Hair & Nails

The European Commission has authorized the marketing of ritlecitinib to treat adults and adolescents 12 years of age and older with severe alopecia areata. This makes ritlecitinib the first medicine authorized by the EC to treat individuals with severe alopecia areata as young as 12 years of age.

Taken as a once-daily pill, ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3. In June of 2023, the drug received FDA approval for the treatment of severe alopecia areata in people ages 12 and older in the United States.

According to a press release from Pfizer, which developed the drug, EC approval was based on the pivotal ALLEGRO clinical trial program, which included the ALLEGRO phase 2b/3 study that evaluated ritlecitinib in patients aged 12 years and older with alopecia areata with 50% or more scalp hair loss, including patients with alopecia totalis (total scalp hair loss) and alopecia universalis (total body hair loss). Results from this study showed that 13.4% of adults and adolescents achieved 90% or more scalp hair coverage (Severity of Alopecia Tool score of 10 or less) after 24 weeks of treatment with ritlecitinib 50 mg, compared with 1.5% of those on placebo.

The study also measured Patient Global Impression of Change (PGI-C). At week 24, 49.2% of participants treated with ritlecitinib reported a PGI-C response of “moderate” to “great” improvement in their alopecia areata, compared with 9.2% with placebo.

According to results from an ongoing, long-term phase 3 study of ritlecitinib known as ALLEGRO-LT, the most common adverse reactions reported from use of the drug included diarrhea (9.2%), acne (6.2%), upper respiratory tract infections (6.2%), urticaria (4.6%), rash (3.8%), folliculitis (3.1%), and dizziness (2.3%), the company press release said.





 

The European Commission has authorized the marketing of ritlecitinib to treat adults and adolescents 12 years of age and older with severe alopecia areata. This makes ritlecitinib the first medicine authorized by the EC to treat individuals with severe alopecia areata as young as 12 years of age.

Taken as a once-daily pill, ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3. In June of 2023, the drug received FDA approval for the treatment of severe alopecia areata in people ages 12 and older in the United States.

According to a press release from Pfizer, which developed the drug, EC approval was based on the pivotal ALLEGRO clinical trial program, which included the ALLEGRO phase 2b/3 study that evaluated ritlecitinib in patients aged 12 years and older with alopecia areata with 50% or more scalp hair loss, including patients with alopecia totalis (total scalp hair loss) and alopecia universalis (total body hair loss). Results from this study showed that 13.4% of adults and adolescents achieved 90% or more scalp hair coverage (Severity of Alopecia Tool score of 10 or less) after 24 weeks of treatment with ritlecitinib 50 mg, compared with 1.5% of those on placebo.

The study also measured Patient Global Impression of Change (PGI-C). At week 24, 49.2% of participants treated with ritlecitinib reported a PGI-C response of “moderate” to “great” improvement in their alopecia areata, compared with 9.2% with placebo.

According to results from an ongoing, long-term phase 3 study of ritlecitinib known as ALLEGRO-LT, the most common adverse reactions reported from use of the drug included diarrhea (9.2%), acne (6.2%), upper respiratory tract infections (6.2%), urticaria (4.6%), rash (3.8%), folliculitis (3.1%), and dizziness (2.3%), the company press release said.





 

The European Commission has authorized the marketing of ritlecitinib to treat adults and adolescents 12 years of age and older with severe alopecia areata. This makes ritlecitinib the first medicine authorized by the EC to treat individuals with severe alopecia areata as young as 12 years of age.

Taken as a once-daily pill, ritlecitinib is a dual inhibitor of the TEC family of tyrosine kinases and of Janus kinase 3. In June of 2023, the drug received FDA approval for the treatment of severe alopecia areata in people ages 12 and older in the United States.

According to a press release from Pfizer, which developed the drug, EC approval was based on the pivotal ALLEGRO clinical trial program, which included the ALLEGRO phase 2b/3 study that evaluated ritlecitinib in patients aged 12 years and older with alopecia areata with 50% or more scalp hair loss, including patients with alopecia totalis (total scalp hair loss) and alopecia universalis (total body hair loss). Results from this study showed that 13.4% of adults and adolescents achieved 90% or more scalp hair coverage (Severity of Alopecia Tool score of 10 or less) after 24 weeks of treatment with ritlecitinib 50 mg, compared with 1.5% of those on placebo.

The study also measured Patient Global Impression of Change (PGI-C). At week 24, 49.2% of participants treated with ritlecitinib reported a PGI-C response of “moderate” to “great” improvement in their alopecia areata, compared with 9.2% with placebo.

According to results from an ongoing, long-term phase 3 study of ritlecitinib known as ALLEGRO-LT, the most common adverse reactions reported from use of the drug included diarrhea (9.2%), acne (6.2%), upper respiratory tract infections (6.2%), urticaria (4.6%), rash (3.8%), folliculitis (3.1%), and dizziness (2.3%), the company press release said.





 

The Diagnosis: Congenital Cutaneous Langerhans Cell Histiocytosis

Although the infectious workup was positive for herpes simplex virus type 1 and cytomegalovirus antibodies, serologies for the rest of the TORCH (toxoplasmosis, other agents [syphilis, hepatitis B virus], rubella, cytomegalovirus) group of infections, as well as other bacterial, fungal, and viral infections, were negative. A skin biopsy from the right fifth toe showed a dense infiltrate of CD1a+ histiocytic cells with folded or kidney-shaped nuclei mixed with eosinophils, which was consistent with Langerhans cell histiocytosis (LCH) (Figure 1). Skin lesions were treated with hydrocortisone cream 2.5% and progressively faded over a few weeks.

Langerhans cell histiocytosis is a rare disorder with a variable clinical presentation depending on the sites affected and the extent of involvement. It can involve multiple organ systems, most commonly the skeletal system and the skin. Organ involvement is characterized by histiocyte infiltration. Acute disseminated multisystem disease most commonly is seen in children younger than 3 years.¹

Congenital cutaneous LCH presents with variable skin lesions ranging from papules to vesicles, pustules, and ulcers, with onset at birth or in the neonatal period. Various morphologic traits of skin lesions have been described; the most common presentation is multiple red to yellow-brown, crusted papules with accompanying hemorrhage or erosion.¹ Other cases have described an eczematous, seborrheic, diffuse eruption or erosive intertrigo. One case of a child with a solitary necrotic nodule on the scalp has been reported.²

Our patient presented with disseminated, nonblanching, purple to dark red papules and nodules of the skin and oral mucosa, as well as nail dystrophy (Figure 2). However, LCH in a neonate can mimic other causes of congenital papulonodular eruptions. Red-brown papules and nodules with or without crusting in a newborn can be mistaken for erythema toxicum neonatorum, transient neonatal pustular melanosis, congenital leukemia cutis, neonatal erythropoiesis, disseminated neonatal hemangiomatosis, infantile acropustulosis, or congenital TORCH infections such as rubella or syphilis. When LCH presents as vesicles or eroded papules or nodules in a newborn, the differential diagnosis includes incontinentia pigmenti and hereditary epidermolysis bullosa.

Langerhans cell histiocytosis may even present with a classic blueberry muffin rash that can lead clinicians to consider cutaneous metastasis from various hematologic malignancies or the more common TORCH infections. Several diagnostic tests can be performed to clarify the diagnosis, including bacterial and viral cultures and stains, serology, immunohistochemistry, flow cytometry, bone marrow aspiration, or skin biopsy.³ Langerhans cell histiocytosis is diagnosed with a combination of histology, immunohistochemistry, and clinical presentation; however, a skin biopsy is crucial. Tissue should be taken from the most easily accessible yet representative lesion. The characteristic appearance of LCH lesions is described as a dense infiltrate of histiocytic cells mixed with numerous eosinophils in the dermis.¹ Histiocytes usually have folded nuclei and eosinophilic cytoplasm or kidney-shaped nuclei with prominent nucleoli. Positive CD1a and/or CD207 (Langerin) staining of the cells is required for definitive diagnosis.⁴ After diagnosis, it is important to obtain baseline laboratory and radiographic studies to determine the extent of systemic involvement.

Treatment of congenital LCH is tailored to the extent of organ involvement. The dermatologic manifestations resolve without medications in many cases. However, true self-resolving LCH can only be diagnosed retrospectively after a full evaluation for other sites of disease. Disseminated disease can be life-threatening and requires more active management. In cases of skin-limited disease, therapies include topical steroids, nitrogen mustard, or imiquimod; surgical resection of isolated lesions; phototherapy; or systemic therapies such as methotrexate, 6-mercaptopurine, vinblastine/vincristine, cladribine, and/or cytarabine. Symptomatic patients initially are treated with methotrexate and 6-mercaptopurine.⁵ Asymptomatic infants with skin-limited involvement can be managed with topical treatments.

Our patient had skin-limited disease. Abdominal ultrasonography, skeletal survey, and magnetic resonance imaging of the brain revealed no abnormalities. The patient’s family was advised to monitor him for reoccurrence of the skin lesions and to continue close follow-up with hematology and dermatology. Although congenital LCH often is self-resolving, extensive skin involvement increases the risk for internal organ involvement for several years.⁶ These patients require long-term follow-up for potential musculoskeletal, ophthalmologic, endocrine, hepatic, and/or pulmonary disease.

The Diagnosis: Congenital Cutaneous Langerhans Cell Histiocytosis

Although the infectious workup was positive for herpes simplex virus type 1 and cytomegalovirus antibodies, serologies for the rest of the TORCH (toxoplasmosis, other agents [syphilis, hepatitis B virus], rubella, cytomegalovirus) group of infections, as well as other bacterial, fungal, and viral infections, were negative. A skin biopsy from the right fifth toe showed a dense infiltrate of CD1a+ histiocytic cells with folded or kidney-shaped nuclei mixed with eosinophils, which was consistent with Langerhans cell histiocytosis (LCH) (Figure 1). Skin lesions were treated with hydrocortisone cream 2.5% and progressively faded over a few weeks.

Langerhans cell histiocytosis is a rare disorder with a variable clinical presentation depending on the sites affected and the extent of involvement. It can involve multiple organ systems, most commonly the skeletal system and the skin. Organ involvement is characterized by histiocyte infiltration. Acute disseminated multisystem disease most commonly is seen in children younger than 3 years.¹

Congenital cutaneous LCH presents with variable skin lesions ranging from papules to vesicles, pustules, and ulcers, with onset at birth or in the neonatal period. Various morphologic traits of skin lesions have been described; the most common presentation is multiple red to yellow-brown, crusted papules with accompanying hemorrhage or erosion.¹ Other cases have described an eczematous, seborrheic, diffuse eruption or erosive intertrigo. One case of a child with a solitary necrotic nodule on the scalp has been reported.²

Our patient presented with disseminated, nonblanching, purple to dark red papules and nodules of the skin and oral mucosa, as well as nail dystrophy (Figure 2). However, LCH in a neonate can mimic other causes of congenital papulonodular eruptions. Red-brown papules and nodules with or without crusting in a newborn can be mistaken for erythema toxicum neonatorum, transient neonatal pustular melanosis, congenital leukemia cutis, neonatal erythropoiesis, disseminated neonatal hemangiomatosis, infantile acropustulosis, or congenital TORCH infections such as rubella or syphilis. When LCH presents as vesicles or eroded papules or nodules in a newborn, the differential diagnosis includes incontinentia pigmenti and hereditary epidermolysis bullosa.

Langerhans cell histiocytosis may even present with a classic blueberry muffin rash that can lead clinicians to consider cutaneous metastasis from various hematologic malignancies or the more common TORCH infections. Several diagnostic tests can be performed to clarify the diagnosis, including bacterial and viral cultures and stains, serology, immunohistochemistry, flow cytometry, bone marrow aspiration, or skin biopsy.³ Langerhans cell histiocytosis is diagnosed with a combination of histology, immunohistochemistry, and clinical presentation; however, a skin biopsy is crucial. Tissue should be taken from the most easily accessible yet representative lesion. The characteristic appearance of LCH lesions is described as a dense infiltrate of histiocytic cells mixed with numerous eosinophils in the dermis.¹ Histiocytes usually have folded nuclei and eosinophilic cytoplasm or kidney-shaped nuclei with prominent nucleoli. Positive CD1a and/or CD207 (Langerin) staining of the cells is required for definitive diagnosis.⁴ After diagnosis, it is important to obtain baseline laboratory and radiographic studies to determine the extent of systemic involvement.

Treatment of congenital LCH is tailored to the extent of organ involvement. The dermatologic manifestations resolve without medications in many cases. However, true self-resolving LCH can only be diagnosed retrospectively after a full evaluation for other sites of disease. Disseminated disease can be life-threatening and requires more active management. In cases of skin-limited disease, therapies include topical steroids, nitrogen mustard, or imiquimod; surgical resection of isolated lesions; phototherapy; or systemic therapies such as methotrexate, 6-mercaptopurine, vinblastine/vincristine, cladribine, and/or cytarabine. Symptomatic patients initially are treated with methotrexate and 6-mercaptopurine.⁵ Asymptomatic infants with skin-limited involvement can be managed with topical treatments.

Our patient had skin-limited disease. Abdominal ultrasonography, skeletal survey, and magnetic resonance imaging of the brain revealed no abnormalities. The patient’s family was advised to monitor him for reoccurrence of the skin lesions and to continue close follow-up with hematology and dermatology. Although congenital LCH often is self-resolving, extensive skin involvement increases the risk for internal organ involvement for several years.⁶ These patients require long-term follow-up for potential musculoskeletal, ophthalmologic, endocrine, hepatic, and/or pulmonary disease.

The Diagnosis: Congenital Cutaneous Langerhans Cell Histiocytosis

Although the infectious workup was positive for herpes simplex virus type 1 and cytomegalovirus antibodies, serologies for the rest of the TORCH (toxoplasmosis, other agents [syphilis, hepatitis B virus], rubella, cytomegalovirus) group of infections, as well as other bacterial, fungal, and viral infections, were negative. A skin biopsy from the right fifth toe showed a dense infiltrate of CD1a+ histiocytic cells with folded or kidney-shaped nuclei mixed with eosinophils, which was consistent with Langerhans cell histiocytosis (LCH) (Figure 1). Skin lesions were treated with hydrocortisone cream 2.5% and progressively faded over a few weeks.

