Carolyn Goh, MD

Anagen effluvium during chemotherapy is common, typically beginning within 1 month of treatment onset and resolving by 6 months after the final course.¹ Permanent chemotherapy-induced alopecia (PCIA), in which hair loss persists beyond 6 months after chemotherapy without recovery to original density, was first reported in patients following high-dose chemotherapy regimens for allogeneic bone marrow transplantation.² There are now increasing reports of PCIA in patients with breast cancer; at least 400 such cases have been documented.^3-16 In addition to chemotherapy, patients often receive adjuvant endocrine therapy with selective estrogen receptor modulators, aromatase inhibitors, or gonadotropin-releasing hormone agonists.^5-16 Endocrine therapies also can lead to alopecia, but their role in PCIA has not been well defined.^15,16 We describe 3 patients with breast cancer who experienced PCIA following chemotherapy with taxanes with or without endocrine therapies. We also review the literature on non–bone marrow transplantation PCIA to better characterize this entity and explore the role of endocrine therapies in PCIA.

Case Reports

Patient 1
A 62-year-old woman with a history of stage II invasive ductal carcinoma presented with persistent hair loss 5 years after completing chemotherapy. She underwent 6 cycles of docetaxel and carboplatin along with radiation therapy as well as 1 year of trastuzumab and did not receive endocrine therapy. At the current presentation, she reported patchy hair regrowth that gradually filled in but failed to return to full density. Physical examination revealed the hair was diffusely thin, especially bitemporally (Figures 1A and 1B), and she did not experience any loss of body hair. She had no family history of hair loss. Her medical history was notable for hypertension, chronic obstructive bronchitis, osteopenia, and depression. Her thyroid stimulating hormone (TSH) level was within reference range. Medications included lisinopril, metoprolol, escitalopram, and trazodone. A biopsy from the occipital scalp showed nonscarring alopecia with variation of hair follicle size, a decreased number of hair follicles, and a decreased anagen to telogen ratio (Figure 1C). She was treated with clobetasol solution and minoxidil solution 5% for 1 year with mild improvement. She experienced no further hair loss but did not regain original hair density.

Patient 2
A 35-year-old woman with a history of stage II invasive ductal carcinoma presented with persistent hair loss 10 months after chemotherapy. She underwent 4 cycles of doxorubicin and cyclophosphamide followed by 4 cycles of paclitaxel and was started on trastuzumab. Tamoxifen was initiated 1 month after completing chemotherapy. She received radiation therapy the following month and continued trastuzumab for 1 year. At the current presentation, the patient noted that hair regrowth had started 1 month after the last course of chemotherapy but had progressed slowly. She denied body hair loss. Physical examination revealed diffuse thinning, especially over the crown, with scattered broken hairs throughout the scalp and several miniaturized hairs over the crown. She was evaluated as grade 3 on the Sinclair clinical grading scale used to evaluate female pattern hair loss (FPHL).¹⁷ Her family history was remarkable for FPHL in her maternal grandmother. She had no notable medical history, her TSH was normal, and she was taking tamoxifen and trastuzumab. Biopsy was not performed. The patient was started on minoxidil solution 2% and had mild improvement with no further broken-off hairs after 10 months. At that point, she was evaluated as grade 2 to 3 on the Sinclair scale.¹⁷

Patient 3
A 51-year-old woman with a history of papillary carcinoma and extensive ductal carcinoma in situ presented with persistent hair loss for 3.5 years following chemotherapy for recurrent breast cancer. After her initial diagnosis in the left breast, she received cyclophosphamide, methotrexate, and 5-fluorouracil but did not receive endocrine therapy. Her hair thinned during chemotherapy but returned to normal density within 1 year. She had a recurrence of the cancer in the right breast 14 years later and received 6 cycles of chemotherapy with cyclophosphamide and docetaxel followed by radiation therapy. After this course, her hair loss incompletely recovered. One year after chemotherapy, she underwent bilateral salpingo-oophorectomy and started anastrozole. Three months later, she noticed increased shedding and progressive thinning of the hair. Physical examination revealed diffuse thinning that was most pronounced over the crown. She also experienced lateral thinning of the eyebrows, decreased eyelashes, and dystrophic fingernails. Fluocinonide solution was discontinued by the patient due to scalp burning. She had a brother with bitemporal recession. Her medical history was notable for Hashimoto thyroiditis, vitamin D deficiency, and peripheral neuropathy. Her TSH occasionally was elevated, and she was intermittently on levothyroxine; however, her free T4 was maintained within reference range on all records. Her medications at the time of evaluation were anastrozole and gabapentin. Biopsies taken from the right and left temporal scalp revealed decreased follicle density with a majority of follicles in anagen, scattered miniaturized follicles, and a mild perivascular and perifollicular lymphoid infiltrate. Mild dermal fibrosis was present without evidence of frank scarring (Figure 2). She declined treatment, and there was no change in her condition over 3 years of follow-up.

Comment

Classification of Chemotherapy-Induced Hair Loss
Chemotherapy-induced alopecia is typically an anagen effluvium that is reversed within 6 months following the final course of chemotherapy. When incomplete regrowth persists, the patient is considered to have PCIA.¹ The pathophysiology of PCIA is unclear.

Traditional grading for chemotherapy-induced alopecia does not account for the patterns of loss seen in PCIA, of which the most common appears to be a female pattern with accentuated hair loss in androgen-dependent regions of the scalp.¹⁸ Other patterns include a diffuse type with body hair loss, patchy alopecia, and complete alopecia with or without body hair loss (Table).^3-8 Whether these patterns all can be attributed to chemotherapy remains to be explored.

Furthermore, endocrine therapies used in breast cancer treatment decrease estrogen levels or antagonize estrogen receptors, creating an environment of relative hyperandrogenism that may contribute to FPHL in genetically susceptible women.¹⁸ Although taxanes may cause irreversible hair loss in these patients, the action of endocrine therapies on the remaining hair follicles may affect the typical female pattern seen clinically. Patients 2 and 3 who presented with FPHL received adjuvant endocrine therapies and had positive family history, while patient 1 did not. Of note, patient 3 experienced worsening hair loss following the addition of anastrozole, which suggests a contribution of endocrine therapy to her PCIA. Our limited cases do not allow for evaluation of a worsened outcome with the combination of taxanes and endocrine therapies; however, we suggest further evaluation for a synergistic effect that may be contributing to PCIA.

