal patient with frontal fibrosing alopecia.⁶ Stabilization of hair loss was achieved with a combination of hydroxychloroquine and doxycycline in a woman with GLPL who was previously unresponsive to tacrolimus ointment.¹⁰ Thalidomide showed early promise in an isolated report claiming successful treatment of LPP,²⁶ but there is contradictory evidence, as thalidomide showed no benefit in a series of 4 patients with LPP.²⁷

Peroxisome proliferator–activated receptor gamma (PPAR-γ), a transcription factor that regulates genes, is downregulated in LPP.²⁸ Deletion of PPAR-γ within follicular stem cells in mice results in a phenotype similar to cicatricial alopecia. Data have supported the role of PPAR-γ in maintaining the pilosebaceous unit. A case report of pioglitazone (PPAR-γ agonist) therapy used at 15 mg daily for 8 months was successful in treating a patient with LPP.²⁸ Further investigation must be conducted to evaluate these treatments since early attenuation of the disease process is crucial to the reduction of permanent hair loss.

Advances in the early recognition and successful treatment of GLPL are dependent on continued research in all variants of LPP. Randomized controlled trials are necessary to establish standard of care. Further studies should target the association of GLPL and other autoimmune phenomena. Moreover, research into the etiology will provide direction in understanding disease progression and outcome.

In 1931, Lindberg¹ described a cutaneous variant of polyarteritis nodosa, which lacked visceral involvement and possessed a more favorable prognosis.² Cutaneous polyarteritis nodosa (CPAN) is a localized small- to medium-vessel vasculitis restricted to the skin. Both benign and chronic courses have been described, and systemic involvement does not occur.³ Diagnostic criteria proposed by Nakamura et al³ in 2009 included cutaneous nodules, livedo reticularis, purpura, or ulcers; histopathologic fibrinoid necrotizing vasculitis of small- to medium-sized vessels; and exclusion of systemic symptoms (eg, fever, hypertension, weight loss, renal failure, cerebral hemorrhage, neuropathy, myocardial infarction, ischemic heart disease, pericarditis, pleuritis, arthralgia/myalgia). Nodules occur in 30% to 50% of cases and can remain for years if left untreated. Ulcerations occur in up to 30% of patients. Myositis, arthritis, and weakness also have been reported with this condition.⁴ Cutaneous polyarteritis nodosa has been associated with abnormal antibody testing with elevations of antiphospholipid cofactor antibody, lupus anticoagulant, anticardiolipin antibody, and anti-β₂-glycoprotein I–dependent cardiolipin antibody, as well as elevated anti–phosphatidylserine-prothrombin complex antibody.⁵ These antibodies suggest increased risk for thrombosis and systemic diseases such as lupus or other autoimmune connective tissue disease. The distinction of this entity from systemic polyartertitis nodosa is key when determining treatment options and monitoring parameters.

Case Report

A 66-year-old woman was referred to our facility by an outside dermatologist with a mildly pruritic, blanchable, reticulated erythema on the chest and bilateral arms and legs of 3 months’ duration consistent with livedo reticularis (Figure 1). Prior systemic therapy included prednisone 10 mg 3 times daily, fexofenadine, loratadine, and hydroxyzine. When the systemic steroid was tapered, the patient developed an asymptomatic flare of her eruption. On presentation, the lesions had waxed and waned, and the patient was taking only vitamin B₁₂ and vitamin C. Her medical history was notable for an unknown-type lymphoma of the chest wall diagnosed at 46 years of age that was treated with an unknown chemotherapeutic agent, chronic pancreatitis that resulted in a duodenectomy at 61 years of age, chronic cholecystitis, and 1 first-trimester miscarriage. Outside laboratory tests, including a comprehensive metabolic panel, complete blood cell count, urinalysis, renal function, and liver function tests were within reference range, except for the finding of mild leukocytosis (11,000/µL)(reference range, 3800–10,800/µL), which resolved after steroids were discontinued, with otherwise normal results. Punch biopsy of a specimen from the right thigh revealed medium-vessel vasculitis consistent with polyarteritis nodosa (Figure 2). Laboratory workup by our facility including hepatitis panel, perinuclear antineutrophil cytoplasmic antibody, cytoplasmic antineutrophil cytoplasmic antibody, factor V Leiden, prothrombin time/international normalized ratio, anticardiolipin antibody, and proteins C and S were all within reference range. Abnormal values included a low positive but nondiagnostic antinuclear antibody screen with negative titers, and the lupus anticoagulant titer was mildly elevated at 44 IgG binding units (reference range, <40 IgG binding units). Serum protein electrophoresis (SPEP) and urine protein electrophoresis also were performed, and SPEP was low positive for elevated κ and γ light chains. The patient was referred to oncology, and further testing revealed no underlying malignancy. The patient was monitored and no treatment was initiated; her rash completely resolved within 3 months. Laboratory monitoring at 6 months including SPEP, urine protein electrophoresis, lupus anticoagulant, and clotting studies all were within reference range.

