- Email: [email protected]
Association between Alopecia Areata, Psoriasis Vulgaris, Thyroid Disease, and Metabolic Syndrome
CASE REPORT
Association between Alopecia Areata, Psoriasis Vulgaris, Thyroid Disease, and Metabolic Syndrome Rim S. Ishak1 and Melissa P. Piliang1,2 Although the association between alopecia areata (AA), psoriasis, and other autoimmune diseases has been well reported in the literature, an association with metabolic syndrome has not been reported. We present two young women with the combination of severe psoriasis, androgen excess, metabolic syndrome, thyroiditis, and AA. Both women ultimately progressed to treatment-resistant alopecia universalis. This constellation of autoimmunity and metabolic syndrome presents a therapeutic challenge while highlighting the need for full laboratory assessment of AA patients. Careful selection of biological treatment regimens may offer therapeutic benefit for both their psoriasis and AA while giving us experience with the newer biologics in AA. Journal of Investigative Dermatology Symposium Proceedings (2013) 16, S56–S57; doi:10.1038/jidsymp.2013.22
PRESENTATION: PATIENT 1 Patient 1 is an 18-year-old woman with a history of psoriasis involving her scalp and body and psoriatic arthritis since the age of 5 years and patchy alopecia since the age of 15 years. HISTORY Her past medical history was remarkable for hypothyroidism, polycystic ovarian syndrome, obesity, and elevated lipid levels. She reported irregular periods and dark terminal hair on her upper lip and chin. Family history was remarkable for psoriasis, alopecia areata (AA), Hashimoto’s thyroiditis, and rheumatoid arthritis. Stressful triggers included the death of her father 6 years before and high anxiety related to school socialization. EXAMINATION Physical examination revealed an obese adolescent with a body mass index of 33.9 kg m 2. Her psoriasis involved 5% of her body surface area in the form of erythematous scaly plaques over bilateral shins. On her scalp were several smooth alopecic patches. She had nail pitting. INVESTIGATIONS Labs were unremarkable, except for a positive anti-nuclear antibody and an elevated free testosterone (11.7, normal range 1–9).
MANAGEMENT She received intralesional triamcinolone acetonide (5 mg ml 1, 4 ml per session) and initially she had full regrowth. About 1 year later, she suddenly developed new patches of AA. This was concomitant with extreme anxiety about the start of her school year, a 25-pound intentional weight loss, initiating adalimumab treatment, and recently diagnosed hypothyroidism. Notably, her psoriasis and psoriatic arthritis were under excellent control. OUTCOME The hair loss progressed to alopecia universalis within a few weeks. She was started on diphenylcyclopropenone with no improvement. PRESENTATION: PATIENT 2 Patient 2 is a 29-year-old woman with a 6-year history of pustular psoriasis and psoriatic arthritis treated with methotrexate, etanercept, and efalizumab. HISTORY Her medical history was also remarkable for obesity (body mass index 30.4 kg m 2), Hashimoto’s thyroiditis, polymorphic eruption of pregnancy, and atopic dermatitis. Five years after the diagnosis of psoriasis, she developed an abrupt onset of scalp and body hair loss eventually progressing to alopecia universalis. Stress triggers included work and family difficulties (mother of four children), birth of a child, and an extremely restrictive high protein, low carbohydrate diet. She had lost a total of 25 pounds in the 6 weeks before the hair shedding. Her periods were irregular. She had a strong family history of metabolic syndrome (cardiovascular disease, obesity, diabetes, hyperlipidemia), psoriasis, thyroid abnormalities, and atopic dermatitis. EXAMINATION On physical examination, she had diffuse thinning of her scalp hair, with background patchy alopecia, thinning of lateral eyebrows (Figure 1), and diffuse alopecia of her arms and legs. Her fingernails were pitted, and her big toenails were onycholytic. Her psoriasis was mainly confined to the soles, with well demarcated slightly erythematous plaques and overlying thick white scales.