Conclusion

Permanent alopecia in breast cancer patients appears to be a true potential adverse effect of taxanes and endocrine therapies, and it is important to characterize it appropriately so that its mechanism can be understood and appropriate treatment and counseling can take place. Although it may not influence clinical decision-making, patients should be informed that hair loss with chemotherapy can be permanent. Treatment with scalp cooling can reduce the risk for severe chemotherapy-induced alopecia, but it is unclear if it reduces risk for PCIA.^12,15 Topical or oral minoxidil may be helpful in the treatment of PCIA once it has developed.^7,8,15,22 Better characterization of these cases may elucidate risk factors for developing permanent alopecia, allowing for more appropriate risk stratification, counseling, and treatment.

Anagen effluvium during chemotherapy is common, typically beginning within 1 month of treatment onset and resolving by 6 months after the final course.¹ Permanent chemotherapy-induced alopecia (PCIA), in which hair loss persists beyond 6 months after chemotherapy without recovery to original density, was first reported in patients following high-dose chemotherapy regimens for allogeneic bone marrow transplantation.² There are now increasing reports of PCIA in patients with breast cancer; at least 400 such cases have been documented.^3-16 In addition to chemotherapy, patients often receive adjuvant endocrine therapy with selective estrogen receptor modulators, aromatase inhibitors, or gonadotropin-releasing hormone agonists.^5-16 Endocrine therapies also can lead to alopecia, but their role in PCIA has not been well defined.^15,16 We describe 3 patients with breast cancer who experienced PCIA following chemotherapy with taxanes with or without endocrine therapies. We also review the literature on non–bone marrow transplantation PCIA to better characterize this entity and explore the role of endocrine therapies in PCIA.

Case Reports

Patient 1
A 62-year-old woman with a history of stage II invasive ductal carcinoma presented with persistent hair loss 5 years after completing chemotherapy. She underwent 6 cycles of docetaxel and carboplatin along with radiation therapy as well as 1 year of trastuzumab and did not receive endocrine therapy. At the current presentation, she reported patchy hair regrowth that gradually filled in but failed to return to full density. Physical examination revealed the hair was diffusely thin, especially bitemporally (Figures 1A and 1B), and she did not experience any loss of body hair. She had no family history of hair loss. Her medical history was notable for hypertension, chronic obstructive bronchitis, osteopenia, and depression. Her thyroid stimulating hormone (TSH) level was within reference range. Medications included lisinopril, metoprolol, escitalopram, and trazodone. A biopsy from the occipital scalp showed nonscarring alopecia with variation of hair follicle size, a decreased number of hair follicles, and a decreased anagen to telogen ratio (Figure 1C). She was treated with clobetasol solution and minoxidil solution 5% for 1 year with mild improvement. She experienced no further hair loss but did not regain original hair density.

Patient 2
A 35-year-old woman with a history of stage II invasive ductal carcinoma presented with persistent hair loss 10 months after chemotherapy. She underwent 4 cycles of doxorubicin and cyclophosphamide followed by 4 cycles of paclitaxel and was started on trastuzumab. Tamoxifen was initiated 1 month after completing chemotherapy. She received radiation therapy the following month and continued trastuzumab for 1 year. At the current presentation, the patient noted that hair regrowth had started 1 month after the last course of chemotherapy but had progressed slowly. She denied body hair loss. Physical examination revealed diffuse thinning, especially over the crown, with scattered broken hairs throughout the scalp and several miniaturized hairs over the crown. She was evaluated as grade 3 on the Sinclair clinical grading scale used to evaluate female pattern hair loss (FPHL).¹⁷ Her family history was remarkable for FPHL in her maternal grandmother. She had no notable medical history, her TSH was normal, and she was taking tamoxifen and trastuzumab. Biopsy was not performed. The patient was started on minoxidil solution 2% and had mild improvement with no further broken-off hairs after 10 months. At that point, she was evaluated as grade 2 to 3 on the Sinclair scale.¹⁷

Patient 3
A 51-year-old woman with a history of papillary carcinoma and extensive ductal carcinoma in situ presented with persistent hair loss for 3.5 years following chemotherapy for recurrent breast cancer. After her initial diagnosis in the left breast, she received cyclophosphamide, methotrexate, and 5-fluorouracil but did not receive endocrine therapy. Her hair thinned during chemotherapy but returned to normal density within 1 year. She had a recurrence of the cancer in the right breast 14 years later and received 6 cycles of chemotherapy with cyclophosphamide and docetaxel followed by radiation therapy. After this course, her hair loss incompletely recovered. One year after chemotherapy, she underwent bilateral salpingo-oophorectomy and started anastrozole. Three months later, she noticed increased shedding and progressive thinning of the hair. Physical examination revealed diffuse thinning that was most pronounced over the crown. She also experienced lateral thinning of the eyebrows, decreased eyelashes, and dystrophic fingernails. Fluocinonide solution was discontinued by the patient due to scalp burning. She had a brother with bitemporal recession. Her medical history was notable for Hashimoto thyroiditis, vitamin D deficiency, and peripheral neuropathy. Her TSH occasionally was elevated, and she was intermittently on levothyroxine; however, her free T4 was maintained within reference range on all records. Her medications at the time of evaluation were anastrozole and gabapentin. Biopsies taken from the right and left temporal scalp revealed decreased follicle density with a majority of follicles in anagen, scattered miniaturized follicles, and a mild perivascular and perifollicular lymphoid infiltrate. Mild dermal fibrosis was present without evidence of frank scarring (Figure 2). She declined treatment, and there was no change in her condition over 3 years of follow-up.

Comment

Classification of Chemotherapy-Induced Hair Loss
Chemotherapy-induced alopecia is typically an anagen effluvium that is reversed within 6 months following the final course of chemotherapy. When incomplete regrowth persists, the patient is considered to have PCIA.¹ The pathophysiology of PCIA is unclear.

Traditional grading for chemotherapy-induced alopecia does not account for the patterns of loss seen in PCIA, of which the most common appears to be a female pattern with accentuated hair loss in androgen-dependent regions of the scalp.¹⁸ Other patterns include a diffuse type with body hair loss, patchy alopecia, and complete alopecia with or without body hair loss (Table).^3-8 Whether these patterns all can be attributed to chemotherapy remains to be explored.

Furthermore, endocrine therapies used in breast cancer treatment decrease estrogen levels or antagonize estrogen receptors, creating an environment of relative hyperandrogenism that may contribute to FPHL in genetically susceptible women.¹⁸ Although taxanes may cause irreversible hair loss in these patients, the action of endocrine therapies on the remaining hair follicles may affect the typical female pattern seen clinically. Patients 2 and 3 who presented with FPHL received adjuvant endocrine therapies and had positive family history, while patient 1 did not. Of note, patient 3 experienced worsening hair loss following the addition of anastrozole, which suggests a contribution of endocrine therapy to her PCIA. Our limited cases do not allow for evaluation of a worsened outcome with the combination of taxanes and endocrine therapies; however, we suggest further evaluation for a synergistic effect that may be contributing to PCIA.