Langerhans cell histiocytosis is a rare disorder with a variable clinical presentation depending on the sites affected and the extent of involvement. It can involve multiple organ systems, most commonly the skeletal system and the skin. Organ involvement is characterized by histiocyte infiltration. Acute disseminated multisystem disease most commonly is seen in children younger than 3 years.¹

Congenital cutaneous LCH presents with variable skin lesions ranging from papules to vesicles, pustules, and ulcers, with onset at birth or in the neonatal period. Various morphologic traits of skin lesions have been described; the most common presentation is multiple red to yellow-brown, crusted papules with accompanying hemorrhage or erosion.¹ Other cases have described an eczematous, seborrheic, diffuse eruption or erosive intertrigo. One case of a child with a solitary necrotic nodule on the scalp has been reported.²

Our patient presented with disseminated, nonblanching, purple to dark red papules and nodules of the skin and oral mucosa, as well as nail dystrophy (Figure 2). However, LCH in a neonate can mimic other causes of congenital papulonodular eruptions. Red-brown papules and nodules with or without crusting in a newborn can be mistaken for erythema toxicum neonatorum, transient neonatal pustular melanosis, congenital leukemia cutis, neonatal erythropoiesis, disseminated neonatal hemangiomatosis, infantile acropustulosis, or congenital TORCH infections such as rubella or syphilis. When LCH presents as vesicles or eroded papules or nodules in a newborn, the differential diagnosis includes incontinentia pigmenti and hereditary epidermolysis bullosa.

Langerhans cell histiocytosis may even present with a classic blueberry muffin rash that can lead clinicians to consider cutaneous metastasis from various hematologic malignancies or the more common TORCH infections. Several diagnostic tests can be performed to clarify the diagnosis, including bacterial and viral cultures and stains, serology, immunohistochemistry, flow cytometry, bone marrow aspiration, or skin biopsy.³ Langerhans cell histiocytosis is diagnosed with a combination of histology, immunohistochemistry, and clinical presentation; however, a skin biopsy is crucial. Tissue should be taken from the most easily accessible yet representative lesion. The characteristic appearance of LCH lesions is described as a dense infiltrate of histiocytic cells mixed with numerous eosinophils in the dermis.¹ Histiocytes usually have folded nuclei and eosinophilic cytoplasm or kidney-shaped nuclei with prominent nucleoli. Positive CD1a and/or CD207 (Langerin) staining of the cells is required for definitive diagnosis.⁴ After diagnosis, it is important to obtain baseline laboratory and radiographic studies to determine the extent of systemic involvement.

Treatment of congenital LCH is tailored to the extent of organ involvement. The dermatologic manifestations resolve without medications in many cases. However, true self-resolving LCH can only be diagnosed retrospectively after a full evaluation for other sites of disease. Disseminated disease can be life-threatening and requires more active management. In cases of skin-limited disease, therapies include topical steroids, nitrogen mustard, or imiquimod; surgical resection of isolated lesions; phototherapy; or systemic therapies such as methotrexate, 6-mercaptopurine, vinblastine/vincristine, cladribine, and/or cytarabine. Symptomatic patients initially are treated with methotrexate and 6-mercaptopurine.⁵ Asymptomatic infants with skin-limited involvement can be managed with topical treatments.

Our patient had skin-limited disease. Abdominal ultrasonography, skeletal survey, and magnetic resonance imaging of the brain revealed no abnormalities. The patient’s family was advised to monitor him for reoccurrence of the skin lesions and to continue close follow-up with hematology and dermatology. Although congenital LCH often is self-resolving, extensive skin involvement increases the risk for internal organ involvement for several years.⁶ These patients require long-term follow-up for potential musculoskeletal, ophthalmologic, endocrine, hepatic, and/or pulmonary disease.

Among patients with female pattern hair loss taking low-dose oral minoxidil (LDOM) for at least 4 months, minimal changes from baseline were observed in systolic blood pressure, diastolic blood pressure, and heart rate, results from a small retrospective analysis showed.

“Additionally, few patients experienced hair loss progression while slightly over a third experienced hair regrowth,” the study’s first author, Reese Imhof, MD, a third-year resident in the department of dermatology at Mayo Clinic, Rochester, Minn., said in an interview. The results were published online in JAAD International.

At low doses, oral minoxidil, approved as an antihypertensive over 40 years ago, has become an increasingly popular treatment for hair loss, particularly since an article about its use for hair loss was published in the New York Times in August 2022. (Oral minoxidil is not approved for treating alopecia, and is used off label for this purpose.)

To evaluate the effects of LDOM in female patients with female pattern hair loss, Dr. Imhof, along with colleagues Beija Villalpando, MD, of the department of medicine and Rochelle R. Torgerson, MD, PhD, of the department of dermatology at the Mayo Clinic, reviewed the records of 25 adult women who were evaluated for female pattern hair loss at the Mayo Clinic over a 5-year period that ended on Nov. 27, 2022. Previous studies have looked at the cardiovascular effects of treatment with oral minoxidil and impact on BP in men, but “few studies have reported on female patients receiving LDOM as monotherapy for female pattern hair loss,” the authors noted.

The mean age of the women in their study was 61 years, and they took LDOM for a mean of 6.2 months. Slightly more than half (52%) took a dose of 1.25 mg daily, while 40% took 2.5 mg daily and 8% took 0.625 mg daily.

Of the 25 patients, 10 (40%) had previously tried topical minoxidil but had discontinued it because of local side effects or challenges with adherence. Also, three patients (12%) had previously tried finasteride and spironolactone but discontinued those medications because of adverse side effects.

The researchers noted disease improvement and hair regrowth was observed in nine patients who were treated with LDOM (36%), while three patients (12%) had “unaltered disease progression.” Adverse side effects observed in the cohort included four patients with facial hypertrichosis (16%) and one patient with fluid retention/lower limb edema (4%).

The patients who developed hypertrichosis did not discontinue LDOM, but the patient who developed edema did stop treatment.

At baseline, systolic BP (SBP) ranged from 107-161 mm Hg, diastolic BP (DBP) ranged from 58-88 mm Hg, and heart rate ranged from 54-114 beats per minute. Post treatment, SBP ranged from 102-152 mm Hg, DBP ranged from 63-90 mm Hg, and heart rate ranged from 56 to 105 bpm. “It was surprising how little ambulatory blood pressure and heart rate changed after an average of 6 months of treatment,” Dr. Imhof said in an interview. “On average, SBP decreased by 2.8 mm HG while DBP decreased by 1.4 mm Hg. Heart rate increased an average of 4.4 beats per minute.”

He acknowledged certain limitations of the study, including its small sample size and lack of inclusion of patients who were being treated for hypertension with concomitant antihypertensive medications. “Some unique aspects of our study are that we focused on women, and we had a slightly older cohort than prior studies (61 years old on average) as well as exposure to higher doses of LDOM, with most patients on either 1.25 mg daily or 2.5 mg daily,” Dr. Imhof said.

The researchers reported having no relevant disclosures, and there was no funding source for the study.

Among patients with female pattern hair loss taking low-dose oral minoxidil (LDOM) for at least 4 months, minimal changes from baseline were observed in systolic blood pressure, diastolic blood pressure, and heart rate, results from a small retrospective analysis showed.

“Additionally, few patients experienced hair loss progression while slightly over a third experienced hair regrowth,” the study’s first author, Reese Imhof, MD, a third-year resident in the department of dermatology at Mayo Clinic, Rochester, Minn., said in an interview. The results were published online in JAAD International.

At low doses, oral minoxidil, approved as an antihypertensive over 40 years ago, has become an increasingly popular treatment for hair loss, particularly since an article about its use for hair loss was published in the New York Times in August 2022. (Oral minoxidil is not approved for treating alopecia, and is used off label for this purpose.)

To evaluate the effects of LDOM in female patients with female pattern hair loss, Dr. Imhof, along with colleagues Beija Villalpando, MD, of the department of medicine and Rochelle R. Torgerson, MD, PhD, of the department of dermatology at the Mayo Clinic, reviewed the records of 25 adult women who were evaluated for female pattern hair loss at the Mayo Clinic over a 5-year period that ended on Nov. 27, 2022. Previous studies have looked at the cardiovascular effects of treatment with oral minoxidil and impact on BP in men, but “few studies have reported on female patients receiving LDOM as monotherapy for female pattern hair loss,” the authors noted.

The mean age of the women in their study was 61 years, and they took LDOM for a mean of 6.2 months. Slightly more than half (52%) took a dose of 1.25 mg daily, while 40% took 2.5 mg daily and 8% took 0.625 mg daily.

Of the 25 patients, 10 (40%) had previously tried topical minoxidil but had discontinued it because of local side effects or challenges with adherence. Also, three patients (12%) had previously tried finasteride and spironolactone but discontinued those medications because of adverse side effects.

The researchers noted disease improvement and hair regrowth was observed in nine patients who were treated with LDOM (36%), while three patients (12%) had “unaltered disease progression.” Adverse side effects observed in the cohort included four patients with facial hypertrichosis (16%) and one patient with fluid retention/lower limb edema (4%).

The patients who developed hypertrichosis did not discontinue LDOM, but the patient who developed edema did stop treatment.

At baseline, systolic BP (SBP) ranged from 107-161 mm Hg, diastolic BP (DBP) ranged from 58-88 mm Hg, and heart rate ranged from 54-114 beats per minute. Post treatment, SBP ranged from 102-152 mm Hg, DBP ranged from 63-90 mm Hg, and heart rate ranged from 56 to 105 bpm. “It was surprising how little ambulatory blood pressure and heart rate changed after an average of 6 months of treatment,” Dr. Imhof said in an interview. “On average, SBP decreased by 2.8 mm HG while DBP decreased by 1.4 mm Hg. Heart rate increased an average of 4.4 beats per minute.”

He acknowledged certain limitations of the study, including its small sample size and lack of inclusion of patients who were being treated for hypertension with concomitant antihypertensive medications. “Some unique aspects of our study are that we focused on women, and we had a slightly older cohort than prior studies (61 years old on average) as well as exposure to higher doses of LDOM, with most patients on either 1.25 mg daily or 2.5 mg daily,” Dr. Imhof said.

The researchers reported having no relevant disclosures, and there was no funding source for the study.

Among patients with female pattern hair loss taking low-dose oral minoxidil (LDOM) for at least 4 months, minimal changes from baseline were observed in systolic blood pressure, diastolic blood pressure, and heart rate, results from a small retrospective analysis showed.

“Additionally, few patients experienced hair loss progression while slightly over a third experienced hair regrowth,” the study’s first author, Reese Imhof, MD, a third-year resident in the department of dermatology at Mayo Clinic, Rochester, Minn., said in an interview. The results were published online in JAAD International.

At low doses, oral minoxidil, approved as an antihypertensive over 40 years ago, has become an increasingly popular treatment for hair loss, particularly since an article about its use for hair loss was published in the New York Times in August 2022. (Oral minoxidil is not approved for treating alopecia, and is used off label for this purpose.)

To evaluate the effects of LDOM in female patients with female pattern hair loss, Dr. Imhof, along with colleagues Beija Villalpando, MD, of the department of medicine and Rochelle R. Torgerson, MD, PhD, of the department of dermatology at the Mayo Clinic, reviewed the records of 25 adult women who were evaluated for female pattern hair loss at the Mayo Clinic over a 5-year period that ended on Nov. 27, 2022. Previous studies have looked at the cardiovascular effects of treatment with oral minoxidil and impact on BP in men, but “few studies have reported on female patients receiving LDOM as monotherapy for female pattern hair loss,” the authors noted.

The mean age of the women in their study was 61 years, and they took LDOM for a mean of 6.2 months. Slightly more than half (52%) took a dose of 1.25 mg daily, while 40% took 2.5 mg daily and 8% took 0.625 mg daily.

Of the 25 patients, 10 (40%) had previously tried topical minoxidil but had discontinued it because of local side effects or challenges with adherence. Also, three patients (12%) had previously tried finasteride and spironolactone but discontinued those medications because of adverse side effects.

The researchers noted disease improvement and hair regrowth was observed in nine patients who were treated with LDOM (36%), while three patients (12%) had “unaltered disease progression.” Adverse side effects observed in the cohort included four patients with facial hypertrichosis (16%) and one patient with fluid retention/lower limb edema (4%).

The patients who developed hypertrichosis did not discontinue LDOM, but the patient who developed edema did stop treatment.

At baseline, systolic BP (SBP) ranged from 107-161 mm Hg, diastolic BP (DBP) ranged from 58-88 mm Hg, and heart rate ranged from 54-114 beats per minute. Post treatment, SBP ranged from 102-152 mm Hg, DBP ranged from 63-90 mm Hg, and heart rate ranged from 56 to 105 bpm. “It was surprising how little ambulatory blood pressure and heart rate changed after an average of 6 months of treatment,” Dr. Imhof said in an interview. “On average, SBP decreased by 2.8 mm HG while DBP decreased by 1.4 mm Hg. Heart rate increased an average of 4.4 beats per minute.”

He acknowledged certain limitations of the study, including its small sample size and lack of inclusion of patients who were being treated for hypertension with concomitant antihypertensive medications. “Some unique aspects of our study are that we focused on women, and we had a slightly older cohort than prior studies (61 years old on average) as well as exposure to higher doses of LDOM, with most patients on either 1.25 mg daily or 2.5 mg daily,” Dr. Imhof said.

The researchers reported having no relevant disclosures, and there was no funding source for the study.

If you’re looking to grow hair, you might just have a solution in your kitchen cabinet – if TikTok and some dermatologists are correct.

A small study published in 2015 suggested that rosemary oil may help regrow hair in people with androgenetic alopecia. The herb might also protect hair from the sun, pollution, and other environmental elements, according to an article in Insider.

The study published in Skinmed found that rosemary oil was similar to the effectiveness of minoxidil for regrowing hair in men with androgenetic alopecia. The scalp was also less itchy after 3-6 months of use.

The study included only men.

Still, dermatologist Shilpi Khetarpal, MD, told the Cleveland Clinic that it seems to work.

“The study really prompted people to look at rosemary oil for hair growth,” she said. “It became much more common in over-the-counter products after that, too.”

The Cleveland Clinic also reports that rosemary oil might help against dandruff and premature graying.

Dr. Khetarpal suggested massaging rosemary oil into the scalp, letting it soak overnight, and then washing it out. This should be done two or three times a week. 

She also noted that only a few drops of rosemary oil are needed, and that the focus should be on the scalp rather than the hair, which rosemary oil makes look greasy.

It may take 6 months for “meaningful improvement,” Dr. Khetarpal said.

Meanwhile, TikTok users love hyping the oil’s hair care qualities. On the social media platform, videos with the hashtag #rosemaryoil have been viewed more than 2 billion times.
 

A version of this article appeared on WebMD.com.

If you’re looking to grow hair, you might just have a solution in your kitchen cabinet – if TikTok and some dermatologists are correct.