Comment

Although the treatment of systemic polyarteritis nodosa often is necessary and typically involves high-dose corticosteroids and cyclophosphamide, the treatment of CPAN initially is less aggressive. Of the options available for treatment of CPAN, each has associated risks and side effects. Chen⁶ classified CPAN into 3 groups: 1 (mild), 2 (severe with no systemic involvement), and 3 (severe with progression to systemic disease)(Table). The authors performed a review of all the published treatments and their respective side effects to evaluate if treatment should be instituted for asymptomatic (group 1) disease presenting with abnormal antibody findings as demonstrated in our case.

First-line treatment of CPAN includes nonsteroidal anti-inflammatory drugs (NSAIDS) and colchicine.⁷ Nonsteroidal anti-inflammatory drugs are preferred; however, they also have been associated with gastrointestinal tract upset and increased risk for peptic ulcer disease with long-term use. Although colchicine often is used in conjunction with NSAIDS⁸ for its anti-inflammatory activity, no studies have been performed on this drug as monotherapy, and the side effect of diarrhea often limits its use.

Other therapies include dapsone, which should be monitored carefully due to the risk for dapsone hypersensitivity syndrome.^8,9 Topical corticosteroids have been proven effective for mild cases of confluent erythema with remission occurring as early as 4 weeks.⁴ Some reports emphasize the role of streptococcal infections in CPAN, especially in children.^8,10-12 Consequently it is recommended that anti–streptolysin O titers should be included in the workup for CPAN. Long-term penicillin prophylaxis and tonsillectomy have been used to prevent disease flares with limited success.^8,10-12

For more severe disease, especially with neuromuscular involvement, oral methylprednisolone up to 1 mg/kg daily has been used and has proven effective in the control of acute exacerbations.^7,13 However, the many adverse effects of systemic steroids limit their use long-term, and taper will often result in flare of disease.^4,7 Medications used in conjunction with steroids include hydroxychloroquine, dapsone, azathioprine, cyclophosphamide, methotrexate, sulfapyridine, pentoxifylline, infliximab, etanercept, and intravenous immunoglobulin.^4,9,12-17

Low-dose methotrexate has shown some improvement in skin disease with CPAN, but other case reports suggest that complete remission is not achieved with this drug.^15,18 More studies are needed to assess the use of methotrexate for CPAN.

Immunomodulators have been used in multiple case reports with varying levels of success. Rogalski and Sticherling⁴ reported 3 cases that cleared with methylprednisolone plus azathioprine ranging from 4 weeks to 6 months; nausea limited tolerance of azathioprine in 1 case. Mycophenolate mofetil also was successfully used in 2 cases with clearance at 17 weeks and 6 months. In this series of cases, cyclosporine was ineffective for CPAN.⁴ Two case reports documented cutaneous clearance with cyclophosphamide in conjunction with prednisolone.^9,10 No prospective trials have been performed on these medications, and immunosuppressants should only be considered in steroid-resistant cases.

The use of intravenous immunoglobulin has been reported effective in prior cases that showed resistance to more conventional trials of steroids, azathioprine, and/or cyclophosphamide.^12,14 Intravenous immunoglobulin may be regarded as a treatment option for severe resistant disease. Several case reports also have documented success using tumor necrosis factor α blockers, particularly infliximab, as an adjunct to steroids and etanercept as both a steroid adjunct and monotherapy.^16,17,19 More studies are necessary to evaluate these treatments.

Additionally, single case reports have outlined the use of other therapeutic agents, including tamoxifen (10 mg twice daily increased to 20 mg twice daily during episodes of breakthrough lesions),²⁰ hyperbaric oxygen therapy (100% oxygen for 90 minutes 5 times weekly at 1.5 atm absolute followed by 2 weeks of 2 atm absolute),²¹ and granulocyte-macrophage colony-stimulating factor (300 µg injection in small portion to ulcer edges twice monthly for 2 months).²² All of these treatments show promise, but data are limited.