Conclusion

Permanent alopecia in breast cancer patients appears to be a true potential adverse effect of taxanes and endocrine therapies, and it is important to characterize it appropriately so that its mechanism can be understood and appropriate treatment and counseling can take place. Although it may not influence clinical decision-making, patients should be informed that hair loss with chemotherapy can be permanent. Treatment with scalp cooling can reduce the risk for severe chemotherapy-induced alopecia, but it is unclear if it reduces risk for PCIA.^12,15 Topical or oral minoxidil may be helpful in the treatment of PCIA once it has developed.^7,8,15,22 Better characterization of these cases may elucidate risk factors for developing permanent alopecia, allowing for more appropriate risk stratification, counseling, and treatment.

Anagen effluvium during chemotherapy is common, typically beginning within 1 month of treatment onset and resolving by 6 months after the final course.¹ Permanent chemotherapy-induced alopecia (PCIA), in which hair loss persists beyond 6 months after chemotherapy without recovery to original density, was first reported in patients following high-dose chemotherapy regimens for allogeneic bone marrow transplantation.² There are now increasing reports of PCIA in patients with breast cancer; at least 400 such cases have been documented.^3-16 In addition to chemotherapy, patients often receive adjuvant endocrine therapy with selective estrogen receptor modulators, aromatase inhibitors, or gonadotropin-releasing hormone agonists.^5-16 Endocrine therapies also can lead to alopecia, but their role in PCIA has not been well defined.^15,16 We describe 3 patients with breast cancer who experienced PCIA following chemotherapy with taxanes with or without endocrine therapies. We also review the literature on non–bone marrow transplantation PCIA to better characterize this entity and explore the role of endocrine therapies in PCIA.

Case Reports

Patient 1
A 62-year-old woman with a history of stage II invasive ductal carcinoma presented with persistent hair loss 5 years after completing chemotherapy. She underwent 6 cycles of docetaxel and carboplatin along with radiation therapy as well as 1 year of trastuzumab and did not receive endocrine therapy. At the current presentation, she reported patchy hair regrowth that gradually filled in but failed to return to full density. Physical examination revealed the hair was diffusely thin, especially bitemporally (Figures 1A and 1B), and she did not experience any loss of body hair. She had no family history of hair loss. Her medical history was notable for hypertension, chronic obstructive bronchitis, osteopenia, and depression. Her thyroid stimulating hormone (TSH) level was within reference range. Medications included lisinopril, metoprolol, escitalopram, and trazodone. A biopsy from the occipital scalp showed nonscarring alopecia with variation of hair follicle size, a decreased number of hair follicles, and a decreased anagen to telogen ratio (Figure 1C). She was treated with clobetasol solution and minoxidil solution 5% for 1 year with mild improvement. She experienced no further hair loss but did not regain original hair density.

Patient 2
A 35-year-old woman with a history of stage II invasive ductal carcinoma presented with persistent hair loss 10 months after chemotherapy. She underwent 4 cycles of doxorubicin and cyclophosphamide followed by 4 cycles of paclitaxel and was started on trastuzumab. Tamoxifen was initiated 1 month after completing chemotherapy. She received radiation therapy the following month and continued trastuzumab for 1 year. At the current presentation, the patient noted that hair regrowth had started 1 month after the last course of chemotherapy but had progressed slowly. She denied body hair loss. Physical examination revealed diffuse thinning, especially over the crown, with scattered broken hairs throughout the scalp and several miniaturized hairs over the crown. She was evaluated as grade 3 on the Sinclair clinical grading scale used to evaluate female pattern hair loss (FPHL).¹⁷ Her family history was remarkable for FPHL in her maternal grandmother. She had no notable medical history, her TSH was normal, and she was taking tamoxifen and trastuzumab. Biopsy was not performed. The patient was started on minoxidil solution 2% and had mild improvement with no further broken-off hairs after 10 months. At that point, she was evaluated as grade 2 to 3 on the Sinclair scale.¹⁷

Patient 3
A 51-year-old woman with a history of papillary carcinoma and extensive ductal carcinoma in situ presented with persistent hair loss for 3.5 years following chemotherapy for recurrent breast cancer. After her initial diagnosis in the left breast, she received cyclophosphamide, methotrexate, and 5-fluorouracil but did not receive endocrine therapy. Her hair thinned during chemotherapy but returned to normal density within 1 year. She had a recurrence of the cancer in the right breast 14 years later and received 6 cycles of chemotherapy with cyclophosphamide and docetaxel followed by radiation therapy. After this course, her hair loss incompletely recovered. One year after chemotherapy, she underwent bilateral salpingo-oophorectomy and started anastrozole. Three months later, she noticed increased shedding and progressive thinning of the hair. Physical examination revealed diffuse thinning that was most pronounced over the crown. She also experienced lateral thinning of the eyebrows, decreased eyelashes, and dystrophic fingernails. Fluocinonide solution was discontinued by the patient due to scalp burning. She had a brother with bitemporal recession. Her medical history was notable for Hashimoto thyroiditis, vitamin D deficiency, and peripheral neuropathy. Her TSH occasionally was elevated, and she was intermittently on levothyroxine; however, her free T4 was maintained within reference range on all records. Her medications at the time of evaluation were anastrozole and gabapentin. Biopsies taken from the right and left temporal scalp revealed decreased follicle density with a majority of follicles in anagen, scattered miniaturized follicles, and a mild perivascular and perifollicular lymphoid infiltrate. Mild dermal fibrosis was present without evidence of frank scarring (Figure 2). She declined treatment, and there was no change in her condition over 3 years of follow-up.

Comment

Classification of Chemotherapy-Induced Hair Loss
Chemotherapy-induced alopecia is typically an anagen effluvium that is reversed within 6 months following the final course of chemotherapy. When incomplete regrowth persists, the patient is considered to have PCIA.¹ The pathophysiology of PCIA is unclear.

Traditional grading for chemotherapy-induced alopecia does not account for the patterns of loss seen in PCIA, of which the most common appears to be a female pattern with accentuated hair loss in androgen-dependent regions of the scalp.¹⁸ Other patterns include a diffuse type with body hair loss, patchy alopecia, and complete alopecia with or without body hair loss (Table).^3-8 Whether these patterns all can be attributed to chemotherapy remains to be explored.