A small study published in 2015 suggested that rosemary oil may help regrow hair in people with androgenetic alopecia. The herb might also protect hair from the sun, pollution, and other environmental elements, according to an article in Insider.

The study published in Skinmed found that rosemary oil was similar to the effectiveness of minoxidil for regrowing hair in men with androgenetic alopecia. The scalp was also less itchy after 3-6 months of use.

The study included only men.

Still, dermatologist Shilpi Khetarpal, MD, told the Cleveland Clinic that it seems to work.

“The study really prompted people to look at rosemary oil for hair growth,” she said. “It became much more common in over-the-counter products after that, too.”

The Cleveland Clinic also reports that rosemary oil might help against dandruff and premature graying.

Dr. Khetarpal suggested massaging rosemary oil into the scalp, letting it soak overnight, and then washing it out. This should be done two or three times a week. 

She also noted that only a few drops of rosemary oil are needed, and that the focus should be on the scalp rather than the hair, which rosemary oil makes look greasy.

It may take 6 months for “meaningful improvement,” Dr. Khetarpal said.

Meanwhile, TikTok users love hyping the oil’s hair care qualities. On the social media platform, videos with the hashtag #rosemaryoil have been viewed more than 2 billion times.
 

A version of this article appeared on WebMD.com.

If you’re looking to grow hair, you might just have a solution in your kitchen cabinet – if TikTok and some dermatologists are correct.

A small study published in 2015 suggested that rosemary oil may help regrow hair in people with androgenetic alopecia. The herb might also protect hair from the sun, pollution, and other environmental elements, according to an article in Insider.

The study published in Skinmed found that rosemary oil was similar to the effectiveness of minoxidil for regrowing hair in men with androgenetic alopecia. The scalp was also less itchy after 3-6 months of use.

The study included only men.

Still, dermatologist Shilpi Khetarpal, MD, told the Cleveland Clinic that it seems to work.

“The study really prompted people to look at rosemary oil for hair growth,” she said. “It became much more common in over-the-counter products after that, too.”

The Cleveland Clinic also reports that rosemary oil might help against dandruff and premature graying.

Dr. Khetarpal suggested massaging rosemary oil into the scalp, letting it soak overnight, and then washing it out. This should be done two or three times a week. 

She also noted that only a few drops of rosemary oil are needed, and that the focus should be on the scalp rather than the hair, which rosemary oil makes look greasy.

It may take 6 months for “meaningful improvement,” Dr. Khetarpal said.

Meanwhile, TikTok users love hyping the oil’s hair care qualities. On the social media platform, videos with the hashtag #rosemaryoil have been viewed more than 2 billion times.
 

A version of this article appeared on WebMD.com.

In a case series of 17 men with central centrifugal cicatricial alopecia (CCCA), almost half had a family history of alopecia, most were Black, and the most common symptom was scalp pruritus.

Researchers retrospectively reviewed the medical records of 17 male patients with a clinical diagnosis of CCCA who were seen at University of Pennsylvania outpatient clinics between 2012 and 2022. They excluded patients who had no scalp biopsy or if the scalp biopsy features limited characterization. Temitayo Ogunleye, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, led the study, published in the Journal of the American Academy of Dermatology.

CCCA, a type of scarring alopecia, most often affects women of African descent, and published data on the demographics, clinical findings, and medical histories of CCCA in men are limited, according to the authors.

The average age of the men was 43 years and 88.2% were Black, similar to women with CCCA, who tend to be middle-aged and Black. The four most common symptoms were scalp pruritus (58.8%), lesions (29.4%), pain or tenderness (23.5%), and hair thinning (23.5%). None of the men had type 2 diabetes (considered a possible CCCA risk factor), but 47.1% had a family history of alopecia. The four most common CCCA distributions were classic (47.1%), occipital (17.6%), patchy (11.8%), and posterior vertex (11.8%).

“Larger studies are needed to fully elucidate these relationships and explore etiology in males with CCCA,” the researchers wrote. “Nonetheless, we hope the data will prompt clinicians to assess for CCCA and risk factors in adult males with scarring alopecia.”

Limitations of the study included the retrospective, single-center design, and small sample size.

The researchers reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a case series of 17 men with central centrifugal cicatricial alopecia (CCCA), almost half had a family history of alopecia, most were Black, and the most common symptom was scalp pruritus.

Researchers retrospectively reviewed the medical records of 17 male patients with a clinical diagnosis of CCCA who were seen at University of Pennsylvania outpatient clinics between 2012 and 2022. They excluded patients who had no scalp biopsy or if the scalp biopsy features limited characterization. Temitayo Ogunleye, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, led the study, published in the Journal of the American Academy of Dermatology.

CCCA, a type of scarring alopecia, most often affects women of African descent, and published data on the demographics, clinical findings, and medical histories of CCCA in men are limited, according to the authors.

The average age of the men was 43 years and 88.2% were Black, similar to women with CCCA, who tend to be middle-aged and Black. The four most common symptoms were scalp pruritus (58.8%), lesions (29.4%), pain or tenderness (23.5%), and hair thinning (23.5%). None of the men had type 2 diabetes (considered a possible CCCA risk factor), but 47.1% had a family history of alopecia. The four most common CCCA distributions were classic (47.1%), occipital (17.6%), patchy (11.8%), and posterior vertex (11.8%).

“Larger studies are needed to fully elucidate these relationships and explore etiology in males with CCCA,” the researchers wrote. “Nonetheless, we hope the data will prompt clinicians to assess for CCCA and risk factors in adult males with scarring alopecia.”

Limitations of the study included the retrospective, single-center design, and small sample size.

The researchers reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In a case series of 17 men with central centrifugal cicatricial alopecia (CCCA), almost half had a family history of alopecia, most were Black, and the most common symptom was scalp pruritus.

Researchers retrospectively reviewed the medical records of 17 male patients with a clinical diagnosis of CCCA who were seen at University of Pennsylvania outpatient clinics between 2012 and 2022. They excluded patients who had no scalp biopsy or if the scalp biopsy features limited characterization. Temitayo Ogunleye, MD, of the department of dermatology, University of Pennsylvania, Philadelphia, led the study, published in the Journal of the American Academy of Dermatology.

CCCA, a type of scarring alopecia, most often affects women of African descent, and published data on the demographics, clinical findings, and medical histories of CCCA in men are limited, according to the authors.

The average age of the men was 43 years and 88.2% were Black, similar to women with CCCA, who tend to be middle-aged and Black. The four most common symptoms were scalp pruritus (58.8%), lesions (29.4%), pain or tenderness (23.5%), and hair thinning (23.5%). None of the men had type 2 diabetes (considered a possible CCCA risk factor), but 47.1% had a family history of alopecia. The four most common CCCA distributions were classic (47.1%), occipital (17.6%), patchy (11.8%), and posterior vertex (11.8%).

“Larger studies are needed to fully elucidate these relationships and explore etiology in males with CCCA,” the researchers wrote. “Nonetheless, we hope the data will prompt clinicians to assess for CCCA and risk factors in adult males with scarring alopecia.”

Limitations of the study included the retrospective, single-center design, and small sample size.

The researchers reported having no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Ferritin is an iron storage protein crucial to human iron homeostasis. Because serum ferritin levels are in dynamic equilibrium with the body’s iron stores, ferritin often is measured as a reflection of iron status; however, ferritin also is an acute-phase reactant whose levels may be nonspecifically elevated in a wide range of inflammatory conditions. The various processes that alter serum ferritin levels complicate the clinical interpretation of this laboratory value. In this article, we review the structure and function of ferritin and provide a guide for clinical use.

Overview of Iron

Iron is an essential element of key biologic functions including DNA synthesis and repair, oxygen transport, and oxidative phosphorylation. The body’s iron stores are mainly derived from internal iron recycling following red blood cell breakdown, while 5% to 10% is supplied by dietary intake.^1-3 Iron metabolism is of particular importance in cells of the reticuloendothelial system (eg, spleen, liver, bone marrow), where excess iron must be appropriately sequestered and from which iron can be mobilized.⁴ Sufficient iron stores are necessary for proper cellular function and survival, as iron is a necessary component of hemoglobin for oxygen delivery, iron-sulfur clusters in electron transport, and enzyme cofactors in other cellular processes.

Although labile pools of biologically active free iron exist in limited amounts within cells, excess free iron can generate free radicals that damage cellular proteins, lipids, and nucleic acids.^5-7 As such, most intracellular iron is captured within ferritin molecules. The excretion of iron is unregulated and occurs through loss in sweat, menstruation, hair shedding, skin desquamation, and enterocyte turnover.⁸ The lack of regulated excretion highlights the need for a tightly regulated system of uptake, transportation, storage, and sequestration to maintain iron homeostasis.

Overview of Ferritin Structure and Function

Ferritin is a key regulator of iron homeostasis that also serves as an important clinical indicator of body iron status. Ferritin mainly is found as an intracellular cytosolic iron storage and detoxification protein structured as a hollow 24-subunit polymer shell that can sequester up to 4500 atoms of iron within its core.^9,10 The 24-mer is composed of both ferritin L (FTL) and ferritin H (FTH) subunits, with dynamic regulation of the H:L ratio dependent on the context and tissue in which ferritin is found.⁶

Ferritin H possesses ferroxidase, which facilitates oxidation of ferrous (Fe²⁺) iron into ferric (Fe³⁺) iron, which can then be incorporated into the mineral core of the ferritin heteropolymer.¹¹ Ferritin L is more abundant in the spleen and liver, while FTH is found predominantly in the heart and kidneys where the increased ferroxidase activity may confer an increased ability to oxidize Fe²⁺ and limit oxidative stress.⁶

Regulation of Ferritin Synthesis and Secretion

Ferritin synthesis is regulated by intracellular nonheme iron levels, governed mainly by an iron response element (IRE) and iron response protein (IRP) translational repression system. Both FTH and FTL messenger RNA (mRNA) contain an IRE that is a regulatory stem-loop structure in the 5´ untranslated region. When the IRE is bound by IRP1 or IRP2, mRNA translation of ferritin subunits is suppressed.⁶ In low iron conditions, IRPs have greater affinity for IRE, and binding suppresses ferritin translation.¹² In high iron conditions, IRPs have a decreased affinity for IRE, and ferritin mRNA synthesis is increased.¹³ Additionally, inflammatory cytokines such as tumor necrosis factor α and IL-1α transcriptionally induce FTH synthesis, resulting in an increased population of H-rich ferritins.^11,14-16 A study using cultured human primary skin fibroblasts demonstrated UV radiation–induced increases in free intracellular iron content.^17,18 Pourzand et al¹⁸ suggested that UV-mediated damage of lysosomal membranes results in leakage of lysosomal proteases into the cytosol, contributing to degradation of intracellular ferritin and subsequent release of iron within skin fibroblasts. The increased intracellular iron downregulates IRPs and increases ferritin mRNA synthesis,¹⁸ consistent with prior findings of increased ferritin synthesis in skin that is induced by UV radiation.¹⁹

Molecular analysis of serum ferritin in iron-overloaded mice revealed that extracellular ferritin found in the serum is composed of a greater fraction of FTL and has lower iron content than intracellular ferritin. The low iron content of serum ferritin compared with intracellular ferritin and transferrin suggests that serum ferritin is not a major pathway of systemic iron transport.¹⁰ However, locally secreted ferritins may play a greater role in iron transport and release in selected tissues. Additionally, in vitro studies of cell cultures from humans and mice have demonstrated the ability of macrophages to secrete ferritin, suggesting that macrophages are an important cellular source of serum ferritin.^10,20 As such, serum ferritin generally may reflect body iron status but more specifically reflects macrophage iron status.¹⁰ Although the exact pathways of ferritin release are unknown, it is hypothesized that ferritin secretion occurs through cytosolic autophagy followed by secretion of proteins from the lysosomal compartment.^10,18,21

Low Ferritin and Iron Deficiency—Although bone marrow biopsy with iron staining remains the gold standard for diagnosis of iron deficiency, serum ferritin is a much more accessible and less invasive tool for evaluation of iron status. A serum ferritin level below 12 μg/L is highly specific for iron depletion,²² with a higher cutoff recommended in clinical practice to improve diagnostic sensitivity.^23,24 Conditions independent of iron deficiency that may reduce serum ferritin include hypothyroidism and ascorbate deficiency, though neither condition has been reported to interfere with appropriate diagnosis of iron deficiency.²⁵ Guyatt et al²⁶ conducted a systematic review of laboratory tests used in the diagnosis of iron deficiency anemia and identified 55 studies suitable for inclusion. Based on an area under the receiver operating characteristic curve (AUROC) of 0.95, serum ferritin values were superior to transferrin saturation (AUROC, 0.74), red cell protoporphyrin (AUROC, 0.77), red cell volume distribution width (AUROC, 0.62), and mean cell volume (AUROC, 0.76) for diagnosis of IDA, verified by histologic examination of aspirated bone marrow.²⁶ The likelihood ratio of iron deficiency begins to decrease for serum ferritin values of 40 μg/L or greater. For patients with inflammatory conditions—patients with concomitant chronic renal failure, inflammatory disease, infection, rheumatoid arthritis, liver disease, inflammatory bowel disease, and malignancy—the likelihood of iron deficiency begins to decrease at serum ferritin levels of 70 μg/L or greater.²⁶ Similarly, the World Health Organization recommends that in adults with infection or inflammation, serum ferritin levels lower than 70 μg/L may be used to indicate iron deficiency.²⁴ A serum ferritin level of 41 μg/L or lower was found to have a sensitivity and specificity of 98% for discriminating between iron-deficiency anemia and anemia of chronic disease (diagnosed based on bone marrow biopsy with iron staining), with an AUROC of 0.98.²⁷ As such, we recommend using a serum ferritin level of 40 μg/L or lower in patients who are otherwise healthy as an indicator of iron deficiency.