Because thrombosis is postulated to be a potential mechanism leading to CPAN, agents such as pentoxifylline, clopidogrel, and warfarin have been examined as treatment options. Pentoxifylline in combination with mycophenolate mofetil has been successful in treating a case that was resistant to other immunosuppressants.²³ Clopidogrel blocks the adenosine diphosphate pathway and impairs clot retraction. Clopidogrel was reported effective in an acute flare of CPAN for clearance of skin lesions and normalization of lupus anticoagulant.²⁴ It also was used successfully in recurrent CPAN after steroid treatments in a patient with neuromuscular symptoms. There was no recurrence in either of the patients in this case report series. Warfarin therapy at an international normalized ratio of 3.0 also has demonstrated success in halting disease progression and in facilitating the resolution of skin changes and normalization of anti–phosphatidylserine-prothrombin complex antibodies.²⁴ Our review of the literature did not reveal evidence of a standardized length of treatment following symptom resolution or if treatment is indicated in asymptomatic disease, or as in our case, with only mild elevations of antiphospholipid antibodies.

Conclusion

Multiple treatment options exist for CPAN, but the data on their efficacies is limited and based only on anecdotal evidence, not prospective analysis. We believe that it seems reasonable to initiate treatment only for symptomatic disease or cases in which the antibody titers suggest that the patient may be at high risk for thrombosis. Mild symptoms and mild cutaneous changes would suggest the likely choice of NSAIDs, colchicine, or dapsone as treatment options versus no treatment. In patients with antibody titers, pentoxifylline, clopidogrel, or warfarin may be considered first-line therapies. With severe ulcerative lesions and neuromuscular involvement, steroids, immunosuppressants, and other investigative agents should be contemplated. In our patient, the laboratory studies were repeated and normalized on complete resolution of her livedo eruption. She remained asymptomatic and clear for 8 months without any treatment. The incidence of this presentation of CPAN is unknown and is likely underreported, as we would not expect most patients to present to their physicians for the evaluation of otherwise asymptomatic livedo reticularis. In essence, our case report suggests that it may be prudent to simply monitor patients with asymptomatic CPAN.

In 1931, Lindberg¹ described a cutaneous variant of polyarteritis nodosa, which lacked visceral involvement and possessed a more favorable prognosis.² Cutaneous polyarteritis nodosa (CPAN) is a localized small- to medium-vessel vasculitis restricted to the skin. Both benign and chronic courses have been described, and systemic involvement does not occur.³ Diagnostic criteria proposed by Nakamura et al³ in 2009 included cutaneous nodules, livedo reticularis, purpura, or ulcers; histopathologic fibrinoid necrotizing vasculitis of small- to medium-sized vessels; and exclusion of systemic symptoms (eg, fever, hypertension, weight loss, renal failure, cerebral hemorrhage, neuropathy, myocardial infarction, ischemic heart disease, pericarditis, pleuritis, arthralgia/myalgia). Nodules occur in 30% to 50% of cases and can remain for years if left untreated. Ulcerations occur in up to 30% of patients. Myositis, arthritis, and weakness also have been reported with this condition.⁴ Cutaneous polyarteritis nodosa has been associated with abnormal antibody testing with elevations of antiphospholipid cofactor antibody, lupus anticoagulant, anticardiolipin antibody, and anti-β₂-glycoprotein I–dependent cardiolipin antibody, as well as elevated anti–phosphatidylserine-prothrombin complex antibody.⁵ These antibodies suggest increased risk for thrombosis and systemic diseases such as lupus or other autoimmune connective tissue disease. The distinction of this entity from systemic polyartertitis nodosa is key when determining treatment options and monitoring parameters.