1
Department of Dermatology, Cleveland Clinic, Cleveland, Ohio, USA and 2Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio, USA
Correspondence: Melissa P. Piliang, Department of Dermatology, Cleveland Clinic, 9500 Euclid Avenue, A61, Cleveland, Ohio 44195, USA. E-mail: [email protected]
S56
Journal of Investigative Dermatology Symposium Proceedings (2013), Volume 16
& 2013 The Society for Investigative Dermatology
RS Ishak and MP Piliang Association Between Alopecia Areata and Other Diseases
Figure 1. Alopecic patches involving the frontal hairline and scattered throughout the scalp with loss of lateral eyebrow.
INVESTIGATIONS Laboratory investigations were all normal, except for slightly elevated free testosterone (2.1%, normal range 0.3–1.9%). MANAGEMENT AND OUTCOME Her alopecia was treated with diphenylcyclopropenone, biotin, and iron, but after several months she failed all treatments and opted not to seek any further therapy. DISCUSSION The constellation of autoimmune disorders in our two patients is interesting, and many factors come into consideration. There is compelling evidence that patients with psoriasis and psoriatic arthritis have a higher risk to develop other autoimmune disorders, particularly AA, with two large population studies demonstrating an odds ratio of 2.4 (Chu et al., 2011; Wu et al., 2012). Both our patients had strong family histories of autoimmunity, thus illustrating their elevated risk, and both suffered from thyroid abnormalities, which could contribute to their hair loss. It is interesting that in these patients, their AA flared as their psoriasis control improved after initiating therapy with biological agents. Ferran et al. (2011) reports that this is often associated with a poorer prognosis. Contrary to the initial hope that tumor necrosis factor a (TNFa) may have a role in the pathogenesis of AA, many reports have demonstrated the inefficiency of anti-TNFa drugs in the treatment of AA (Strober et al., 2005).
The complex cytokine milieu continues to be elucidated in both psoriasis and AA. It is important to keep in mind, as it signifies how psoriasis (T helper type 17 (Th17) cytokines) can inhibit some inflammatory processes, such as those seen in AA (Th1). Our patients are illustrative of the phenomenon of worsening AA after successful treatment of their psoriasis. The Renbok phenomenon describes patients with AA and psoriasis who regrow hair within their psoriatic plaques, which further illustrates the complex immunological overlap between AA and psoriasis. The immunological interplay between psoriasis and AA must be considered when selecting therapeutic regimens for these complex patients, in order to avoid worsening one of their inflammatory conditions while treating the other. Although the association between the metabolic syndrome and psoriasis and other autoimmune inflammatory diseases has been extensively studied, this association has not been studied in AA. Both of our patients fulfill the criteria for metabolic abnormalities associated with their chronic inflammatory conditions. This further emphasize that dermatologists should screen such patients for autoimmune disorders associated with psoriasis and AA, in addition to full metabolic panel workups to avoid missing any underlying abnormalities. Further studies to investigate an association between AA and increased risk of cardiovascular and metabolic diseases is warranted. CONFLICT OF INTEREST The authors state no conflict of interest.
ACKNOWLEDGMENTS Funding for the Summit and publication of this article was provided by the National Alopecia Areata Foundation. Informed consent for publication provided by the patient.