The threshold for iron supplementation may vary based on age, sex, and race. In women, ferritin levels increase during menopause and peak after menopause; ferritin levels are higher in men than in women.^28-30 A multisite longitudinal cohort study of 70 women in the United States found that the mean (SD) ferritin valuewas 69.5 (81.7) μg/L premenopause and 128.8 (125.7) μg/L postmenopause (P<.01).³¹ A separate longitudinal survey study of 8564 patients in China found that the mean (SE) ferritin value was 201.55 (3.60) μg/L for men and 80.46 (1.64) μg/L for women (P<.0001).³² Analysis of serum ferritin levels of 3554 male patients from the third National Health and Nutrition Examination Survey demonstrated that patients who self-reported as non-Hispanic Black (n=1616) had significantly higher serum ferritin levels than non-Hispanic White patients (n=1938)(serum ferritin difference of 37.1 μg/L)(P<.0001).³³ The British Society for Haematology guidelines recommend that the threshold of serum ferritin for diagnosing iron deficiency should take into account age-, sex-, and race-based differences.³⁴ Ferritin and Hair—Cutaneous manifestations of iron deficiency include koilonychia, glossitis, pruritus, angular cheilitis, and telogen effluvium (TE).¹ A case-control study of 30 females aged 15 to 45 years demonstrated that the mean (SD) ferritin level was significantly lower in patients with TE than those with no hair loss (16.3 [12.6] ng/mL vs 60.3 [50.1] ng/mL; P<.0001). Using a threshold of 30 μg/L or lower, the investigators found that the odds ratio for TE was 21.0 (95% CI, 4.2-105.0) in patients with low serum ferritin.³⁵

Another retrospective review of 54 patients with diffuse hair loss and 55 controls compared serum vitamin B₁₂, folate, thyroid-stimulating hormone, zinc, ferritin, and 25-hydroxy vitamin D levels between the 2 groups.³⁶ Exclusion criteria were clinical diagnoses of female pattern hair loss (androgenetic alopecia), pregnancy, menopause, metabolic and endocrine disorders, hormone replacement therapy, chemotherapy, immunosuppressive therapy, vitamin and mineral supplementation, scarring alopecia, eating disorders, and restrictive diets. Compared with controls, patients with diffuse nonscarring hair loss were found to have significantly lower ferritin (mean [SD], 14.72 [10.70] ng/mL vs 25.30 [14.41] ng/mL; P<.001) and 25-hydroxy vitamin D levels (mean [SD], 14.03 [8.09] ng/mL vs 17.01 [8.59] ng/mL; P=.01).³⁶

In contrast, a separate case-control study of 381 cases and 76 controls found no increase in the rate of iron deficiency—defined as ferritin ≤15 μg/L or ≤40 μg/L—among women with female pattern hair loss or chronic TE vs controls.³⁷ Taken together, these studies suggest that iron status may play a role in TE, a process that may result from nutritional deficiency, trauma, or physical or psychological stress³⁸; however, there is insufficient evidence to suggest that low iron status impacts androgenetic alopecia, in which its multifactorial pathogenesis implicates genetic and hormonal factors.³⁹ More research is needed to clarify the potential associations between iron deficiency and types of hair loss. Additionally, it is unclear whether iron supplementation improves hair growth parameters such as density and caliber.⁴⁰

Low serum ferritin (<40 μg/L) with concurrent symptoms of iron deficiency, including fatigue, pallor, dyspnea on exertion, or hair loss, should prompt treatment with supplemental iron.^41-43 Generally, ferrous (Fe2⁺) salts are preferred to ferric (Fe3⁺) salts, as the former is more readily absorbed through the duodenal mucosa⁴⁴ and is the more common formulation in commercially available supplements in the United States.⁴⁵ Oral supplementation with ferrous sulfate 325 mg (65 mg elemental iron) tablets is the first-line therapy for iron deficiency anemia.¹ Alternatively, ferrous gluconate 324 mg (38 mg elemental iron) over-the-counter and its liquid form has demonstrated superior absorption compared to ferrous sulfate tablets in a clinical study with peritoneal dialysis patients.^1,46 One study suggested that oral iron 40 to 80 mg should be taken every other day to increase absorption.⁴⁷ Due to improved bioavailability, intravenous iron may be utilized in patients with malabsorption, renal failure, or intolerance to oral iron (including those with gastric ulcers or active inflammatory bowel disease), with the formulation chosen based on underlying comorbidities and potential risks.^1,48 The theoretical risk for potentiating bacterial growth by increasing the amount of unbound iron in the blood raises concerns of iron supplementation in patients with infection or sepsis. Although far from definitive, existing data suggest that risk for infection is greater with intravenous iron supplementation and should be carefully considered prior to use.^49,50Elevated Ferritin—Elevated ferritin may be difficult to interpret given the multitude of conditions that can cause it.^23,51,52 Elevated serum ferritin can be broadly characterized by increased synthesis due to iron overload, increased synthesis due to inflammation, or increased ferritin release from cellular damage.³⁴ Further complicating interpretation is the potential diurnal fluctuations in serum iron levels dependent on dietary intake and timing of laboratory evaluation, choice of assay, differences in reference standards, and variations in calibration procedures that can lead to analytic variability in the measurement of ferritin.^23,53,54

Among healthy patients, serum ferritin is directly proportional to iron status.^9,51 A study utilizing weekly phlebotomy of 22 healthy participants to measure serum ferritin and calculate mobilizable storage iron found a strong positive correlation between the 2 variables (r=0.83, P<.001), with each 1-μg/L increase of serum ferritin corresponding to approximately an 8-mg increase of storage iron; the initial serum ferritin values ranged from 2 to 83 μg/L in females and 36 to 224 μg/L in males.⁵⁵ The correlation of ferritin with iron status also was supported by the significant correlation between the number of transfusions received in patients with transfusion-related iron overload and serum ferritin levels (r=0.89, P<.001), with an average increase of 60 μg/L per transfusion.⁵¹

Clinical guidelines on the interpretation of serum ferritin levels by Cullis et al³⁴ recommend a normal upper limit of 200 μg/L for healthy females and 300 μg/L for healthy males. Outside of clinical syndromes associated with iron overload, Lee and Means⁵⁶ found that serum ferritin of 1000 μg/L or higher was a nonspecific marker of disease, including infection and/or neoplastic disorders. We have adapted these guidelines to propose a workflow for evaluation of serum ferritin levels (Figure). In patients with inflammatory conditions or those affected by metabolic syndrome, elevated serum ferritin does not correlate with body iron status.^57,58 It is believed that inflammatory cytokines, including tumor necrosis factor α and IL-1α, can upregulate ferritin synthesis independent of cellular iron stores.^15,16 Several studies have examined the relationship between insulin resistance and/or metabolic syndrome with serum ferritin levels.^31,32 Han et al³² found that elevated serum ferritin was significantly associated with higher risk for metabolic syndrome in men (P<.0001) but not in women.

Although cutaneous manifestations of iron overload can be seen as skin hyperpigmentation due to increased iron deposits and increased melanin production,²² the effects of elevated ferritin on the skin and hair are not well known. Iron overload is a known trigger of porphyria cutanea tarda (PCT),⁵⁹ a condition in which reduced or absent enzymatic activity of uroporphyrinogen decarboxylase (UROD) leads to build up of toxic porphyrins in various organs.⁶⁰ In the skin, PCT manifests as a blistering photosensitive eruption that may resolve as dyspigmentation, scarring, and milia.⁶¹ Phlebotomy is first-line therapy in PCT to reduce serum iron and subsequent formation of UROD inhibitors, with guidelines suggesting discontinuation of phlebotomy when serum ferritin levels reach 20 ng/mL or lower.⁶⁰ Hyperferritinemia (serum ferritin >500 μg/L) is a common finding in several inflammatory disorders often accompanied by clinically apparent cutaneous symptoms such as adult-onset Still disease,⁶² hemophagocytic lymphohistiocytosis,^63,64 and anti-melanoma differentiation-associated gene 5 dermatomyositis.⁶⁵ Among these conditions, serum ferritin levels have been reported to correlate with disease activity, raising the question of whether ferritin is a bystander or a driver of the underlying pathology.^62,66,67 However, rapid decline of serum ferritin levels with treatment and control of inflammatory cytokines suggest that ferritin is unlikely to contribute to pathology.^62,67

Final Thoughts

Many clinical studies have examined the association between hair health and body iron status, the collective findings of which suggest that iron deficiency may be associated with TE. Among commonly measured serum iron parameters, low ferritin is a highly specific and sensitive marker for diagnosing iron deficiency. Serum ferritin may be a clinically useful tool for ruling out underlying iron deficiency in patients presenting with hair loss. Despite advances in our understanding of the molecular mechanisms of ferritin synthesis and regulation, whether ferritin itself contributes to cutaneous pathology is poorly understood.^35,36,68-74 For patients who are otherwise healthy with low suspicion for inflammatory disorders, chronic systemic illnesses, or malignancy, serum ferritin can be used as an indicator of body iron status. The workup for slightly elevated serum ferritin should be interpreted in the context of other laboratory findings and should be reassessed over time. Serum ferritin levels above 1000 μg/L warrant further investigation into causes such as iron overload conditions and underlying inflammatory conditions or malignancy.

Ferritin is an iron storage protein crucial to human iron homeostasis. Because serum ferritin levels are in dynamic equilibrium with the body’s iron stores, ferritin often is measured as a reflection of iron status; however, ferritin also is an acute-phase reactant whose levels may be nonspecifically elevated in a wide range of inflammatory conditions. The various processes that alter serum ferritin levels complicate the clinical interpretation of this laboratory value. In this article, we review the structure and function of ferritin and provide a guide for clinical use.

Overview of Iron

Iron is an essential element of key biologic functions including DNA synthesis and repair, oxygen transport, and oxidative phosphorylation. The body’s iron stores are mainly derived from internal iron recycling following red blood cell breakdown, while 5% to 10% is supplied by dietary intake.^1-3 Iron metabolism is of particular importance in cells of the reticuloendothelial system (eg, spleen, liver, bone marrow), where excess iron must be appropriately sequestered and from which iron can be mobilized.⁴ Sufficient iron stores are necessary for proper cellular function and survival, as iron is a necessary component of hemoglobin for oxygen delivery, iron-sulfur clusters in electron transport, and enzyme cofactors in other cellular processes.

Although labile pools of biologically active free iron exist in limited amounts within cells, excess free iron can generate free radicals that damage cellular proteins, lipids, and nucleic acids.^5-7 As such, most intracellular iron is captured within ferritin molecules. The excretion of iron is unregulated and occurs through loss in sweat, menstruation, hair shedding, skin desquamation, and enterocyte turnover.⁸ The lack of regulated excretion highlights the need for a tightly regulated system of uptake, transportation, storage, and sequestration to maintain iron homeostasis.

Overview of Ferritin Structure and Function

Ferritin is a key regulator of iron homeostasis that also serves as an important clinical indicator of body iron status. Ferritin mainly is found as an intracellular cytosolic iron storage and detoxification protein structured as a hollow 24-subunit polymer shell that can sequester up to 4500 atoms of iron within its core.^9,10 The 24-mer is composed of both ferritin L (FTL) and ferritin H (FTH) subunits, with dynamic regulation of the H:L ratio dependent on the context and tissue in which ferritin is found.⁶

Ferritin H possesses ferroxidase, which facilitates oxidation of ferrous (Fe²⁺) iron into ferric (Fe³⁺) iron, which can then be incorporated into the mineral core of the ferritin heteropolymer.¹¹ Ferritin L is more abundant in the spleen and liver, while FTH is found predominantly in the heart and kidneys where the increased ferroxidase activity may confer an increased ability to oxidize Fe²⁺ and limit oxidative stress.⁶

Regulation of Ferritin Synthesis and Secretion

Ferritin synthesis is regulated by intracellular nonheme iron levels, governed mainly by an iron response element (IRE) and iron response protein (IRP) translational repression system. Both FTH and FTL messenger RNA (mRNA) contain an IRE that is a regulatory stem-loop structure in the 5´ untranslated region. When the IRE is bound by IRP1 or IRP2, mRNA translation of ferritin subunits is suppressed.⁶ In low iron conditions, IRPs have greater affinity for IRE, and binding suppresses ferritin translation.¹² In high iron conditions, IRPs have a decreased affinity for IRE, and ferritin mRNA synthesis is increased.¹³ Additionally, inflammatory cytokines such as tumor necrosis factor α and IL-1α transcriptionally induce FTH synthesis, resulting in an increased population of H-rich ferritins.^11,14-16 A study using cultured human primary skin fibroblasts demonstrated UV radiation–induced increases in free intracellular iron content.^17,18 Pourzand et al¹⁸ suggested that UV-mediated damage of lysosomal membranes results in leakage of lysosomal proteases into the cytosol, contributing to degradation of intracellular ferritin and subsequent release of iron within skin fibroblasts. The increased intracellular iron downregulates IRPs and increases ferritin mRNA synthesis,¹⁸ consistent with prior findings of increased ferritin synthesis in skin that is induced by UV radiation.¹⁹

Molecular analysis of serum ferritin in iron-overloaded mice revealed that extracellular ferritin found in the serum is composed of a greater fraction of FTL and has lower iron content than intracellular ferritin. The low iron content of serum ferritin compared with intracellular ferritin and transferrin suggests that serum ferritin is not a major pathway of systemic iron transport.¹⁰ However, locally secreted ferritins may play a greater role in iron transport and release in selected tissues. Additionally, in vitro studies of cell cultures from humans and mice have demonstrated the ability of macrophages to secrete ferritin, suggesting that macrophages are an important cellular source of serum ferritin.^10,20 As such, serum ferritin generally may reflect body iron status but more specifically reflects macrophage iron status.¹⁰ Although the exact pathways of ferritin release are unknown, it is hypothesized that ferritin secretion occurs through cytosolic autophagy followed by secretion of proteins from the lysosomal compartment.^10,18,21

Low Ferritin and Iron Deficiency—Although bone marrow biopsy with iron staining remains the gold standard for diagnosis of iron deficiency, serum ferritin is a much more accessible and less invasive tool for evaluation of iron status. A serum ferritin level below 12 μg/L is highly specific for iron depletion,²² with a higher cutoff recommended in clinical practice to improve diagnostic sensitivity.^23,24 Conditions independent of iron deficiency that may reduce serum ferritin include hypothyroidism and ascorbate deficiency, though neither condition has been reported to interfere with appropriate diagnosis of iron deficiency.²⁵ Guyatt et al²⁶ conducted a systematic review of laboratory tests used in the diagnosis of iron deficiency anemia and identified 55 studies suitable for inclusion. Based on an area under the receiver operating characteristic curve (AUROC) of 0.95, serum ferritin values were superior to transferrin saturation (AUROC, 0.74), red cell protoporphyrin (AUROC, 0.77), red cell volume distribution width (AUROC, 0.62), and mean cell volume (AUROC, 0.76) for diagnosis of IDA, verified by histologic examination of aspirated bone marrow.²⁶ The likelihood ratio of iron deficiency begins to decrease for serum ferritin values of 40 μg/L or greater. For patients with inflammatory conditions—patients with concomitant chronic renal failure, inflammatory disease, infection, rheumatoid arthritis, liver disease, inflammatory bowel disease, and malignancy—the likelihood of iron deficiency begins to decrease at serum ferritin levels of 70 μg/L or greater.²⁶ Similarly, the World Health Organization recommends that in adults with infection or inflammation, serum ferritin levels lower than 70 μg/L may be used to indicate iron deficiency.²⁴ A serum ferritin level of 41 μg/L or lower was found to have a sensitivity and specificity of 98% for discriminating between iron-deficiency anemia and anemia of chronic disease (diagnosed based on bone marrow biopsy with iron staining), with an AUROC of 0.98.²⁷ As such, we recommend using a serum ferritin level of 40 μg/L or lower in patients who are otherwise healthy as an indicator of iron deficiency.