Case Report

A 66-year-old woman was referred to our facility by an outside dermatologist with a mildly pruritic, blanchable, reticulated erythema on the chest and bilateral arms and legs of 3 months’ duration consistent with livedo reticularis (Figure 1). Prior systemic therapy included prednisone 10 mg 3 times daily, fexofenadine, loratadine, and hydroxyzine. When the systemic steroid was tapered, the patient developed an asymptomatic flare of her eruption. On presentation, the lesions had waxed and waned, and the patient was taking only vitamin B₁₂ and vitamin C. Her medical history was notable for an unknown-type lymphoma of the chest wall diagnosed at 46 years of age that was treated with an unknown chemotherapeutic agent, chronic pancreatitis that resulted in a duodenectomy at 61 years of age, chronic cholecystitis, and 1 first-trimester miscarriage. Outside laboratory tests, including a comprehensive metabolic panel, complete blood cell count, urinalysis, renal function, and liver function tests were within reference range, except for the finding of mild leukocytosis (11,000/µL)(reference range, 3800–10,800/µL), which resolved after steroids were discontinued, with otherwise normal results. Punch biopsy of a specimen from the right thigh revealed medium-vessel vasculitis consistent with polyarteritis nodosa (Figure 2). Laboratory workup by our facility including hepatitis panel, perinuclear antineutrophil cytoplasmic antibody, cytoplasmic antineutrophil cytoplasmic antibody, factor V Leiden, prothrombin time/international normalized ratio, anticardiolipin antibody, and proteins C and S were all within reference range. Abnormal values included a low positive but nondiagnostic antinuclear antibody screen with negative titers, and the lupus anticoagulant titer was mildly elevated at 44 IgG binding units (reference range, <40 IgG binding units). Serum protein electrophoresis (SPEP) and urine protein electrophoresis also were performed, and SPEP was low positive for elevated κ and γ light chains. The patient was referred to oncology, and further testing revealed no underlying malignancy. The patient was monitored and no treatment was initiated; her rash completely resolved within 3 months. Laboratory monitoring at 6 months including SPEP, urine protein electrophoresis, lupus anticoagulant, and clotting studies all were within reference range.

Comment

Although the treatment of systemic polyarteritis nodosa often is necessary and typically involves high-dose corticosteroids and cyclophosphamide, the treatment of CPAN initially is less aggressive. Of the options available for treatment of CPAN, each has associated risks and side effects. Chen⁶ classified CPAN into 3 groups: 1 (mild), 2 (severe with no systemic involvement), and 3 (severe with progression to systemic disease)(Table). The authors performed a review of all the published treatments and their respective side effects to evaluate if treatment should be instituted for asymptomatic (group 1) disease presenting with abnormal antibody findings as demonstrated in our case.

First-line treatment of CPAN includes nonsteroidal anti-inflammatory drugs (NSAIDS) and colchicine.⁷ Nonsteroidal anti-inflammatory drugs are preferred; however, they also have been associated with gastrointestinal tract upset and increased risk for peptic ulcer disease with long-term use. Although colchicine often is used in conjunction with NSAIDS⁸ for its anti-inflammatory activity, no studies have been performed on this drug as monotherapy, and the side effect of diarrhea often limits its use.

Other therapies include dapsone, which should be monitored carefully due to the risk for dapsone hypersensitivity syndrome.^8,9 Topical corticosteroids have been proven effective for mild cases of confluent erythema with remission occurring as early as 4 weeks.⁴ Some reports emphasize the role of streptococcal infections in CPAN, especially in children.^8,10-12 Consequently it is recommended that anti–streptolysin O titers should be included in the workup for CPAN. Long-term penicillin prophylaxis and tonsillectomy have been used to prevent disease flares with limited success.^8,10-12

For more severe disease, especially with neuromuscular involvement, oral methylprednisolone up to 1 mg/kg daily has been used and has proven effective in the control of acute exacerbations.^7,13 However, the many adverse effects of systemic steroids limit their use long-term, and taper will often result in flare of disease.^4,7 Medications used in conjunction with steroids include hydroxychloroquine, dapsone, azathioprine, cyclophosphamide, methotrexate, sulfapyridine, pentoxifylline, infliximab, etanercept, and intravenous immunoglobulin.^4,9,12-17

Low-dose methotrexate has shown some improvement in skin disease with CPAN, but other case reports suggest that complete remission is not achieved with this drug.^15,18 More studies are needed to assess the use of methotrexate for CPAN.

Immunomodulators have been used in multiple case reports with varying levels of success. Rogalski and Sticherling⁴ reported 3 cases that cleared with methylprednisolone plus azathioprine ranging from 4 weeks to 6 months; nausea limited tolerance of azathioprine in 1 case. Mycophenolate mofetil also was successfully used in 2 cases with clearance at 17 weeks and 6 months. In this series of cases, cyclosporine was ineffective for CPAN.⁴ Two case reports documented cutaneous clearance with cyclophosphamide in conjunction with prednisolone.^9,10 No prospective trials have been performed on these medications, and immunosuppressants should only be considered in steroid-resistant cases.