Furthermore, endocrine therapies used in breast cancer treatment decrease estrogen levels or antagonize estrogen receptors, creating an environment of relative hyperandrogenism that may contribute to FPHL in genetically susceptible women.¹⁸ Although taxanes may cause irreversible hair loss in these patients, the action of endocrine therapies on the remaining hair follicles may affect the typical female pattern seen clinically. Patients 2 and 3 who presented with FPHL received adjuvant endocrine therapies and had positive family history, while patient 1 did not. Of note, patient 3 experienced worsening hair loss following the addition of anastrozole, which suggests a contribution of endocrine therapy to her PCIA. Our limited cases do not allow for evaluation of a worsened outcome with the combination of taxanes and endocrine therapies; however, we suggest further evaluation for a synergistic effect that may be contributing to PCIA.

Conclusion

Permanent alopecia in breast cancer patients appears to be a true potential adverse effect of taxanes and endocrine therapies, and it is important to characterize it appropriately so that its mechanism can be understood and appropriate treatment and counseling can take place. Although it may not influence clinical decision-making, patients should be informed that hair loss with chemotherapy can be permanent. Treatment with scalp cooling can reduce the risk for severe chemotherapy-induced alopecia, but it is unclear if it reduces risk for PCIA.^12,15 Topical or oral minoxidil may be helpful in the treatment of PCIA once it has developed.^7,8,15,22 Better characterization of these cases may elucidate risk factors for developing permanent alopecia, allowing for more appropriate risk stratification, counseling, and treatment.

To the Editor:

Lymphomatoid papulosis is a rare chronic skin disorder characterized by recurrent, self-healing crops of papulonodular eruptions, often resembling cutaneous T-cell lymphoma.¹ Oral bexarotene, a retinoid X receptor–selective retinoid, can be used to control the disease.^2,3 Lichen planopilaris (LPP) is a type of cicatricial alopecia characterized by irreversible hair loss, perifollicular inflammation, and follicular hyperkeratosis, commonly affecting the scalp vertex in adults.⁴ We report a case of a patient with lymphomatoid papulosis who was treated with bexarotene and subsequently developed LPP. We also discuss a proposed mechanism by which bexarotene may have influenced the onset of LPP.

A 35-year-old woman who was previously healthy initially presented with recurrent pruritic papular eruptions on the flank, axillae, and groin of several months’ duration. The lesions appeared as 2-mm, flat-topped, violaceous papules. The patient had no known drug allergies, no medical or family history of skin disease, and was only taking 3000 mg/d of omega-3 fatty acids (fish oil). Histopathologic examination of a biopsy specimen from the inner thigh showed enlarged, atypical, dermal lymphocytes that were CD30⁺ (Figure 1). These findings were consistent with lymphomatoid papulosis. As she had undergone tubal ligation several years prior, she was prescribed oral bexarotene 300 mg once daily in addition to triamcinolone cream 0.1% twice daily, as needed. Symptoms were well controlled on this regimen.

Although the exact mechanism of LPP is not fully understood, studies have suggested that cellular lipid metabolism may be responsible for the inflammation of the pilosebaceous unit.^4-11 Hyperlipidemia is the most common side effect of oral bexarotene, typically occurring within the first 2 to 4 weeks of treatment.^3,12 Considering the insights into the role of lipid regulation on LPP pathogenesis, it is reasonable to suspect that the dyslipidemia caused by bexarotene may have triggered the onset of LPP in our patient. The patient’s lipid values mostly remained within reference range throughout the course of treatment, though she did have elevation of triglycerides around the onset of LPP. Dyslipidemia has been reported in patients with lichen planus but not in patients with LPP. One case-control study showed no dyslipidemia in patients with LPP, but the triglyceride levels were not tracked over time and patients had varying durations since onset of disease at presentation.^9-11,13 In our case, we were fortunate to have this information, and it may suggest an interaction between lipid dysregulation and the development of LPP. It would be interesting to explore this further in a larger patient population and to evaluate if control of dyslipidemia reduces progression of disease as it appears to have done for our patient.

To the Editor:

Lymphomatoid papulosis is a rare chronic skin disorder characterized by recurrent, self-healing crops of papulonodular eruptions, often resembling cutaneous T-cell lymphoma.¹ Oral bexarotene, a retinoid X receptor–selective retinoid, can be used to control the disease.^2,3 Lichen planopilaris (LPP) is a type of cicatricial alopecia characterized by irreversible hair loss, perifollicular inflammation, and follicular hyperkeratosis, commonly affecting the scalp vertex in adults.⁴ We report a case of a patient with lymphomatoid papulosis who was treated with bexarotene and subsequently developed LPP. We also discuss a proposed mechanism by which bexarotene may have influenced the onset of LPP.

A 35-year-old woman who was previously healthy initially presented with recurrent pruritic papular eruptions on the flank, axillae, and groin of several months’ duration. The lesions appeared as 2-mm, flat-topped, violaceous papules. The patient had no known drug allergies, no medical or family history of skin disease, and was only taking 3000 mg/d of omega-3 fatty acids (fish oil). Histopathologic examination of a biopsy specimen from the inner thigh showed enlarged, atypical, dermal lymphocytes that were CD30⁺ (Figure 1). These findings were consistent with lymphomatoid papulosis. As she had undergone tubal ligation several years prior, she was prescribed oral bexarotene 300 mg once daily in addition to triamcinolone cream 0.1% twice daily, as needed. Symptoms were well controlled on this regimen.

Although the exact mechanism of LPP is not fully understood, studies have suggested that cellular lipid metabolism may be responsible for the inflammation of the pilosebaceous unit.^4-11 Hyperlipidemia is the most common side effect of oral bexarotene, typically occurring within the first 2 to 4 weeks of treatment.^3,12 Considering the insights into the role of lipid regulation on LPP pathogenesis, it is reasonable to suspect that the dyslipidemia caused by bexarotene may have triggered the onset of LPP in our patient. The patient’s lipid values mostly remained within reference range throughout the course of treatment, though she did have elevation of triglycerides around the onset of LPP. Dyslipidemia has been reported in patients with lichen planus but not in patients with LPP. One case-control study showed no dyslipidemia in patients with LPP, but the triglyceride levels were not tracked over time and patients had varying durations since onset of disease at presentation.^9-11,13 In our case, we were fortunate to have this information, and it may suggest an interaction between lipid dysregulation and the development of LPP. It would be interesting to explore this further in a larger patient population and to evaluate if control of dyslipidemia reduces progression of disease as it appears to have done for our patient.