The threshold for iron supplementation may vary based on age, sex, and race. In women, ferritin levels increase during menopause and peak after menopause; ferritin levels are higher in men than in women.^28-30 A multisite longitudinal cohort study of 70 women in the United States found that the mean (SD) ferritin valuewas 69.5 (81.7) μg/L premenopause and 128.8 (125.7) μg/L postmenopause (P<.01).³¹ A separate longitudinal survey study of 8564 patients in China found that the mean (SE) ferritin value was 201.55 (3.60) μg/L for men and 80.46 (1.64) μg/L for women (P<.0001).³² Analysis of serum ferritin levels of 3554 male patients from the third National Health and Nutrition Examination Survey demonstrated that patients who self-reported as non-Hispanic Black (n=1616) had significantly higher serum ferritin levels than non-Hispanic White patients (n=1938)(serum ferritin difference of 37.1 μg/L)(P<.0001).³³ The British Society for Haematology guidelines recommend that the threshold of serum ferritin for diagnosing iron deficiency should take into account age-, sex-, and race-based differences.³⁴ Ferritin and Hair—Cutaneous manifestations of iron deficiency include koilonychia, glossitis, pruritus, angular cheilitis, and telogen effluvium (TE).¹ A case-control study of 30 females aged 15 to 45 years demonstrated that the mean (SD) ferritin level was significantly lower in patients with TE than those with no hair loss (16.3 [12.6] ng/mL vs 60.3 [50.1] ng/mL; P<.0001). Using a threshold of 30 μg/L or lower, the investigators found that the odds ratio for TE was 21.0 (95% CI, 4.2-105.0) in patients with low serum ferritin.³⁵

Another retrospective review of 54 patients with diffuse hair loss and 55 controls compared serum vitamin B₁₂, folate, thyroid-stimulating hormone, zinc, ferritin, and 25-hydroxy vitamin D levels between the 2 groups.³⁶ Exclusion criteria were clinical diagnoses of female pattern hair loss (androgenetic alopecia), pregnancy, menopause, metabolic and endocrine disorders, hormone replacement therapy, chemotherapy, immunosuppressive therapy, vitamin and mineral supplementation, scarring alopecia, eating disorders, and restrictive diets. Compared with controls, patients with diffuse nonscarring hair loss were found to have significantly lower ferritin (mean [SD], 14.72 [10.70] ng/mL vs 25.30 [14.41] ng/mL; P<.001) and 25-hydroxy vitamin D levels (mean [SD], 14.03 [8.09] ng/mL vs 17.01 [8.59] ng/mL; P=.01).³⁶

In contrast, a separate case-control study of 381 cases and 76 controls found no increase in the rate of iron deficiency—defined as ferritin ≤15 μg/L or ≤40 μg/L—among women with female pattern hair loss or chronic TE vs controls.³⁷ Taken together, these studies suggest that iron status may play a role in TE, a process that may result from nutritional deficiency, trauma, or physical or psychological stress³⁸; however, there is insufficient evidence to suggest that low iron status impacts androgenetic alopecia, in which its multifactorial pathogenesis implicates genetic and hormonal factors.³⁹ More research is needed to clarify the potential associations between iron deficiency and types of hair loss. Additionally, it is unclear whether iron supplementation improves hair growth parameters such as density and caliber.⁴⁰

Low serum ferritin (<40 μg/L) with concurrent symptoms of iron deficiency, including fatigue, pallor, dyspnea on exertion, or hair loss, should prompt treatment with supplemental iron.^41-43 Generally, ferrous (Fe2⁺) salts are preferred to ferric (Fe3⁺) salts, as the former is more readily absorbed through the duodenal mucosa⁴⁴ and is the more common formulation in commercially available supplements in the United States.⁴⁵ Oral supplementation with ferrous sulfate 325 mg (65 mg elemental iron) tablets is the first-line therapy for iron deficiency anemia.¹ Alternatively, ferrous gluconate 324 mg (38 mg elemental iron) over-the-counter and its liquid form has demonstrated superior absorption compared to ferrous sulfate tablets in a clinical study with peritoneal dialysis patients.^1,46 One study suggested that oral iron 40 to 80 mg should be taken every other day to increase absorption.⁴⁷ Due to improved bioavailability, intravenous iron may be utilized in patients with malabsorption, renal failure, or intolerance to oral iron (including those with gastric ulcers or active inflammatory bowel disease), with the formulation chosen based on underlying comorbidities and potential risks.^1,48 The theoretical risk for potentiating bacterial growth by increasing the amount of unbound iron in the blood raises concerns of iron supplementation in patients with infection or sepsis. Although far from definitive, existing data suggest that risk for infection is greater with intravenous iron supplementation and should be carefully considered prior to use.^49,50Elevated Ferritin—Elevated ferritin may be difficult to interpret given the multitude of conditions that can cause it.^23,51,52 Elevated serum ferritin can be broadly characterized by increased synthesis due to iron overload, increased synthesis due to inflammation, or increased ferritin release from cellular damage.³⁴ Further complicating interpretation is the potential diurnal fluctuations in serum iron levels dependent on dietary intake and timing of laboratory evaluation, choice of assay, differences in reference standards, and variations in calibration procedures that can lead to analytic variability in the measurement of ferritin.^23,53,54

Among healthy patients, serum ferritin is directly proportional to iron status.^9,51 A study utilizing weekly phlebotomy of 22 healthy participants to measure serum ferritin and calculate mobilizable storage iron found a strong positive correlation between the 2 variables (r=0.83, P<.001), with each 1-μg/L increase of serum ferritin corresponding to approximately an 8-mg increase of storage iron; the initial serum ferritin values ranged from 2 to 83 μg/L in females and 36 to 224 μg/L in males.⁵⁵ The correlation of ferritin with iron status also was supported by the significant correlation between the number of transfusions received in patients with transfusion-related iron overload and serum ferritin levels (r=0.89, P<.001), with an average increase of 60 μg/L per transfusion.⁵¹

Clinical guidelines on the interpretation of serum ferritin levels by Cullis et al³⁴ recommend a normal upper limit of 200 μg/L for healthy females and 300 μg/L for healthy males. Outside of clinical syndromes associated with iron overload, Lee and Means⁵⁶ found that serum ferritin of 1000 μg/L or higher was a nonspecific marker of disease, including infection and/or neoplastic disorders. We have adapted these guidelines to propose a workflow for evaluation of serum ferritin levels (Figure). In patients with inflammatory conditions or those affected by metabolic syndrome, elevated serum ferritin does not correlate with body iron status.^57,58 It is believed that inflammatory cytokines, including tumor necrosis factor α and IL-1α, can upregulate ferritin synthesis independent of cellular iron stores.^15,16 Several studies have examined the relationship between insulin resistance and/or metabolic syndrome with serum ferritin levels.^31,32 Han et al³² found that elevated serum ferritin was significantly associated with higher risk for metabolic syndrome in men (P<.0001) but not in women.

Although cutaneous manifestations of iron overload can be seen as skin hyperpigmentation due to increased iron deposits and increased melanin production,²² the effects of elevated ferritin on the skin and hair are not well known. Iron overload is a known trigger of porphyria cutanea tarda (PCT),⁵⁹ a condition in which reduced or absent enzymatic activity of uroporphyrinogen decarboxylase (UROD) leads to build up of toxic porphyrins in various organs.⁶⁰ In the skin, PCT manifests as a blistering photosensitive eruption that may resolve as dyspigmentation, scarring, and milia.⁶¹ Phlebotomy is first-line therapy in PCT to reduce serum iron and subsequent formation of UROD inhibitors, with guidelines suggesting discontinuation of phlebotomy when serum ferritin levels reach 20 ng/mL or lower.⁶⁰ Hyperferritinemia (serum ferritin >500 μg/L) is a common finding in several inflammatory disorders often accompanied by clinically apparent cutaneous symptoms such as adult-onset Still disease,⁶² hemophagocytic lymphohistiocytosis,^63,64 and anti-melanoma differentiation-associated gene 5 dermatomyositis.⁶⁵ Among these conditions, serum ferritin levels have been reported to correlate with disease activity, raising the question of whether ferritin is a bystander or a driver of the underlying pathology.^62,66,67 However, rapid decline of serum ferritin levels with treatment and control of inflammatory cytokines suggest that ferritin is unlikely to contribute to pathology.^62,67

Final Thoughts

Many clinical studies have examined the association between hair health and body iron status, the collective findings of which suggest that iron deficiency may be associated with TE. Among commonly measured serum iron parameters, low ferritin is a highly specific and sensitive marker for diagnosing iron deficiency. Serum ferritin may be a clinically useful tool for ruling out underlying iron deficiency in patients presenting with hair loss. Despite advances in our understanding of the molecular mechanisms of ferritin synthesis and regulation, whether ferritin itself contributes to cutaneous pathology is poorly understood.^35,36,68-74 For patients who are otherwise healthy with low suspicion for inflammatory disorders, chronic systemic illnesses, or malignancy, serum ferritin can be used as an indicator of body iron status. The workup for slightly elevated serum ferritin should be interpreted in the context of other laboratory findings and should be reassessed over time. Serum ferritin levels above 1000 μg/L warrant further investigation into causes such as iron overload conditions and underlying inflammatory conditions or malignancy.

Ferritin is an iron storage protein crucial to human iron homeostasis. Because serum ferritin levels are in dynamic equilibrium with the body’s iron stores, ferritin often is measured as a reflection of iron status; however, ferritin also is an acute-phase reactant whose levels may be nonspecifically elevated in a wide range of inflammatory conditions. The various processes that alter serum ferritin levels complicate the clinical interpretation of this laboratory value. In this article, we review the structure and function of ferritin and provide a guide for clinical use.

Overview of Iron

Iron is an essential element of key biologic functions including DNA synthesis and repair, oxygen transport, and oxidative phosphorylation. The body’s iron stores are mainly derived from internal iron recycling following red blood cell breakdown, while 5% to 10% is supplied by dietary intake.^1-3 Iron metabolism is of particular importance in cells of the reticuloendothelial system (eg, spleen, liver, bone marrow), where excess iron must be appropriately sequestered and from which iron can be mobilized.⁴ Sufficient iron stores are necessary for proper cellular function and survival, as iron is a necessary component of hemoglobin for oxygen delivery, iron-sulfur clusters in electron transport, and enzyme cofactors in other cellular processes.

Although labile pools of biologically active free iron exist in limited amounts within cells, excess free iron can generate free radicals that damage cellular proteins, lipids, and nucleic acids.^5-7 As such, most intracellular iron is captured within ferritin molecules. The excretion of iron is unregulated and occurs through loss in sweat, menstruation, hair shedding, skin desquamation, and enterocyte turnover.⁸ The lack of regulated excretion highlights the need for a tightly regulated system of uptake, transportation, storage, and sequestration to maintain iron homeostasis.

Overview of Ferritin Structure and Function

Ferritin is a key regulator of iron homeostasis that also serves as an important clinical indicator of body iron status. Ferritin mainly is found as an intracellular cytosolic iron storage and detoxification protein structured as a hollow 24-subunit polymer shell that can sequester up to 4500 atoms of iron within its core.^9,10 The 24-mer is composed of both ferritin L (FTL) and ferritin H (FTH) subunits, with dynamic regulation of the H:L ratio dependent on the context and tissue in which ferritin is found.⁶

Ferritin H possesses ferroxidase, which facilitates oxidation of ferrous (Fe²⁺) iron into ferric (Fe³⁺) iron, which can then be incorporated into the mineral core of the ferritin heteropolymer.¹¹ Ferritin L is more abundant in the spleen and liver, while FTH is found predominantly in the heart and kidneys where the increased ferroxidase activity may confer an increased ability to oxidize Fe²⁺ and limit oxidative stress.⁶

Regulation of Ferritin Synthesis and Secretion

Ferritin synthesis is regulated by intracellular nonheme iron levels, governed mainly by an iron response element (IRE) and iron response protein (IRP) translational repression system. Both FTH and FTL messenger RNA (mRNA) contain an IRE that is a regulatory stem-loop structure in the 5´ untranslated region. When the IRE is bound by IRP1 or IRP2, mRNA translation of ferritin subunits is suppressed.⁶ In low iron conditions, IRPs have greater affinity for IRE, and binding suppresses ferritin translation.¹² In high iron conditions, IRPs have a decreased affinity for IRE, and ferritin mRNA synthesis is increased.¹³ Additionally, inflammatory cytokines such as tumor necrosis factor α and IL-1α transcriptionally induce FTH synthesis, resulting in an increased population of H-rich ferritins.^11,14-16 A study using cultured human primary skin fibroblasts demonstrated UV radiation–induced increases in free intracellular iron content.^17,18 Pourzand et al¹⁸ suggested that UV-mediated damage of lysosomal membranes results in leakage of lysosomal proteases into the cytosol, contributing to degradation of intracellular ferritin and subsequent release of iron within skin fibroblasts. The increased intracellular iron downregulates IRPs and increases ferritin mRNA synthesis,¹⁸ consistent with prior findings of increased ferritin synthesis in skin that is induced by UV radiation.¹⁹

Molecular analysis of serum ferritin in iron-overloaded mice revealed that extracellular ferritin found in the serum is composed of a greater fraction of FTL and has lower iron content than intracellular ferritin. The low iron content of serum ferritin compared with intracellular ferritin and transferrin suggests that serum ferritin is not a major pathway of systemic iron transport.¹⁰ However, locally secreted ferritins may play a greater role in iron transport and release in selected tissues. Additionally, in vitro studies of cell cultures from humans and mice have demonstrated the ability of macrophages to secrete ferritin, suggesting that macrophages are an important cellular source of serum ferritin.^10,20 As such, serum ferritin generally may reflect body iron status but more specifically reflects macrophage iron status.¹⁰ Although the exact pathways of ferritin release are unknown, it is hypothesized that ferritin secretion occurs through cytosolic autophagy followed by secretion of proteins from the lysosomal compartment.^10,18,21

Low Ferritin and Iron Deficiency—Although bone marrow biopsy with iron staining remains the gold standard for diagnosis of iron deficiency, serum ferritin is a much more accessible and less invasive tool for evaluation of iron status. A serum ferritin level below 12 μg/L is highly specific for iron depletion,²² with a higher cutoff recommended in clinical practice to improve diagnostic sensitivity.^23,24 Conditions independent of iron deficiency that may reduce serum ferritin include hypothyroidism and ascorbate deficiency, though neither condition has been reported to interfere with appropriate diagnosis of iron deficiency.²⁵ Guyatt et al²⁶ conducted a systematic review of laboratory tests used in the diagnosis of iron deficiency anemia and identified 55 studies suitable for inclusion. Based on an area under the receiver operating characteristic curve (AUROC) of 0.95, serum ferritin values were superior to transferrin saturation (AUROC, 0.74), red cell protoporphyrin (AUROC, 0.77), red cell volume distribution width (AUROC, 0.62), and mean cell volume (AUROC, 0.76) for diagnosis of IDA, verified by histologic examination of aspirated bone marrow.²⁶ The likelihood ratio of iron deficiency begins to decrease for serum ferritin values of 40 μg/L or greater. For patients with inflammatory conditions—patients with concomitant chronic renal failure, inflammatory disease, infection, rheumatoid arthritis, liver disease, inflammatory bowel disease, and malignancy—the likelihood of iron deficiency begins to decrease at serum ferritin levels of 70 μg/L or greater.²⁶ Similarly, the World Health Organization recommends that in adults with infection or inflammation, serum ferritin levels lower than 70 μg/L may be used to indicate iron deficiency.²⁴ A serum ferritin level of 41 μg/L or lower was found to have a sensitivity and specificity of 98% for discriminating between iron-deficiency anemia and anemia of chronic disease (diagnosed based on bone marrow biopsy with iron staining), with an AUROC of 0.98.²⁷ As such, we recommend using a serum ferritin level of 40 μg/L or lower in patients who are otherwise healthy as an indicator of iron deficiency.