The use of intravenous immunoglobulin has been reported effective in prior cases that showed resistance to more conventional trials of steroids, azathioprine, and/or cyclophosphamide.^12,14 Intravenous immunoglobulin may be regarded as a treatment option for severe resistant disease. Several case reports also have documented success using tumor necrosis factor α blockers, particularly infliximab, as an adjunct to steroids and etanercept as both a steroid adjunct and monotherapy.^16,17,19 More studies are necessary to evaluate these treatments.

Additionally, single case reports have outlined the use of other therapeutic agents, including tamoxifen (10 mg twice daily increased to 20 mg twice daily during episodes of breakthrough lesions),²⁰ hyperbaric oxygen therapy (100% oxygen for 90 minutes 5 times weekly at 1.5 atm absolute followed by 2 weeks of 2 atm absolute),²¹ and granulocyte-macrophage colony-stimulating factor (300 µg injection in small portion to ulcer edges twice monthly for 2 months).²² All of these treatments show promise, but data are limited.

Because thrombosis is postulated to be a potential mechanism leading to CPAN, agents such as pentoxifylline, clopidogrel, and warfarin have been examined as treatment options. Pentoxifylline in combination with mycophenolate mofetil has been successful in treating a case that was resistant to other immunosuppressants.²³ Clopidogrel blocks the adenosine diphosphate pathway and impairs clot retraction. Clopidogrel was reported effective in an acute flare of CPAN for clearance of skin lesions and normalization of lupus anticoagulant.²⁴ It also was used successfully in recurrent CPAN after steroid treatments in a patient with neuromuscular symptoms. There was no recurrence in either of the patients in this case report series. Warfarin therapy at an international normalized ratio of 3.0 also has demonstrated success in halting disease progression and in facilitating the resolution of skin changes and normalization of anti–phosphatidylserine-prothrombin complex antibodies.²⁴ Our review of the literature did not reveal evidence of a standardized length of treatment following symptom resolution or if treatment is indicated in asymptomatic disease, or as in our case, with only mild elevations of antiphospholipid antibodies.

Conclusion

Multiple treatment options exist for CPAN, but the data on their efficacies is limited and based only on anecdotal evidence, not prospective analysis. We believe that it seems reasonable to initiate treatment only for symptomatic disease or cases in which the antibody titers suggest that the patient may be at high risk for thrombosis. Mild symptoms and mild cutaneous changes would suggest the likely choice of NSAIDs, colchicine, or dapsone as treatment options versus no treatment. In patients with antibody titers, pentoxifylline, clopidogrel, or warfarin may be considered first-line therapies. With severe ulcerative lesions and neuromuscular involvement, steroids, immunosuppressants, and other investigative agents should be contemplated. In our patient, the laboratory studies were repeated and normalized on complete resolution of her livedo eruption. She remained asymptomatic and clear for 8 months without any treatment. The incidence of this presentation of CPAN is unknown and is likely underreported, as we would not expect most patients to present to their physicians for the evaluation of otherwise asymptomatic livedo reticularis. In essence, our case report suggests that it may be prudent to simply monitor patients with asymptomatic CPAN.

In 1931, Lindberg¹ described a cutaneous variant of polyarteritis nodosa, which lacked visceral involvement and possessed a more favorable prognosis.² Cutaneous polyarteritis nodosa (CPAN) is a localized small- to medium-vessel vasculitis restricted to the skin. Both benign and chronic courses have been described, and systemic involvement does not occur.³ Diagnostic criteria proposed by Nakamura et al³ in 2009 included cutaneous nodules, livedo reticularis, purpura, or ulcers; histopathologic fibrinoid necrotizing vasculitis of small- to medium-sized vessels; and exclusion of systemic symptoms (eg, fever, hypertension, weight loss, renal failure, cerebral hemorrhage, neuropathy, myocardial infarction, ischemic heart disease, pericarditis, pleuritis, arthralgia/myalgia). Nodules occur in 30% to 50% of cases and can remain for years if left untreated. Ulcerations occur in up to 30% of patients. Myositis, arthritis, and weakness also have been reported with this condition.⁴ Cutaneous polyarteritis nodosa has been associated with abnormal antibody testing with elevations of antiphospholipid cofactor antibody, lupus anticoagulant, anticardiolipin antibody, and anti-β₂-glycoprotein I–dependent cardiolipin antibody, as well as elevated anti–phosphatidylserine-prothrombin complex antibody.⁵ These antibodies suggest increased risk for thrombosis and systemic diseases such as lupus or other autoimmune connective tissue disease. The distinction of this entity from systemic polyartertitis nodosa is key when determining treatment options and monitoring parameters.