To the Editor:

Lymphomatoid papulosis is a rare chronic skin disorder characterized by recurrent, self-healing crops of papulonodular eruptions, often resembling cutaneous T-cell lymphoma.¹ Oral bexarotene, a retinoid X receptor–selective retinoid, can be used to control the disease.^2,3 Lichen planopilaris (LPP) is a type of cicatricial alopecia characterized by irreversible hair loss, perifollicular inflammation, and follicular hyperkeratosis, commonly affecting the scalp vertex in adults.⁴ We report a case of a patient with lymphomatoid papulosis who was treated with bexarotene and subsequently developed LPP. We also discuss a proposed mechanism by which bexarotene may have influenced the onset of LPP.

A 35-year-old woman who was previously healthy initially presented with recurrent pruritic papular eruptions on the flank, axillae, and groin of several months’ duration. The lesions appeared as 2-mm, flat-topped, violaceous papules. The patient had no known drug allergies, no medical or family history of skin disease, and was only taking 3000 mg/d of omega-3 fatty acids (fish oil). Histopathologic examination of a biopsy specimen from the inner thigh showed enlarged, atypical, dermal lymphocytes that were CD30⁺ (Figure 1). These findings were consistent with lymphomatoid papulosis. As she had undergone tubal ligation several years prior, she was prescribed oral bexarotene 300 mg once daily in addition to triamcinolone cream 0.1% twice daily, as needed. Symptoms were well controlled on this regimen.

Although the exact mechanism of LPP is not fully understood, studies have suggested that cellular lipid metabolism may be responsible for the inflammation of the pilosebaceous unit.^4-11 Hyperlipidemia is the most common side effect of oral bexarotene, typically occurring within the first 2 to 4 weeks of treatment.^3,12 Considering the insights into the role of lipid regulation on LPP pathogenesis, it is reasonable to suspect that the dyslipidemia caused by bexarotene may have triggered the onset of LPP in our patient. The patient’s lipid values mostly remained within reference range throughout the course of treatment, though she did have elevation of triglycerides around the onset of LPP. Dyslipidemia has been reported in patients with lichen planus but not in patients with LPP. One case-control study showed no dyslipidemia in patients with LPP, but the triglyceride levels were not tracked over time and patients had varying durations since onset of disease at presentation.^9-11,13 In our case, we were fortunate to have this information, and it may suggest an interaction between lipid dysregulation and the development of LPP. It would be interesting to explore this further in a larger patient population and to evaluate if control of dyslipidemia reduces progression of disease as it appears to have done for our patient.

To the Editor:

Both alopecia areata (AA) and psoriasis vulgaris are chronic relapsing autoimmune diseases, with AA causing nonscarring hair loss in approximately 0.1% to 0.2%¹ of the population with a lifetime risk of 1.7%,² and psoriasis more broadly impacting 1.5% to 2% of the population.³ The helper T cell (T_H1) cytokine milieu is pathogenic in both conditions.^4-6 IFN-γ knockout mice, unlike their wild-type counterparts, do not exhibit AA.⁷ Psoriasis is notably improved by IL-10 injections, which dampen the T_H1 response.⁸ Distinct from AA, T_H17 and T_H22 cells have been implicated as key players in psoriasis pathogenesis, along with the associated IL-17 and IL-22 cytokines.^9-12

Few cases of patients with concurrent AA and psoriasis have been described. Interestingly, these cases document normal hair regrowth in the areas of psoriasis.^13-16 These cases may offer unique insight into the immune factors driving each disease. We describe a case of a man with both alopecia universalis (AU) and psoriasis who developed hair regrowth in some of the psoriatic plaques.

A 34-year-old man with concurrent AU and psoriasis who had not used any systemic or topical medication for either condition in the last year presented to our clinic seeking treatment. The patient had a history of alopecia totalis as a toddler that completely resolved by 4 years of age with the use of squaric acid dibutylester (SADBE). At 31 years of age, the alopecia recurred and was localized to the scalp. It was partially responsive to intralesional triamcinolone acetonide. The patient’s alopecia worsened over the 2 years following recurrence, ultimately progressing to AU. Two months after the alopecia recurrence, he developed the first psoriatic plaques. As the plaque psoriasis progressed, systemic therapy was initiated, first methotrexate and then etanercept. Shortly after developing AU, he lost his health insurance and discontinued all therapy. The patient’s psoriasis began to recur approximately 3 months after stopping etanercept. He was not using any other psoriasis medications. At that time, he noted terminal hair regrowth within some of the psoriatic plaques. No terminal hairs grew outside of the psoriatic plaques, and all regions with growth had previously been without hair for an extended period of time. The patient presented to our clinic approximately 1 year later. He had no other medical conditions and no relevant family history.

On initial physical examination, he had nonscarring hair loss involving nearly 100% of the body with psoriatic plaques on approximately 30% of the body surface area. Regions of terminal hair growth were confined to some but not all of the psoriatic plaques (Figure). Interestingly, the terminal hairs were primarily localized to the thickest central regions of the plaques. The patient’s psoriasis was treated with a combination of topical clobetasol and calcipotriene. In addition, he was started on tacrolimus ointment to the face and eyebrows for the AA. Maintenance of terminal hair within a region of topically treated psoriasis on the forearm persisted at the 2-month follow-up despite complete clearance of the corresponding psoriatic plaque. A small psoriatic plaque on the scalp cleared early with topical therapy without noticeable hair regrowth. The patient subsequently was started on contact immunotherapy with SADBE and intralesional triamcinolone acetonide for the scalp alopecia without satisfactory response. He decided to discontinue further attempts at treating the alopecia and requested to be restarted on etanercept therapy for recalcitrant psoriatic plaques. His psoriasis responded well to this therapy and he continues to be followed in our psoriasis clinic. One year after clearance of the treated psoriatic plaques, the corresponding terminal hairs persist.

Contact immunotherapy, most commonly with diphenylcyclopropenone or SADBE, is reported to have a 50% to 60% success rate in extensive AA, with a broad range of 9% to 87%¹⁷; however, randomized controlled trials testing the efficacy of contact immunotherapy are lacking. Although the mechanism of action of these topical sensitizers is not clearly delineated, it has been postulated that by inducing a new type of inflammatory response in the region, the immunologic milieu is changed, allowing the hair to grow. Some proposed mechanisms include promoting perifollicular lymphocyte apoptosis, preventing new recruitment of autoreactive lymphocytes, and allowing for the correction of aberrant major histocompatibility complex expression on the hair matrix epithelium to regain follicle immune privilege.^18-20

Iatrogenic immunotherapy may work analogously to the natural immune system deviation demonstrated in our patient. Psoriasis and AA are believed to form competing immune cells and cytokine milieus, thus explaining how an individual with AA could regain normal hair growth in areas of psoriasis.^15,16 The Renbök phenomenon, or reverse Köbner phenomenon, coined by Happle et al¹³ can be used to describe both the iatrogenic and natural cases of dermatologic disease improvement in response to secondary insults.¹⁴