REFERENCES Chu SY, Chen YJ, Tseng WC et al. (2011) Comorbidity profiles among patients with alopecia areata: the importance of onset age, a nationwide population-based study. J Am Acad Dermatol 65:949–56 Ferran M, Calvet J, Almirall M et al. (2011) Alopecia areata as another immune-mediated disease developed in patients treated with tumour necrosis factor-a blocker agents: report of five cases and review of the literature. J Eur Acad Dermatol Venereol 25:479–84 Strober BE, Siu K, Alexis AF et al. (2005) Etanercept does not effectively treat moderate to severe alopecia areata: an open-label study. J Am Acad Dermatol 52:159–63 Wu JJ, Nguyen TU, Poon KY et al. (2012) The association of psoriasis with autoimmune diseases. J Am Acad Dermatol 67:924–30
www.jidonline.org
S57
Association between Alopecia Areata, Psoriasis Vulgaris, Thyroid Disease, and Metabolic Syndrome Rim S. Ishak1 and Melissa P. Piliang1,2 Although the association between alopecia areata (AA), psoriasis, and other autoimmune diseases has been well reported in the literature, an association with metabolic syndrome has not been reported. We present two young women with the combination of severe psoriasis, androgen excess, metabolic syndrome, thyroiditis, and AA. Both women ultimately progressed to treatment-resistant alopecia universalis. This constellation of autoimmunity and metabolic syndrome presents a therapeutic challenge while highlighting the need for full laboratory assessment of AA patients. Careful selection of biological treatment regimens may offer therapeutic benefit for both their psoriasis and AA while giving us experience with the newer biologics in AA. Journal of Investigative Dermatology Symposium Proceedings (2013) 16, S56–S57; doi:10.1038/jidsymp.2013.22
PRESENTATION: PATIENT 1 Patient 1 is an 18-year-old woman with a history of psoriasis involving her scalp and body and psoriatic arthritis since the age of 5 years and patchy alopecia since the age of 15 years. HISTORY Her past medical history was remarkable for hypothyroidism, polycystic ovarian syndrome, obesity, and elevated lipid levels. She reported irregular periods and dark terminal hair on her upper lip and chin. Family history was remarkable for psoriasis, alopecia areata (AA), Hashimoto’s thyroiditis, and rheumatoid arthritis. Stressful triggers included the death of her father 6 years before and high anxiety related to school socialization. EXAMINATION Physical examination revealed an obese adolescent with a body mass index of 33.9 kg m 2. Her psoriasis involved 5% of her body surface area in the form of erythematous scaly plaques over bilateral shins. On her scalp were several smooth alopecic patches. She had nail pitting. INVESTIGATIONS Labs were unremarkable, except for a positive anti-nuclear antibody and an elevated free testosterone (11.7, normal range 1–9).
MANAGEMENT She received intralesional triamcinolone acetonide (5 mg ml 1, 4 ml per session) and initially she had full regrowth. About 1 year later, she suddenly developed new patches of AA. This was concomitant with extreme anxiety about the start of her school year, a 25-pound intentional weight loss, initiating adalimumab treatment, and recently diagnosed hypothyroidism. Notably, her psoriasis and psoriatic arthritis were under excellent control. OUTCOME The hair loss progressed to alopecia universalis within a few weeks. She was started on diphenylcyclopropenone with no improvement. PRESENTATION: PATIENT 2 Patient 2 is a 29-year-old woman with a 6-year history of pustular psoriasis and psoriatic arthritis treated with methotrexate, etanercept, and efalizumab. HISTORY Her medical history was also remarkable for obesity (body mass index 30.4 kg m 2), Hashimoto’s thyroiditis, polymorphic eruption of pregnancy, and atopic dermatitis. Five years after the diagnosis of psoriasis, she developed an abrupt onset of scalp and body hair loss eventually progressing to alopecia universalis. Stress triggers included work and family difficulties (mother of four children), birth of a child, and an extremely restrictive high protein, low carbohydrate diet. She had lost a total of 25 pounds in the 6 weeks before the hair shedding. Her periods were irregular. She had a strong family history of metabolic syndrome (cardiovascular disease, obesity, diabetes, hyperlipidemia), psoriasis, thyroid abnormalities, and atopic dermatitis. EXAMINATION On physical examination, she had diffuse thinning of her scalp hair, with background patchy alopecia, thinning of lateral eyebrows (Figure 1), and diffuse alopecia of her arms and legs. Her fingernails were pitted, and her big toenails were onycholytic. Her psoriasis was mainly confined to the soles, with well demarcated slightly erythematous plaques and overlying thick white scales.