Case Report

A 66-year-old woman was referred to our facility by an outside dermatologist with a mildly pruritic, blanchable, reticulated erythema on the chest and bilateral arms and legs of 3 months’ duration consistent with livedo reticularis (Figure 1). Prior systemic therapy included prednisone 10 mg 3 times daily, fexofenadine, loratadine, and hydroxyzine. When the systemic steroid was tapered, the patient developed an asymptomatic flare of her eruption. On presentation, the lesions had waxed and waned, and the patient was taking only vitamin B₁₂ and vitamin C. Her medical history was notable for an unknown-type lymphoma of the chest wall diagnosed at 46 years of age that was treated with an unknown chemotherapeutic agent, chronic pancreatitis that resulted in a duodenectomy at 61 years of age, chronic cholecystitis, and 1 first-trimester miscarriage. Outside laboratory tests, including a comprehensive metabolic panel, complete blood cell count, urinalysis, renal function, and liver function tests were within reference range, except for the finding of mild leukocytosis (11,000/µL)(reference range, 3800–10,800/µL), which resolved after steroids were discontinued, with otherwise normal results. Punch biopsy of a specimen from the right thigh revealed medium-vessel vasculitis consistent with polyarteritis nodosa (Figure 2). Laboratory workup by our facility including hepatitis panel, perinuclear antineutrophil cytoplasmic antibody, cytoplasmic antineutrophil cytoplasmic antibody, factor V Leiden, prothrombin time/international normalized ratio, anticardiolipin antibody, and proteins C and S were all within reference range. Abnormal values included a low positive but nondiagnostic antinuclear antibody screen with negative titers, and the lupus anticoagulant titer was mildly elevated at 44 IgG binding units (reference range, <40 IgG binding units). Serum protein electrophoresis (SPEP) and urine protein electrophoresis also were performed, and SPEP was low positive for elevated κ and γ light chains. The patient was referred to oncology, and further testing revealed no underlying malignancy. The patient was monitored and no treatment was initiated; her rash completely resolved within 3 months. Laboratory monitoring at 6 months including SPEP, urine protein electrophoresis, lupus anticoagulant, and clotting studies all were within reference range.

Comment

Although the treatment of systemic polyarteritis nodosa often is necessary and typically involves high-dose corticosteroids and cyclophosphamide, the treatment of CPAN initially is less aggressive. Of the options available for treatment of CPAN, each has associated risks and side effects. Chen⁶ classified CPAN into 3 groups: 1 (mild), 2 (severe with no systemic involvement), and 3 (severe with progression to systemic disease)(Table). The authors performed a review of all the published treatments and their respective side effects to evaluate if treatment should be instituted for asymptomatic (group 1) disease presenting with abnormal antibody findings as demonstrated in our case.

First-line treatment of CPAN includes nonsteroidal anti-inflammatory drugs (NSAIDS) and colchicine.⁷ Nonsteroidal anti-inflammatory drugs are preferred; however, they also have been associated with gastrointestinal tract upset and increased risk for peptic ulcer disease with long-term use. Although colchicine often is used in conjunction with NSAIDS⁸ for its anti-inflammatory activity, no studies have been performed on this drug as monotherapy, and the side effect of diarrhea often limits its use.

Other therapies include dapsone, which should be monitored carefully due to the risk for dapsone hypersensitivity syndrome.^8,9 Topical corticosteroids have been proven effective for mild cases of confluent erythema with remission occurring as early as 4 weeks.⁴ Some reports emphasize the role of streptococcal infections in CPAN, especially in children.^8,10-12 Consequently it is recommended that anti–streptolysin O titers should be included in the workup for CPAN. Long-term penicillin prophylaxis and tonsillectomy have been used to prevent disease flares with limited success.^8,10-12

For more severe disease, especially with neuromuscular involvement, oral methylprednisolone up to 1 mg/kg daily has been used and has proven effective in the control of acute exacerbations.^7,13 However, the many adverse effects of systemic steroids limit their use long-term, and taper will often result in flare of disease.^4,7 Medications used in conjunction with steroids include hydroxychloroquine, dapsone, azathioprine, cyclophosphamide, methotrexate, sulfapyridine, pentoxifylline, infliximab, etanercept, and intravenous immunoglobulin.^4,9,12-17

Low-dose methotrexate has shown some improvement in skin disease with CPAN, but other case reports suggest that complete remission is not achieved with this drug.^15,18 More studies are needed to assess the use of methotrexate for CPAN.