A complex cascade of immune cells and cytokines coordinate AA pathogenesis. In the acute stage of AA, an inflammatory infiltrate of CD4⁺ T cells, CD8⁺ T cells, and antigen-presenting cells target anagen phase follicles, with a higher CD4⁺:CD8⁺ ratio in clinically active disease.^21-23 Subcutaneous injections of either CD4⁺ or CD8⁺ lymphocyte subsets from mice with AA into normal-haired mice induces disease. However, CD8⁺ T cell injections rapidly produce apparent hair loss, whereas CD4⁺ T cells cause hair loss after several weeks, suggesting that CD8⁺ T cells directly modulate AA hair loss and CD4⁺ T cells act as an aide.²⁴ The growth, differentiation, and survival of CD8⁺ T cells are stimulated by IL-2 and IFN-γ. Alopecia areata biopsies demonstrate a prevalence of T_H1 cytokines, and patients with localized AA, alopecia totalis, and AU have notably higher serum IFN-γ levels compared to controls.²⁵ In murine models, IL-1α and IL-1β increase during the catagen phase of the hair cycle and peak during the telogen phase.²⁶ Excessive IL-1β expression is detected in the early stages of human disease, and certain IL-1β polymorphisms are associated with severe forms of AA.²⁶ The role of tumor necrosis factor (TNF) α in AA is not well understood. In vitro studies show it inhibits hair growth, suggesting the cytokine may play a role in AA.²⁷ However, anti–TNF-α therapy is not effective in AA, and case reports propose these therapies rarely induce AA.^28-31

The T_H1 response is likewise critical to psoriatic plaque development. IFN-γ and TNF-α are overexpressed in psoriatic plaques.³² IFN-γ has an antiproliferative and differentiation-inducing effect on normal keratinocytes, but psoriatic epithelial cells in vitro respond differently to the cytokine with a notably diminished growth inhibition.^33,34 One explanation for the role of IFN-γ is that it stimulates dendritic cells to produce IL-1 and IL-23.³⁵ IL-23 activates T_H17 cells³⁶; T_H1 and T_H17 conditions produce IL-22 whose serum level correlates with disease severity.^37-39 IL-22 induces keratinocyte proliferation and migration and inhibits keratinocyte differentiation, helping account for hallmarks of the disease.⁴⁰ Patients with psoriasis have increased levels of T_H1, T_H17, and T_H22 cells, as well as their associated cytokines, in the skin and blood compared to controls.^{4,11,32,39,41}

Alopecia areata and psoriasis are regulated by complex and still not entirely understood immune interactions. The fact that many of the same therapies are used to treat both diseases emphasizes both their overlapping characteristics and the lack of targeted therapy. It is unclear if and how the topical or systemic therapies used in our patient to treat one disease affected the natural history of the other condition. It is important to highlight, however, that the patient had not been treated for months when he developed the psoriatic plaques with hair regrowth. Other case reports also document hair regrowth in untreated plaques,^13,16 making it unlikely to be a side effect of the medication regimen. For both psoriasis and AA, the immune cell composition and cytokine levels in the skin or serum vary throughout a patient’s disease course depending on severity of disease or response to treatment.^6,39,42,43 Therefore, we hypothesize that the 2 conditions interact in a similarly distinct manner based on each disease’s stage and intensity in the patient. Both our patient’s course thus far and the various presentations described by other groups support this hypothesis. Our patient had a small region of psoriasis on the scalp that cleared without any terminal hair growth. He also had larger plaques on the forearms that developed hair growth most predominantly within the thicker regions of the plaques. His unique presentation highlights the fluidity of the immune factors driving psoriasis vulgaris and AA.

To the Editor:

Both alopecia areata (AA) and psoriasis vulgaris are chronic relapsing autoimmune diseases, with AA causing nonscarring hair loss in approximately 0.1% to 0.2%¹ of the population with a lifetime risk of 1.7%,² and psoriasis more broadly impacting 1.5% to 2% of the population.³ The helper T cell (T_H1) cytokine milieu is pathogenic in both conditions.^4-6 IFN-γ knockout mice, unlike their wild-type counterparts, do not exhibit AA.⁷ Psoriasis is notably improved by IL-10 injections, which dampen the T_H1 response.⁸ Distinct from AA, T_H17 and T_H22 cells have been implicated as key players in psoriasis pathogenesis, along with the associated IL-17 and IL-22 cytokines.^9-12

Few cases of patients with concurrent AA and psoriasis have been described. Interestingly, these cases document normal hair regrowth in the areas of psoriasis.^13-16 These cases may offer unique insight into the immune factors driving each disease. We describe a case of a man with both alopecia universalis (AU) and psoriasis who developed hair regrowth in some of the psoriatic plaques.

A 34-year-old man with concurrent AU and psoriasis who had not used any systemic or topical medication for either condition in the last year presented to our clinic seeking treatment. The patient had a history of alopecia totalis as a toddler that completely resolved by 4 years of age with the use of squaric acid dibutylester (SADBE). At 31 years of age, the alopecia recurred and was localized to the scalp. It was partially responsive to intralesional triamcinolone acetonide. The patient’s alopecia worsened over the 2 years following recurrence, ultimately progressing to AU. Two months after the alopecia recurrence, he developed the first psoriatic plaques. As the plaque psoriasis progressed, systemic therapy was initiated, first methotrexate and then etanercept. Shortly after developing AU, he lost his health insurance and discontinued all therapy. The patient’s psoriasis began to recur approximately 3 months after stopping etanercept. He was not using any other psoriasis medications. At that time, he noted terminal hair regrowth within some of the psoriatic plaques. No terminal hairs grew outside of the psoriatic plaques, and all regions with growth had previously been without hair for an extended period of time. The patient presented to our clinic approximately 1 year later. He had no other medical conditions and no relevant family history.

On initial physical examination, he had nonscarring hair loss involving nearly 100% of the body with psoriatic plaques on approximately 30% of the body surface area. Regions of terminal hair growth were confined to some but not all of the psoriatic plaques (Figure). Interestingly, the terminal hairs were primarily localized to the thickest central regions of the plaques. The patient’s psoriasis was treated with a combination of topical clobetasol and calcipotriene. In addition, he was started on tacrolimus ointment to the face and eyebrows for the AA. Maintenance of terminal hair within a region of topically treated psoriasis on the forearm persisted at the 2-month follow-up despite complete clearance of the corresponding psoriatic plaque. A small psoriatic plaque on the scalp cleared early with topical therapy without noticeable hair regrowth. The patient subsequently was started on contact immunotherapy with SADBE and intralesional triamcinolone acetonide for the scalp alopecia without satisfactory response. He decided to discontinue further attempts at treating the alopecia and requested to be restarted on etanercept therapy for recalcitrant psoriatic plaques. His psoriasis responded well to this therapy and he continues to be followed in our psoriasis clinic. One year after clearance of the treated psoriatic plaques, the corresponding terminal hairs persist.