The threshold for iron supplementation may vary based on age, sex, and race. In women, ferritin levels increase during menopause and peak after menopause; ferritin levels are higher in men than in women.^28-30 A multisite longitudinal cohort study of 70 women in the United States found that the mean (SD) ferritin valuewas 69.5 (81.7) μg/L premenopause and 128.8 (125.7) μg/L postmenopause (P<.01).³¹ A separate longitudinal survey study of 8564 patients in China found that the mean (SE) ferritin value was 201.55 (3.60) μg/L for men and 80.46 (1.64) μg/L for women (P<.0001).³² Analysis of serum ferritin levels of 3554 male patients from the third National Health and Nutrition Examination Survey demonstrated that patients who self-reported as non-Hispanic Black (n=1616) had significantly higher serum ferritin levels than non-Hispanic White patients (n=1938)(serum ferritin difference of 37.1 μg/L)(P<.0001).³³ The British Society for Haematology guidelines recommend that the threshold of serum ferritin for diagnosing iron deficiency should take into account age-, sex-, and race-based differences.³⁴ Ferritin and Hair—Cutaneous manifestations of iron deficiency include koilonychia, glossitis, pruritus, angular cheilitis, and telogen effluvium (TE).¹ A case-control study of 30 females aged 15 to 45 years demonstrated that the mean (SD) ferritin level was significantly lower in patients with TE than those with no hair loss (16.3 [12.6] ng/mL vs 60.3 [50.1] ng/mL; P<.0001). Using a threshold of 30 μg/L or lower, the investigators found that the odds ratio for TE was 21.0 (95% CI, 4.2-105.0) in patients with low serum ferritin.³⁵

Another retrospective review of 54 patients with diffuse hair loss and 55 controls compared serum vitamin B₁₂, folate, thyroid-stimulating hormone, zinc, ferritin, and 25-hydroxy vitamin D levels between the 2 groups.³⁶ Exclusion criteria were clinical diagnoses of female pattern hair loss (androgenetic alopecia), pregnancy, menopause, metabolic and endocrine disorders, hormone replacement therapy, chemotherapy, immunosuppressive therapy, vitamin and mineral supplementation, scarring alopecia, eating disorders, and restrictive diets. Compared with controls, patients with diffuse nonscarring hair loss were found to have significantly lower ferritin (mean [SD], 14.72 [10.70] ng/mL vs 25.30 [14.41] ng/mL; P<.001) and 25-hydroxy vitamin D levels (mean [SD], 14.03 [8.09] ng/mL vs 17.01 [8.59] ng/mL; P=.01).³⁶

In contrast, a separate case-control study of 381 cases and 76 controls found no increase in the rate of iron deficiency—defined as ferritin ≤15 μg/L or ≤40 μg/L—among women with female pattern hair loss or chronic TE vs controls.³⁷ Taken together, these studies suggest that iron status may play a role in TE, a process that may result from nutritional deficiency, trauma, or physical or psychological stress³⁸; however, there is insufficient evidence to suggest that low iron status impacts androgenetic alopecia, in which its multifactorial pathogenesis implicates genetic and hormonal factors.³⁹ More research is needed to clarify the potential associations between iron deficiency and types of hair loss. Additionally, it is unclear whether iron supplementation improves hair growth parameters such as density and caliber.⁴⁰

Low serum ferritin (<40 μg/L) with concurrent symptoms of iron deficiency, including fatigue, pallor, dyspnea on exertion, or hair loss, should prompt treatment with supplemental iron.^41-43 Generally, ferrous (Fe2⁺) salts are preferred to ferric (Fe3⁺) salts, as the former is more readily absorbed through the duodenal mucosa⁴⁴ and is the more common formulation in commercially available supplements in the United States.⁴⁵ Oral supplementation with ferrous sulfate 325 mg (65 mg elemental iron) tablets is the first-line therapy for iron deficiency anemia.¹ Alternatively, ferrous gluconate 324 mg (38 mg elemental iron) over-the-counter and its liquid form has demonstrated superior absorption compared to ferrous sulfate tablets in a clinical study with peritoneal dialysis patients.^1,46 One study suggested that oral iron 40 to 80 mg should be taken every other day to increase absorption.⁴⁷ Due to improved bioavailability, intravenous iron may be utilized in patients with malabsorption, renal failure, or intolerance to oral iron (including those with gastric ulcers or active inflammatory bowel disease), with the formulation chosen based on underlying comorbidities and potential risks.^1,48 The theoretical risk for potentiating bacterial growth by increasing the amount of unbound iron in the blood raises concerns of iron supplementation in patients with infection or sepsis. Although far from definitive, existing data suggest that risk for infection is greater with intravenous iron supplementation and should be carefully considered prior to use.^49,50Elevated Ferritin—Elevated ferritin may be difficult to interpret given the multitude of conditions that can cause it.^23,51,52 Elevated serum ferritin can be broadly characterized by increased synthesis due to iron overload, increased synthesis due to inflammation, or increased ferritin release from cellular damage.³⁴ Further complicating interpretation is the potential diurnal fluctuations in serum iron levels dependent on dietary intake and timing of laboratory evaluation, choice of assay, differences in reference standards, and variations in calibration procedures that can lead to analytic variability in the measurement of ferritin.^23,53,54

Among healthy patients, serum ferritin is directly proportional to iron status.^9,51 A study utilizing weekly phlebotomy of 22 healthy participants to measure serum ferritin and calculate mobilizable storage iron found a strong positive correlation between the 2 variables (r=0.83, P<.001), with each 1-μg/L increase of serum ferritin corresponding to approximately an 8-mg increase of storage iron; the initial serum ferritin values ranged from 2 to 83 μg/L in females and 36 to 224 μg/L in males.⁵⁵ The correlation of ferritin with iron status also was supported by the significant correlation between the number of transfusions received in patients with transfusion-related iron overload and serum ferritin levels (r=0.89, P<.001), with an average increase of 60 μg/L per transfusion.⁵¹

Clinical guidelines on the interpretation of serum ferritin levels by Cullis et al³⁴ recommend a normal upper limit of 200 μg/L for healthy females and 300 μg/L for healthy males. Outside of clinical syndromes associated with iron overload, Lee and Means⁵⁶ found that serum ferritin of 1000 μg/L or higher was a nonspecific marker of disease, including infection and/or neoplastic disorders. We have adapted these guidelines to propose a workflow for evaluation of serum ferritin levels (Figure). In patients with inflammatory conditions or those affected by metabolic syndrome, elevated serum ferritin does not correlate with body iron status.^57,58 It is believed that inflammatory cytokines, including tumor necrosis factor α and IL-1α, can upregulate ferritin synthesis independent of cellular iron stores.^15,16 Several studies have examined the relationship between insulin resistance and/or metabolic syndrome with serum ferritin levels.^31,32 Han et al³² found that elevated serum ferritin was significantly associated with higher risk for metabolic syndrome in men (P<.0001) but not in women.

Although cutaneous manifestations of iron overload can be seen as skin hyperpigmentation due to increased iron deposits and increased melanin production,²² the effects of elevated ferritin on the skin and hair are not well known. Iron overload is a known trigger of porphyria cutanea tarda (PCT),⁵⁹ a condition in which reduced or absent enzymatic activity of uroporphyrinogen decarboxylase (UROD) leads to build up of toxic porphyrins in various organs.⁶⁰ In the skin, PCT manifests as a blistering photosensitive eruption that may resolve as dyspigmentation, scarring, and milia.⁶¹ Phlebotomy is first-line therapy in PCT to reduce serum iron and subsequent formation of UROD inhibitors, with guidelines suggesting discontinuation of phlebotomy when serum ferritin levels reach 20 ng/mL or lower.⁶⁰ Hyperferritinemia (serum ferritin >500 μg/L) is a common finding in several inflammatory disorders often accompanied by clinically apparent cutaneous symptoms such as adult-onset Still disease,⁶² hemophagocytic lymphohistiocytosis,^63,64 and anti-melanoma differentiation-associated gene 5 dermatomyositis.⁶⁵ Among these conditions, serum ferritin levels have been reported to correlate with disease activity, raising the question of whether ferritin is a bystander or a driver of the underlying pathology.^62,66,67 However, rapid decline of serum ferritin levels with treatment and control of inflammatory cytokines suggest that ferritin is unlikely to contribute to pathology.^62,67

Final Thoughts

Many clinical studies have examined the association between hair health and body iron status, the collective findings of which suggest that iron deficiency may be associated with TE. Among commonly measured serum iron parameters, low ferritin is a highly specific and sensitive marker for diagnosing iron deficiency. Serum ferritin may be a clinically useful tool for ruling out underlying iron deficiency in patients presenting with hair loss. Despite advances in our understanding of the molecular mechanisms of ferritin synthesis and regulation, whether ferritin itself contributes to cutaneous pathology is poorly understood.^35,36,68-74 For patients who are otherwise healthy with low suspicion for inflammatory disorders, chronic systemic illnesses, or malignancy, serum ferritin can be used as an indicator of body iron status. The workup for slightly elevated serum ferritin should be interpreted in the context of other laboratory findings and should be reassessed over time. Serum ferritin levels above 1000 μg/L warrant further investigation into causes such as iron overload conditions and underlying inflammatory conditions or malignancy.

Nail surgical procedures including biopsies, correction of onychocryptosis and other deformities, and excision of tumors are essential for diagnosing and treating nail disorders. Nail surgery often is perceived by dermatologists as a difficult-to-perform, high-risk procedure associated with patient anxiety, pain, and permanent scarring, which may limit implementation. Misconceptions about nail surgical techniques, aftercare, and patient outcomes are prevalent, and a paucity of nail surgery randomized clinical trials hinder formulation of standardized guidelines.¹ In a survey-based study of 95 dermatology residency programs (240 total respondents), 58% of residents said they performed 10 or fewer nail procedures, 10% performed more than 10 procedures, 25% only observed nail procedures, 4% were exposed by lecture only, and 1% had no exposure; 30% said they felt incompetent performing nail biopsies.² In a retrospective study of nail biopsies performed from 2012 to 2017 in the Medicare Provider Utilization and Payment Database, only 0.28% and 1.01% of all general dermatologists and Mohs surgeons, respectively, performed nail biopsies annually.³ A minimally invasive nail surgery technique is essential to alleviating dermatologist and patient apprehension, which may lead to greater adoption and improved outcomes.

Reduce Patient Anxiety During Nail Surgery

The prospect of undergoing nail surgery can be psychologically distressing to patients because the nail unit is highly sensitive, intraoperative and postoperative pain are common concerns, patient education materials generally are scarce and inaccurate,⁴ and procedures are performed under local anesthesia with the patient fully awake. In a prospective study of 48 patients undergoing nail surgery, the median preoperative Spielberger State-Trait Anxiety Inventory level was 42.00 (IQR, 6.50).⁵ Patient distress may be minimized by providing verbal and written educational materials, discussing expectations, and preoperatively using fast-acting benzodiazepines when necessary.⁶ Utilizing a sleep mask,⁷ stress ball,⁸ music,⁹ and/or virtual reality¹⁰ also may reduce patient anxiety during nail surgery.

Use Proper Anesthetic Techniques

Proper anesthetic technique is crucial to achieve the optimal patient experience during nail surgery. With a wing block, the anesthetic is injected into 3 points: (1) the proximal nail fold, (2) the medial/lateral fold, and (3) the hyponychium. The wing block is the preferred technique by many nail surgeons because the second and third injections are given in skin that is already anesthetized, reducing patient discomfort to a single pinprick¹¹; additionally, there is lower postoperative paresthesia risk with the wing block compared with other digital nerve blocks.¹² Ropivacaine, a fast-acting and long-acting anesthetic, is preferred over lidocaine to minimize immediate postoperative pain. Buffering the anesthetic solution to physiologic pH and slow infiltration can reduce pain during infiltration.¹² Distraction¹² provided by ethyl chloride refrigerant spray, an air-cooling device,¹³ or vibration also can reduce pain during anesthesia.

Punch Biopsy and Excision Tips

The punch biopsy is a minimally invasive method for diagnosing various neoplastic and inflammatory nail unit conditions, except for pigmented lesions.¹² For polydactylous nail conditions requiring biopsy, a digit on the nondominant hand should be selected if possible. The punch is applied directly to the nail plate and twisted with downward pressure until the bone is reached, with the instrument withdrawn slowly to prevent surrounding nail plate detachment. Hemostasis is easily achieved with direct pressure and/or use of epinephrine or ropivacaine during anesthesia, and a digital tourniquet generally is not required. Applying microporous polysaccharide hemospheres powder¹⁴ or kaolin-impregnated gauze¹⁵ with direct pressure is helpful in managing continued bleeding following nail surgery. Punching through the proximal nail matrix should be avoided to prevent permanent onychodystrophy.