Immunomodulators have been used in multiple case reports with varying levels of success. Rogalski and Sticherling⁴ reported 3 cases that cleared with methylprednisolone plus azathioprine ranging from 4 weeks to 6 months; nausea limited tolerance of azathioprine in 1 case. Mycophenolate mofetil also was successfully used in 2 cases with clearance at 17 weeks and 6 months. In this series of cases, cyclosporine was ineffective for CPAN.⁴ Two case reports documented cutaneous clearance with cyclophosphamide in conjunction with prednisolone.^9,10 No prospective trials have been performed on these medications, and immunosuppressants should only be considered in steroid-resistant cases.

The use of intravenous immunoglobulin has been reported effective in prior cases that showed resistance to more conventional trials of steroids, azathioprine, and/or cyclophosphamide.^12,14 Intravenous immunoglobulin may be regarded as a treatment option for severe resistant disease. Several case reports also have documented success using tumor necrosis factor α blockers, particularly infliximab, as an adjunct to steroids and etanercept as both a steroid adjunct and monotherapy.^16,17,19 More studies are necessary to evaluate these treatments.

Additionally, single case reports have outlined the use of other therapeutic agents, including tamoxifen (10 mg twice daily increased to 20 mg twice daily during episodes of breakthrough lesions),²⁰ hyperbaric oxygen therapy (100% oxygen for 90 minutes 5 times weekly at 1.5 atm absolute followed by 2 weeks of 2 atm absolute),²¹ and granulocyte-macrophage colony-stimulating factor (300 µg injection in small portion to ulcer edges twice monthly for 2 months).²² All of these treatments show promise, but data are limited.

Because thrombosis is postulated to be a potential mechanism leading to CPAN, agents such as pentoxifylline, clopidogrel, and warfarin have been examined as treatment options. Pentoxifylline in combination with mycophenolate mofetil has been successful in treating a case that was resistant to other immunosuppressants.²³ Clopidogrel blocks the adenosine diphosphate pathway and impairs clot retraction. Clopidogrel was reported effective in an acute flare of CPAN for clearance of skin lesions and normalization of lupus anticoagulant.²⁴ It also was used successfully in recurrent CPAN after steroid treatments in a patient with neuromuscular symptoms. There was no recurrence in either of the patients in this case report series. Warfarin therapy at an international normalized ratio of 3.0 also has demonstrated success in halting disease progression and in facilitating the resolution of skin changes and normalization of anti–phosphatidylserine-prothrombin complex antibodies.²⁴ Our review of the literature did not reveal evidence of a standardized length of treatment following symptom resolution or if treatment is indicated in asymptomatic disease, or as in our case, with only mild elevations of antiphospholipid antibodies.

Conclusion

Multiple treatment options exist for CPAN, but the data on their efficacies is limited and based only on anecdotal evidence, not prospective analysis. We believe that it seems reasonable to initiate treatment only for symptomatic disease or cases in which the antibody titers suggest that the patient may be at high risk for thrombosis. Mild symptoms and mild cutaneous changes would suggest the likely choice of NSAIDs, colchicine, or dapsone as treatment options versus no treatment. In patients with antibody titers, pentoxifylline, clopidogrel, or warfarin may be considered first-line therapies. With severe ulcerative lesions and neuromuscular involvement, steroids, immunosuppressants, and other investigative agents should be contemplated. In our patient, the laboratory studies were repeated and normalized on complete resolution of her livedo eruption. She remained asymptomatic and clear for 8 months without any treatment. The incidence of this presentation of CPAN is unknown and is likely underreported, as we would not expect most patients to present to their physicians for the evaluation of otherwise asymptomatic livedo reticularis. In essence, our case report suggests that it may be prudent to simply monitor patients with asymptomatic CPAN.