Contact immunotherapy, most commonly with diphenylcyclopropenone or SADBE, is reported to have a 50% to 60% success rate in extensive AA, with a broad range of 9% to 87%¹⁷; however, randomized controlled trials testing the efficacy of contact immunotherapy are lacking. Although the mechanism of action of these topical sensitizers is not clearly delineated, it has been postulated that by inducing a new type of inflammatory response in the region, the immunologic milieu is changed, allowing the hair to grow. Some proposed mechanisms include promoting perifollicular lymphocyte apoptosis, preventing new recruitment of autoreactive lymphocytes, and allowing for the correction of aberrant major histocompatibility complex expression on the hair matrix epithelium to regain follicle immune privilege.^18-20

Iatrogenic immunotherapy may work analogously to the natural immune system deviation demonstrated in our patient. Psoriasis and AA are believed to form competing immune cells and cytokine milieus, thus explaining how an individual with AA could regain normal hair growth in areas of psoriasis.^15,16 The Renbök phenomenon, or reverse Köbner phenomenon, coined by Happle et al¹³ can be used to describe both the iatrogenic and natural cases of dermatologic disease improvement in response to secondary insults.¹⁴

A complex cascade of immune cells and cytokines coordinate AA pathogenesis. In the acute stage of AA, an inflammatory infiltrate of CD4⁺ T cells, CD8⁺ T cells, and antigen-presenting cells target anagen phase follicles, with a higher CD4⁺:CD8⁺ ratio in clinically active disease.^21-23 Subcutaneous injections of either CD4⁺ or CD8⁺ lymphocyte subsets from mice with AA into normal-haired mice induces disease. However, CD8⁺ T cell injections rapidly produce apparent hair loss, whereas CD4⁺ T cells cause hair loss after several weeks, suggesting that CD8⁺ T cells directly modulate AA hair loss and CD4⁺ T cells act as an aide.²⁴ The growth, differentiation, and survival of CD8⁺ T cells are stimulated by IL-2 and IFN-γ. Alopecia areata biopsies demonstrate a prevalence of T_H1 cytokines, and patients with localized AA, alopecia totalis, and AU have notably higher serum IFN-γ levels compared to controls.²⁵ In murine models, IL-1α and IL-1β increase during the catagen phase of the hair cycle and peak during the telogen phase.²⁶ Excessive IL-1β expression is detected in the early stages of human disease, and certain IL-1β polymorphisms are associated with severe forms of AA.²⁶ The role of tumor necrosis factor (TNF) α in AA is not well understood. In vitro studies show it inhibits hair growth, suggesting the cytokine may play a role in AA.²⁷ However, anti–TNF-α therapy is not effective in AA, and case reports propose these therapies rarely induce AA.^28-31

The T_H1 response is likewise critical to psoriatic plaque development. IFN-γ and TNF-α are overexpressed in psoriatic plaques.³² IFN-γ has an antiproliferative and differentiation-inducing effect on normal keratinocytes, but psoriatic epithelial cells in vitro respond differently to the cytokine with a notably diminished growth inhibition.^33,34 One explanation for the role of IFN-γ is that it stimulates dendritic cells to produce IL-1 and IL-23.³⁵ IL-23 activates T_H17 cells³⁶; T_H1 and T_H17 conditions produce IL-22 whose serum level correlates with disease severity.^37-39 IL-22 induces keratinocyte proliferation and migration and inhibits keratinocyte differentiation, helping account for hallmarks of the disease.⁴⁰ Patients with psoriasis have increased levels of T_H1, T_H17, and T_H22 cells, as well as their associated cytokines, in the skin and blood compared to controls.^{4,11,32,39,41}

Alopecia areata and psoriasis are regulated by complex and still not entirely understood immune interactions. The fact that many of the same therapies are used to treat both diseases emphasizes both their overlapping characteristics and the lack of targeted therapy. It is unclear if and how the topical or systemic therapies used in our patient to treat one disease affected the natural history of the other condition. It is important to highlight, however, that the patient had not been treated for months when he developed the psoriatic plaques with hair regrowth. Other case reports also document hair regrowth in untreated plaques,^13,16 making it unlikely to be a side effect of the medication regimen. For both psoriasis and AA, the immune cell composition and cytokine levels in the skin or serum vary throughout a patient’s disease course depending on severity of disease or response to treatment.^6,39,42,43 Therefore, we hypothesize that the 2 conditions interact in a similarly distinct manner based on each disease’s stage and intensity in the patient. Both our patient’s course thus far and the various presentations described by other groups support this hypothesis. Our patient had a small region of psoriasis on the scalp that cleared without any terminal hair growth. He also had larger plaques on the forearms that developed hair growth most predominantly within the thicker regions of the plaques. His unique presentation highlights the fluidity of the immune factors driving psoriasis vulgaris and AA.

To the Editor:

Both alopecia areata (AA) and psoriasis vulgaris are chronic relapsing autoimmune diseases, with AA causing nonscarring hair loss in approximately 0.1% to 0.2%¹ of the population with a lifetime risk of 1.7%,² and psoriasis more broadly impacting 1.5% to 2% of the population.³ The helper T cell (T_H1) cytokine milieu is pathogenic in both conditions.^4-6 IFN-γ knockout mice, unlike their wild-type counterparts, do not exhibit AA.⁷ Psoriasis is notably improved by IL-10 injections, which dampen the T_H1 response.⁸ Distinct from AA, T_H17 and T_H22 cells have been implicated as key players in psoriasis pathogenesis, along with the associated IL-17 and IL-22 cytokines.^9-12

Few cases of patients with concurrent AA and psoriasis have been described. Interestingly, these cases document normal hair regrowth in the areas of psoriasis.^13-16 These cases may offer unique insight into the immune factors driving each disease. We describe a case of a man with both alopecia universalis (AU) and psoriasis who developed hair regrowth in some of the psoriatic plaques.