A tangential matrix shave biopsy requires a more practiced technique and is preferred for sampling longitudinal melanonychia. A partial proximal nail plate avulsion adequately exposes the origin of pigment and avoids complete avulsion, which may cause more onychodystrophy.¹⁶ For broad erythronychia, a total nail avulsion may be necessary. For narrow, well-defined erythronychia, a less-invasive approach such as trap-door avulsion, longitudinal nail strip, or lateral nail plate curl, depending on the etiology, often is sufficient. Tissue excision should be tailored to the specific etiology, with localized excision sufficient for glomus tumors; onychopapillomas require tangential excision of the distal matrix, entire nail bed, and hyperkeratotic papule at the hyponychium. Pushing the cuticle with an elevator/spatula instead of making 2 tangential incisions on the proximal nail fold has been suggested to decrease postoperative paronychia risk.¹² A Teflon-coated blade is used to achieve a smooth cut with minimal drag, enabling collection of specimens less than 1 mm thick, which provides sufficient nail matrix epithelium and dermis for histologic examination.¹⁶ After obtaining the specimen, the avulsed nail plate may be sutured back to the nail bed using a rapidly absorbable suture such as polyglactin 910, serving as a temporary biological dressing and splint for the nail unit during healing.¹² In a retrospective study of 30 patients with longitudinal melanonychia undergoing tangential matrix excision, 27% (8/30) developed postoperative onychodystrophy.¹⁷ Although this technique carries relatively lower risk of permanent onychodystrophy compared to other methods, it still is important to acknowledge during the preoperative consent process.¹²

The lateral longitudinal excision is a valuable technique for diagnosing nail unit inflammatory conditions. Classically, a longitudinal sample including the proximal nail fold, complete matrix, lateral plate, lateral nail fold, hyponychium, and distal tip skin is obtained, with a 10% narrowing of the nail plate expected. If the lateral horn of the nail matrix is missed, permanent lateral malalignment and spicule formation are potential risks. To minimize narrowing of the nail plate and postoperative paronychia, a longitudinal nail strip—where the proximal nail fold and matrix are left intact—is an alternative technique.¹⁸

Pain Management Approaches

Appropriate postoperative pain management is crucial for optimizing patient outcomes. In a prospective study of 20 patients undergoing nail biopsy, the mean pain score 6 to 12 hours postprocedure was 5.7 on a scale of 0 to 10. Patients with presurgery pain vs those without experienced significantly higher pain levels both during anesthesia and after surgery (both P<.05).¹⁹ Therefore, a personalized approach to pain management based on presence of presurgical pain is warranted. In a randomized clinical trial of 16 patients anesthetized with lidocaine 2% and intraoperative infiltration with a combination of ropivacaine 0.5 mL and triamcinolone (10 mg/mL [0.5 mL]) vs lidocaine 2% alone, the intraoperative mixture reduced postoperative pain (mean pain score, 2 of 10 at 48 hours postprocedure vs 7.88 of 10 in the control group [P<.001]).²⁰

A Cochrane review of 4 unpublished dental and orthopedic surgery studies showed that gabapentin is superior to placebo in the treatment of acute postoperative pain. Therefore, a single dose of gabapentin (250 mg) may be considered in patients at risk for high postoperative pain.²¹ In a randomized double-blind trial of 210 Mohs micrographic surgery patients, those receiving acetaminophen and ibuprofen reported lower pain scores at 2, 4, 8, and 12 hours postprocedure compared with patients taking acetaminophen and codeine or acetaminophen alone.²² However, the role of opioids in pain management following nail surgery has not been adequately studied.

Wound Care

An efficient dressing protects the surgical wound, facilitates healing, and provides comfort. In our experience, an initial layer of petrolatum-impregnated gauze followed by a pressure-padded bandage consisting of folded dry gauze secured in place with longitudinally applied tape to avoid a tourniquet effect is effective for nail surgical wounds. As the last step, self-adherent elastic wrap is applied around the digit and extended proximally to prevent a tourniquet effect.²³

Final Thoughts

Due to the intricate anatomy of the nail unit, nail surgeries are inherently more invasive than most dermatologic surgical procedures. It is crucial to adopt a minimally invasive approach to reduce tissue damage and potential complications in both the short-term and long-term. Adopting this approach may substantially improve patient outcomes and enhance diagnostic and treatment efficacy.

Nail surgical procedures including biopsies, correction of onychocryptosis and other deformities, and excision of tumors are essential for diagnosing and treating nail disorders. Nail surgery often is perceived by dermatologists as a difficult-to-perform, high-risk procedure associated with patient anxiety, pain, and permanent scarring, which may limit implementation. Misconceptions about nail surgical techniques, aftercare, and patient outcomes are prevalent, and a paucity of nail surgery randomized clinical trials hinder formulation of standardized guidelines.¹ In a survey-based study of 95 dermatology residency programs (240 total respondents), 58% of residents said they performed 10 or fewer nail procedures, 10% performed more than 10 procedures, 25% only observed nail procedures, 4% were exposed by lecture only, and 1% had no exposure; 30% said they felt incompetent performing nail biopsies.² In a retrospective study of nail biopsies performed from 2012 to 2017 in the Medicare Provider Utilization and Payment Database, only 0.28% and 1.01% of all general dermatologists and Mohs surgeons, respectively, performed nail biopsies annually.³ A minimally invasive nail surgery technique is essential to alleviating dermatologist and patient apprehension, which may lead to greater adoption and improved outcomes.

Reduce Patient Anxiety During Nail Surgery

The prospect of undergoing nail surgery can be psychologically distressing to patients because the nail unit is highly sensitive, intraoperative and postoperative pain are common concerns, patient education materials generally are scarce and inaccurate,⁴ and procedures are performed under local anesthesia with the patient fully awake. In a prospective study of 48 patients undergoing nail surgery, the median preoperative Spielberger State-Trait Anxiety Inventory level was 42.00 (IQR, 6.50).⁵ Patient distress may be minimized by providing verbal and written educational materials, discussing expectations, and preoperatively using fast-acting benzodiazepines when necessary.⁶ Utilizing a sleep mask,⁷ stress ball,⁸ music,⁹ and/or virtual reality¹⁰ also may reduce patient anxiety during nail surgery.

Use Proper Anesthetic Techniques

Proper anesthetic technique is crucial to achieve the optimal patient experience during nail surgery. With a wing block, the anesthetic is injected into 3 points: (1) the proximal nail fold, (2) the medial/lateral fold, and (3) the hyponychium. The wing block is the preferred technique by many nail surgeons because the second and third injections are given in skin that is already anesthetized, reducing patient discomfort to a single pinprick¹¹; additionally, there is lower postoperative paresthesia risk with the wing block compared with other digital nerve blocks.¹² Ropivacaine, a fast-acting and long-acting anesthetic, is preferred over lidocaine to minimize immediate postoperative pain. Buffering the anesthetic solution to physiologic pH and slow infiltration can reduce pain during infiltration.¹² Distraction¹² provided by ethyl chloride refrigerant spray, an air-cooling device,¹³ or vibration also can reduce pain during anesthesia.

Punch Biopsy and Excision Tips

The punch biopsy is a minimally invasive method for diagnosing various neoplastic and inflammatory nail unit conditions, except for pigmented lesions.¹² For polydactylous nail conditions requiring biopsy, a digit on the nondominant hand should be selected if possible. The punch is applied directly to the nail plate and twisted with downward pressure until the bone is reached, with the instrument withdrawn slowly to prevent surrounding nail plate detachment. Hemostasis is easily achieved with direct pressure and/or use of epinephrine or ropivacaine during anesthesia, and a digital tourniquet generally is not required. Applying microporous polysaccharide hemospheres powder¹⁴ or kaolin-impregnated gauze¹⁵ with direct pressure is helpful in managing continued bleeding following nail surgery. Punching through the proximal nail matrix should be avoided to prevent permanent onychodystrophy.

A tangential matrix shave biopsy requires a more practiced technique and is preferred for sampling longitudinal melanonychia. A partial proximal nail plate avulsion adequately exposes the origin of pigment and avoids complete avulsion, which may cause more onychodystrophy.¹⁶ For broad erythronychia, a total nail avulsion may be necessary. For narrow, well-defined erythronychia, a less-invasive approach such as trap-door avulsion, longitudinal nail strip, or lateral nail plate curl, depending on the etiology, often is sufficient. Tissue excision should be tailored to the specific etiology, with localized excision sufficient for glomus tumors; onychopapillomas require tangential excision of the distal matrix, entire nail bed, and hyperkeratotic papule at the hyponychium. Pushing the cuticle with an elevator/spatula instead of making 2 tangential incisions on the proximal nail fold has been suggested to decrease postoperative paronychia risk.¹² A Teflon-coated blade is used to achieve a smooth cut with minimal drag, enabling collection of specimens less than 1 mm thick, which provides sufficient nail matrix epithelium and dermis for histologic examination.¹⁶ After obtaining the specimen, the avulsed nail plate may be sutured back to the nail bed using a rapidly absorbable suture such as polyglactin 910, serving as a temporary biological dressing and splint for the nail unit during healing.¹² In a retrospective study of 30 patients with longitudinal melanonychia undergoing tangential matrix excision, 27% (8/30) developed postoperative onychodystrophy.¹⁷ Although this technique carries relatively lower risk of permanent onychodystrophy compared to other methods, it still is important to acknowledge during the preoperative consent process.¹²

The lateral longitudinal excision is a valuable technique for diagnosing nail unit inflammatory conditions. Classically, a longitudinal sample including the proximal nail fold, complete matrix, lateral plate, lateral nail fold, hyponychium, and distal tip skin is obtained, with a 10% narrowing of the nail plate expected. If the lateral horn of the nail matrix is missed, permanent lateral malalignment and spicule formation are potential risks. To minimize narrowing of the nail plate and postoperative paronychia, a longitudinal nail strip—where the proximal nail fold and matrix are left intact—is an alternative technique.¹⁸

Pain Management Approaches

Appropriate postoperative pain management is crucial for optimizing patient outcomes. In a prospective study of 20 patients undergoing nail biopsy, the mean pain score 6 to 12 hours postprocedure was 5.7 on a scale of 0 to 10. Patients with presurgery pain vs those without experienced significantly higher pain levels both during anesthesia and after surgery (both P<.05).¹⁹ Therefore, a personalized approach to pain management based on presence of presurgical pain is warranted. In a randomized clinical trial of 16 patients anesthetized with lidocaine 2% and intraoperative infiltration with a combination of ropivacaine 0.5 mL and triamcinolone (10 mg/mL [0.5 mL]) vs lidocaine 2% alone, the intraoperative mixture reduced postoperative pain (mean pain score, 2 of 10 at 48 hours postprocedure vs 7.88 of 10 in the control group [P<.001]).²⁰

A Cochrane review of 4 unpublished dental and orthopedic surgery studies showed that gabapentin is superior to placebo in the treatment of acute postoperative pain. Therefore, a single dose of gabapentin (250 mg) may be considered in patients at risk for high postoperative pain.²¹ In a randomized double-blind trial of 210 Mohs micrographic surgery patients, those receiving acetaminophen and ibuprofen reported lower pain scores at 2, 4, 8, and 12 hours postprocedure compared with patients taking acetaminophen and codeine or acetaminophen alone.²² However, the role of opioids in pain management following nail surgery has not been adequately studied.

Wound Care

An efficient dressing protects the surgical wound, facilitates healing, and provides comfort. In our experience, an initial layer of petrolatum-impregnated gauze followed by a pressure-padded bandage consisting of folded dry gauze secured in place with longitudinally applied tape to avoid a tourniquet effect is effective for nail surgical wounds. As the last step, self-adherent elastic wrap is applied around the digit and extended proximally to prevent a tourniquet effect.²³

Final Thoughts

Due to the intricate anatomy of the nail unit, nail surgeries are inherently more invasive than most dermatologic surgical procedures. It is crucial to adopt a minimally invasive approach to reduce tissue damage and potential complications in both the short-term and long-term. Adopting this approach may substantially improve patient outcomes and enhance diagnostic and treatment efficacy.

Nail surgical procedures including biopsies, correction of onychocryptosis and other deformities, and excision of tumors are essential for diagnosing and treating nail disorders. Nail surgery often is perceived by dermatologists as a difficult-to-perform, high-risk procedure associated with patient anxiety, pain, and permanent scarring, which may limit implementation. Misconceptions about nail surgical techniques, aftercare, and patient outcomes are prevalent, and a paucity of nail surgery randomized clinical trials hinder formulation of standardized guidelines.¹ In a survey-based study of 95 dermatology residency programs (240 total respondents), 58% of residents said they performed 10 or fewer nail procedures, 10% performed more than 10 procedures, 25% only observed nail procedures, 4% were exposed by lecture only, and 1% had no exposure; 30% said they felt incompetent performing nail biopsies.² In a retrospective study of nail biopsies performed from 2012 to 2017 in the Medicare Provider Utilization and Payment Database, only 0.28% and 1.01% of all general dermatologists and Mohs surgeons, respectively, performed nail biopsies annually.³ A minimally invasive nail surgery technique is essential to alleviating dermatologist and patient apprehension, which may lead to greater adoption and improved outcomes.

Reduce Patient Anxiety During Nail Surgery

The prospect of undergoing nail surgery can be psychologically distressing to patients because the nail unit is highly sensitive, intraoperative and postoperative pain are common concerns, patient education materials generally are scarce and inaccurate,⁴ and procedures are performed under local anesthesia with the patient fully awake. In a prospective study of 48 patients undergoing nail surgery, the median preoperative Spielberger State-Trait Anxiety Inventory level was 42.00 (IQR, 6.50).⁵ Patient distress may be minimized by providing verbal and written educational materials, discussing expectations, and preoperatively using fast-acting benzodiazepines when necessary.⁶ Utilizing a sleep mask,⁷ stress ball,⁸ music,⁹ and/or virtual reality¹⁰ also may reduce patient anxiety during nail surgery.

Use Proper Anesthetic Techniques

Proper anesthetic technique is crucial to achieve the optimal patient experience during nail surgery. With a wing block, the anesthetic is injected into 3 points: (1) the proximal nail fold, (2) the medial/lateral fold, and (3) the hyponychium. The wing block is the preferred technique by many nail surgeons because the second and third injections are given in skin that is already anesthetized, reducing patient discomfort to a single pinprick¹¹; additionally, there is lower postoperative paresthesia risk with the wing block compared with other digital nerve blocks.¹² Ropivacaine, a fast-acting and long-acting anesthetic, is preferred over lidocaine to minimize immediate postoperative pain. Buffering the anesthetic solution to physiologic pH and slow infiltration can reduce pain during infiltration.¹² Distraction¹² provided by ethyl chloride refrigerant spray, an air-cooling device,¹³ or vibration also can reduce pain during anesthesia.