1
Department of Dermatology, Cleveland Clinic, Cleveland, Ohio, USA and 2Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio, USA
Correspondence: Melissa P. Piliang, Department of Dermatology, Cleveland Clinic, 9500 Euclid Avenue, A61, Cleveland, Ohio 44195, USA. E-mail: [email protected]
S56
Journal of Investigative Dermatology Symposium Proceedings (2013), Volume 16
& 2013 The Society for Investigative Dermatology
RS Ishak and MP Piliang Association Between Alopecia Areata and Other Diseases
Figure 1. Alopecic patches involving the frontal hairline and scattered throughout the scalp with loss of lateral eyebrow.
INVESTIGATIONS Laboratory investigations were all normal, except for slightly elevated free testosterone (2.1%, normal range 0.3–1.9%). MANAGEMENT AND OUTCOME Her alopecia was treated with diphenylcyclopropenone, biotin, and iron, but after several months she failed all treatments and opted not to seek any further therapy. DISCUSSION The constellation of autoimmune disorders in our two patients is interesting, and many factors come into consideration. There is compelling evidence that patients with psoriasis and psoriatic arthritis have a higher risk to develop other autoimmune disorders, particularly AA, with two large population studies demonstrating an odds ratio of 2.4 (Chu et al., 2011; Wu et al., 2012). Both our patients had strong family histories of autoimmunity, thus illustrating their elevated risk, and both suffered from thyroid abnormalities, which could contribute to their hair loss. It is interesting that in these patients, their AA flared as their psoriasis control improved after initiating therapy with biological agents. Ferran et al. (2011) reports that this is often associated with a poorer prognosis. Contrary to the initial hope that tumor necrosis factor a (TNFa) may have a role in the pathogenesis of AA, many reports have demonstrated the inefficiency of anti-TNFa drugs in the treatment of AA (Strober et al., 2005).
The complex cytokine milieu continues to be elucidated in both psoriasis and AA. It is important to keep in mind, as it signifies how psoriasis (T helper type 17 (Th17) cytokines) can inhibit some inflammatory processes, such as those seen in AA (Th1). Our patients are illustrative of the phenomenon of worsening AA after successful treatment of their psoriasis. The Renbok phenomenon describes patients with AA and psoriasis who regrow hair within their psoriatic plaques, which further illustrates the complex immunological overlap between AA and psoriasis. The immunological interplay between psoriasis and AA must be considered when selecting therapeutic regimens for these complex patients, in order to avoid worsening one of their inflammatory conditions while treating the other. Although the association between the metabolic syndrome and psoriasis and other autoimmune inflammatory diseases has been extensively studied, this association has not been studied in AA. Both of our patients fulfill the criteria for metabolic abnormalities associated with their chronic inflammatory conditions. This further emphasize that dermatologists should screen such patients for autoimmune disorders associated with psoriasis and AA, in addition to full metabolic panel workups to avoid missing any underlying abnormalities. Further studies to investigate an association between AA and increased risk of cardiovascular and metabolic diseases is warranted. CONFLICT OF INTEREST The authors state no conflict of interest.
ACKNOWLEDGMENTS Funding for the Summit and publication of this article was provided by the National Alopecia Areata Foundation. Informed consent for publication provided by the patient.
REFERENCES Chu SY, Chen YJ, Tseng WC et al. (2011) Comorbidity profiles among patients with alopecia areata: the importance of onset age, a nationwide population-based study. J Am Acad Dermatol 65:949–56 Ferran M, Calvet J, Almirall M et al. (2011) Alopecia areata as another immune-mediated disease developed in patients treated with tumour necrosis factor-a blocker agents: report of five cases and review of the literature. J Eur Acad Dermatol Venereol 25:479–84 Strober BE, Siu K, Alexis AF et al. (2005) Etanercept does not effectively treat moderate to severe alopecia areata: an open-label study. J Am Acad Dermatol 52:159–63 Wu JJ, Nguyen TU, Poon KY et al. (2012) The association of psoriasis with autoimmune diseases. J Am Acad Dermatol 67:924–30
www.jidonline.org
S57