A 34-year-old man with concurrent AU and psoriasis who had not used any systemic or topical medication for either condition in the last year presented to our clinic seeking treatment. The patient had a history of alopecia totalis as a toddler that completely resolved by 4 years of age with the use of squaric acid dibutylester (SADBE). At 31 years of age, the alopecia recurred and was localized to the scalp. It was partially responsive to intralesional triamcinolone acetonide. The patient’s alopecia worsened over the 2 years following recurrence, ultimately progressing to AU. Two months after the alopecia recurrence, he developed the first psoriatic plaques. As the plaque psoriasis progressed, systemic therapy was initiated, first methotrexate and then etanercept. Shortly after developing AU, he lost his health insurance and discontinued all therapy. The patient’s psoriasis began to recur approximately 3 months after stopping etanercept. He was not using any other psoriasis medications. At that time, he noted terminal hair regrowth within some of the psoriatic plaques. No terminal hairs grew outside of the psoriatic plaques, and all regions with growth had previously been without hair for an extended period of time. The patient presented to our clinic approximately 1 year later. He had no other medical conditions and no relevant family history.

On initial physical examination, he had nonscarring hair loss involving nearly 100% of the body with psoriatic plaques on approximately 30% of the body surface area. Regions of terminal hair growth were confined to some but not all of the psoriatic plaques (Figure). Interestingly, the terminal hairs were primarily localized to the thickest central regions of the plaques. The patient’s psoriasis was treated with a combination of topical clobetasol and calcipotriene. In addition, he was started on tacrolimus ointment to the face and eyebrows for the AA. Maintenance of terminal hair within a region of topically treated psoriasis on the forearm persisted at the 2-month follow-up despite complete clearance of the corresponding psoriatic plaque. A small psoriatic plaque on the scalp cleared early with topical therapy without noticeable hair regrowth. The patient subsequently was started on contact immunotherapy with SADBE and intralesional triamcinolone acetonide for the scalp alopecia without satisfactory response. He decided to discontinue further attempts at treating the alopecia and requested to be restarted on etanercept therapy for recalcitrant psoriatic plaques. His psoriasis responded well to this therapy and he continues to be followed in our psoriasis clinic. One year after clearance of the treated psoriatic plaques, the corresponding terminal hairs persist.

Contact immunotherapy, most commonly with diphenylcyclopropenone or SADBE, is reported to have a 50% to 60% success rate in extensive AA, with a broad range of 9% to 87%¹⁷; however, randomized controlled trials testing the efficacy of contact immunotherapy are lacking. Although the mechanism of action of these topical sensitizers is not clearly delineated, it has been postulated that by inducing a new type of inflammatory response in the region, the immunologic milieu is changed, allowing the hair to grow. Some proposed mechanisms include promoting perifollicular lymphocyte apoptosis, preventing new recruitment of autoreactive lymphocytes, and allowing for the correction of aberrant major histocompatibility complex expression on the hair matrix epithelium to regain follicle immune privilege.^18-20

Iatrogenic immunotherapy may work analogously to the natural immune system deviation demonstrated in our patient. Psoriasis and AA are believed to form competing immune cells and cytokine milieus, thus explaining how an individual with AA could regain normal hair growth in areas of psoriasis.^15,16 The Renbök phenomenon, or reverse Köbner phenomenon, coined by Happle et al¹³ can be used to describe both the iatrogenic and natural cases of dermatologic disease improvement in response to secondary insults.¹⁴

A complex cascade of immune cells and cytokines coordinate AA pathogenesis. In the acute stage of AA, an inflammatory infiltrate of CD4⁺ T cells, CD8⁺ T cells, and antigen-presenting cells target anagen phase follicles, with a higher CD4⁺:CD8⁺ ratio in clinically active disease.^21-23 Subcutaneous injections of either CD4⁺ or CD8⁺ lymphocyte subsets from mice with AA into normal-haired mice induces disease. However, CD8⁺ T cell injections rapidly produce apparent hair loss, whereas CD4⁺ T cells cause hair loss after several weeks, suggesting that CD8⁺ T cells directly modulate AA hair loss and CD4⁺ T cells act as an aide.²⁴ The growth, differentiation, and survival of CD8⁺ T cells are stimulated by IL-2 and IFN-γ. Alopecia areata biopsies demonstrate a prevalence of T_H1 cytokines, and patients with localized AA, alopecia totalis, and AU have notably higher serum IFN-γ levels compared to controls.²⁵ In murine models, IL-1α and IL-1β increase during the catagen phase of the hair cycle and peak during the telogen phase.²⁶ Excessive IL-1β expression is detected in the early stages of human disease, and certain IL-1β polymorphisms are associated with severe forms of AA.²⁶ The role of tumor necrosis factor (TNF) α in AA is not well understood. In vitro studies show it inhibits hair growth, suggesting the cytokine may play a role in AA.²⁷ However, anti–TNF-α therapy is not effective in AA, and case reports propose these therapies rarely induce AA.^28-31

The T_H1 response is likewise critical to psoriatic plaque development. IFN-γ and TNF-α are overexpressed in psoriatic plaques.³² IFN-γ has an antiproliferative and differentiation-inducing effect on normal keratinocytes, but psoriatic epithelial cells in vitro respond differently to the cytokine with a notably diminished growth inhibition.^33,34 One explanation for the role of IFN-γ is that it stimulates dendritic cells to produce IL-1 and IL-23.³⁵ IL-23 activates T_H17 cells³⁶; T_H1 and T_H17 conditions produce IL-22 whose serum level correlates with disease severity.^37-39 IL-22 induces keratinocyte proliferation and migration and inhibits keratinocyte differentiation, helping account for hallmarks of the disease.⁴⁰ Patients with psoriasis have increased levels of T_H1, T_H17, and T_H22 cells, as well as their associated cytokines, in the skin and blood compared to controls.^{4,11,32,39,41}

Alopecia areata and psoriasis are regulated by complex and still not entirely understood immune interactions. The fact that many of the same therapies are used to treat both diseases emphasizes both their overlapping characteristics and the lack of targeted therapy. It is unclear if and how the topical or systemic therapies used in our patient to treat one disease affected the natural history of the other condition. It is important to highlight, however, that the patient had not been treated for months when he developed the psoriatic plaques with hair regrowth. Other case reports also document hair regrowth in untreated plaques,^13,16 making it unlikely to be a side effect of the medication regimen. For both psoriasis and AA, the immune cell composition and cytokine levels in the skin or serum vary throughout a patient’s disease course depending on severity of disease or response to treatment.^6,39,42,43 Therefore, we hypothesize that the 2 conditions interact in a similarly distinct manner based on each disease’s stage and intensity in the patient. Both our patient’s course thus far and the various presentations described by other groups support this hypothesis. Our patient had a small region of psoriasis on the scalp that cleared without any terminal hair growth. He also had larger plaques on the forearms that developed hair growth most predominantly within the thicker regions of the plaques. His unique presentation highlights the fluidity of the immune factors driving psoriasis vulgaris and AA.