Punch Biopsy and Excision Tips

The punch biopsy is a minimally invasive method for diagnosing various neoplastic and inflammatory nail unit conditions, except for pigmented lesions.¹² For polydactylous nail conditions requiring biopsy, a digit on the nondominant hand should be selected if possible. The punch is applied directly to the nail plate and twisted with downward pressure until the bone is reached, with the instrument withdrawn slowly to prevent surrounding nail plate detachment. Hemostasis is easily achieved with direct pressure and/or use of epinephrine or ropivacaine during anesthesia, and a digital tourniquet generally is not required. Applying microporous polysaccharide hemospheres powder¹⁴ or kaolin-impregnated gauze¹⁵ with direct pressure is helpful in managing continued bleeding following nail surgery. Punching through the proximal nail matrix should be avoided to prevent permanent onychodystrophy.

A tangential matrix shave biopsy requires a more practiced technique and is preferred for sampling longitudinal melanonychia. A partial proximal nail plate avulsion adequately exposes the origin of pigment and avoids complete avulsion, which may cause more onychodystrophy.¹⁶ For broad erythronychia, a total nail avulsion may be necessary. For narrow, well-defined erythronychia, a less-invasive approach such as trap-door avulsion, longitudinal nail strip, or lateral nail plate curl, depending on the etiology, often is sufficient. Tissue excision should be tailored to the specific etiology, with localized excision sufficient for glomus tumors; onychopapillomas require tangential excision of the distal matrix, entire nail bed, and hyperkeratotic papule at the hyponychium. Pushing the cuticle with an elevator/spatula instead of making 2 tangential incisions on the proximal nail fold has been suggested to decrease postoperative paronychia risk.¹² A Teflon-coated blade is used to achieve a smooth cut with minimal drag, enabling collection of specimens less than 1 mm thick, which provides sufficient nail matrix epithelium and dermis for histologic examination.¹⁶ After obtaining the specimen, the avulsed nail plate may be sutured back to the nail bed using a rapidly absorbable suture such as polyglactin 910, serving as a temporary biological dressing and splint for the nail unit during healing.¹² In a retrospective study of 30 patients with longitudinal melanonychia undergoing tangential matrix excision, 27% (8/30) developed postoperative onychodystrophy.¹⁷ Although this technique carries relatively lower risk of permanent onychodystrophy compared to other methods, it still is important to acknowledge during the preoperative consent process.¹²

The lateral longitudinal excision is a valuable technique for diagnosing nail unit inflammatory conditions. Classically, a longitudinal sample including the proximal nail fold, complete matrix, lateral plate, lateral nail fold, hyponychium, and distal tip skin is obtained, with a 10% narrowing of the nail plate expected. If the lateral horn of the nail matrix is missed, permanent lateral malalignment and spicule formation are potential risks. To minimize narrowing of the nail plate and postoperative paronychia, a longitudinal nail strip—where the proximal nail fold and matrix are left intact—is an alternative technique.¹⁸

Pain Management Approaches

Appropriate postoperative pain management is crucial for optimizing patient outcomes. In a prospective study of 20 patients undergoing nail biopsy, the mean pain score 6 to 12 hours postprocedure was 5.7 on a scale of 0 to 10. Patients with presurgery pain vs those without experienced significantly higher pain levels both during anesthesia and after surgery (both P<.05).¹⁹ Therefore, a personalized approach to pain management based on presence of presurgical pain is warranted. In a randomized clinical trial of 16 patients anesthetized with lidocaine 2% and intraoperative infiltration with a combination of ropivacaine 0.5 mL and triamcinolone (10 mg/mL [0.5 mL]) vs lidocaine 2% alone, the intraoperative mixture reduced postoperative pain (mean pain score, 2 of 10 at 48 hours postprocedure vs 7.88 of 10 in the control group [P<.001]).²⁰

A Cochrane review of 4 unpublished dental and orthopedic surgery studies showed that gabapentin is superior to placebo in the treatment of acute postoperative pain. Therefore, a single dose of gabapentin (250 mg) may be considered in patients at risk for high postoperative pain.²¹ In a randomized double-blind trial of 210 Mohs micrographic surgery patients, those receiving acetaminophen and ibuprofen reported lower pain scores at 2, 4, 8, and 12 hours postprocedure compared with patients taking acetaminophen and codeine or acetaminophen alone.²² However, the role of opioids in pain management following nail surgery has not been adequately studied.

Wound Care

An efficient dressing protects the surgical wound, facilitates healing, and provides comfort. In our experience, an initial layer of petrolatum-impregnated gauze followed by a pressure-padded bandage consisting of folded dry gauze secured in place with longitudinally applied tape to avoid a tourniquet effect is effective for nail surgical wounds. As the last step, self-adherent elastic wrap is applied around the digit and extended proximally to prevent a tourniquet effect.²³

Final Thoughts

Due to the intricate anatomy of the nail unit, nail surgeries are inherently more invasive than most dermatologic surgical procedures. It is crucial to adopt a minimally invasive approach to reduce tissue damage and potential complications in both the short-term and long-term. Adopting this approach may substantially improve patient outcomes and enhance diagnostic and treatment efficacy.

Deanna Denham Hughes was stunned when she was diagnosed with ovarian cancer in 2022. She was only 32. She had no family history of cancer, and tests found no genetic link. Ms. Hughes wondered why she, an otherwise healthy Black mother of two, would develop a malignancy known as a “silent killer.”

After emergency surgery to remove the mass, along with her ovaries, uterus, fallopian tubes, and appendix, Ms. Hughes said, she saw an Instagram post in which a woman with uterine cancer linked her condition to chemical hair straighteners.

“I almost fell over,” she said from her home in Smyrna, Ga.

When Ms. Hughes was about 4, her mother began applying a chemical straightener, or relaxer, to her hair every 6-8 weeks. “It burned, and it smelled awful,” Ms. Hughes recalled. “But it was just part of our routine to ‘deal with my hair.’ ”

The routine continued until she went to college and met other Black women who wore their hair naturally. Soon, Ms. Hughes quit relaxers.

Social and economic pressures have long compelled Black girls and women to straighten their hair to conform to Eurocentric beauty standards. But chemical straighteners are stinky and costly and sometimes cause painful scalp burns. Mounting evidence now shows they could be a health hazard.

Relaxers can contain carcinogens, such as formaldehyde-releasing agents, phthalates, and other endocrine-disrupting compounds, according to National Institutes of Health studies. The compounds can mimic the body’s hormones and have been linked to breast, uterine, and ovarian cancers, studies show.

African American women’s often frequent and lifelong application of chemical relaxers to their hair and scalp might explain why hormone-related cancers kill disproportionately more Black than White women, say researchers and cancer doctors.

“What’s in these products is harmful,” said Tamarra James-Todd, PhD, an epidemiology professor at Harvard T.H. Chan School of Public Health, Boston, who has studied straightening products for the past 20 years.

She believes manufacturers, policymakers, and physicians should warn consumers that relaxers might cause cancer and other health problems.

But regulators have been slow to act, physicians have been reluctant to take up the cause, and racism continues to dictate fashion standards that make it tough for women to quit relaxers, products so addictive they’re known as “creamy crack.”

Michelle Obama straightened her hair when Barack Obama served as president because she believed Americans were “not ready” to see her in braids, the former first lady said after leaving the White House. The U.S. military still prohibited popular Black hairstyles such as dreadlocks and twists while the nation’s first Black president was in office.

California in 2019 became the first of nearly two dozen states to ban race-based hair discrimination. Last year, the U.S. House of Representatives passed similar legislation, known as the CROWN Act, for Creating a Respectful and Open World for Natural Hair. But the bill failed in the Senate.

The need for legislation underscores the challenges Black girls and women face at school and in the workplace.

“You have to pick your struggles,” said Atlanta-based surgical oncologist Ryland J. Gore, MD. She informs her breast cancer patients about the increased cancer risk from relaxers. Despite her knowledge, however, Dr. Gore continues to use chemical straighteners on her own hair, as she has since she was about 7 years old.

“Your hair tells a story,” she said.

In conversations with patients, Dr. Gore sometimes talks about how African American women once wove messages into their braids about the route to take on the Underground Railroad as they sought freedom from slavery.

“It’s just a deep discussion,” one that touches on culture, history, and research into current hairstyling practices, she said. “The data is out there. So patients should be warned, and then they can make a decision.”

The first hint of a connection between hair products and health issues surfaced in the 1990s. Doctors began seeing signs of sexual maturation in Black babies and young girls who developed breasts and pubic hair after using shampoo containing estrogen or placental extract. When the girls stopped using the shampoo, the hair and breast development receded, according to a study published in the journal Clinical Pediatrics in 1998.

Since then, Dr. James-Todd and other researchers have linked chemicals in hair products to a variety of health issues more prevalent among Black women – from early puberty to preterm birth, obesity, and diabetes.

In recent years, researchers have focused on a possible connection between ingredients in chemical relaxers and hormone-related cancers, like the one Ms. Hughes developed, which tend to be more aggressive and deadly in Black women.

A 2017 study found White women who used chemical relaxers were nearly twice as likely to develop breast cancer as those who did not use them. Because the vast majority of the Black study participants used relaxers, researchers could not effectively test the association in Black women, said lead author Adana Llanos, PhD, associate professor of epidemiology at Columbia University’s Mailman School of Public Health, New York.

Researchers did test it in 2020.

The so-called Sister Study, a landmark National Institute of Environmental Health Sciences investigation into the causes of breast cancer and related diseases, followed 50,000 U.S. women whose sisters had been diagnosed with breast cancer and who were cancer-free when they enrolled. Regardless of race, women who reported using relaxers in the prior year were 18% more likely to be diagnosed with breast cancer. Those who used relaxers at least every 5-8 weeks had a 31% higher breast cancer risk.

Nearly 75% of the Black sisters used relaxers in the prior year, compared with 3% of the non-Hispanic White sisters. Three-quarters of Black women self-reported using the straighteners as adolescents, and frequent use of chemical straighteners during adolescence raised the risk of premenopausal breast cancer, a 2021 NIH-funded study in the International Journal of Cancer found.

Another 2021 analysis of the Sister Study data showed sisters who self-reported that they frequently used relaxers or pressing products doubled their ovarian cancer risk. In 2022, another study found frequent use more than doubled uterine cancer risk.

After researchers discovered the link with uterine cancer, some called for policy changes and other measures to reduce exposure to chemical relaxers.

“It is time to intervene,” Dr. Llanos and her colleagues wrote in a Journal of the National Cancer Institute editorial accompanying the uterine cancer analysis. While acknowledging the need for more research, they issued a “call for action.”

No one can say that using permanent hair straighteners will give you cancer, Dr. Llanos said in an interview. “That’s not how cancer works,” she said, noting that some smokers never develop lung cancer, despite tobacco use being a known risk factor.

The body of research linking hair straighteners and cancer is more limited, said Dr. Llanos, who quit using chemical relaxers 15 years ago. But, she asked rhetorically, “Do we need to do the research for 50 more years to know that chemical relaxers are harmful?”

Charlotte R. Gamble, MD, a gynecological oncologist whose Washington, D.C., practice includes Black women with uterine and ovarian cancer, said she and her colleagues see the uterine cancer study findings as worthy of further exploration – but not yet worthy of discussion with patients.

“The jury’s out for me personally,” she said. “There’s so much more data that’s needed.”

Meanwhile, Dr. James-Todd and other researchers believe they have built a solid body of evidence.

“There are enough things we do know to begin taking action, developing interventions, providing useful information to clinicians and patients and the general public,” said Traci N. Bethea, PhD, assistant professor in the Office of Minority Health and Health Disparities Research at Georgetown University.

Responsibility for regulating personal-care products, including chemical hair straighteners and hair dyes – which also have been linked to hormone-related cancers – lies with the Food and Drug Administration. But the FDA does not subject personal-care products to the same approval process it uses for food and drugs. The FDA restricts only 11 categories of chemicals used in cosmetics, while concerns about health effects have prompted the European Union to restrict the use of at least 2,400 substances.

In March, Reps. Ayanna Pressley (D-Mass.) and Shontel Brown (D-Ohio) asked the FDA to investigate the potential health threat posed by chemical relaxers. An FDA representative said the agency would look into it.

Natural hairstyles are enjoying a resurgence among Black girls and women, but many continue to rely on the creamy crack, said Dede Teteh, DrPH, assistant professor of public health at Chapman University, Irvine, Calif.

She had her first straightening perm at 8 and has struggled to withdraw from relaxers as an adult, said Dr. Teteh, who now wears locs. Not long ago, she considered chemically straightening her hair for an academic job interview because she didn’t want her hair to “be a hindrance” when she appeared before White professors.

Dr. Teteh led “The Cost of Beauty,” a hair-health research project published in 2017. She and her team interviewed 91 Black women in Southern California. Some became “combative” at the idea of quitting relaxers and claimed “everything can cause cancer.”

Their reactions speak to the challenges Black women face in America, Dr. Teteh said.

“It’s not that people do not want to hear the information related to their health,” she said. “But they want people to share the information in a way that it’s really empathetic to the plight of being Black here in the United States.”
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

Deanna Denham Hughes was stunned when she was diagnosed with ovarian cancer in 2022. She was only 32. She had no family history of cancer, and tests found no genetic link. Ms. Hughes wondered why she, an otherwise healthy Black mother of two, would develop a malignancy known as a “silent killer.”

After emergency surgery to remove the mass, along with her ovaries, uterus, fallopian tubes, and appendix, Ms. Hughes said, she saw an Instagram post in which a woman with uterine cancer linked her condition to chemical hair straighteners.

“I almost fell over,” she said from her home in Smyrna, Ga.

When Ms. Hughes was about 4, her mother began applying a chemical straightener, or relaxer, to her hair every 6-8 weeks. “It burned, and it smelled awful,” Ms. Hughes recalled. “But it was just part of our routine to ‘deal with my hair.’ ”

The routine continued until she went to college and met other Black women who wore their hair naturally. Soon, Ms. Hughes quit relaxers.

Social and economic pressures have long compelled Black girls and women to straighten their hair to conform to Eurocentric beauty standards. But chemical straighteners are stinky and costly and sometimes cause painful scalp burns. Mounting evidence now shows they could be a health hazard.

Relaxers can contain carcinogens, such as formaldehyde-releasing agents, phthalates, and other endocrine-disrupting compounds, according to National Institutes of Health studies. The compounds can mimic the body’s hormones and have been linked to breast, uterine, and ovarian cancers, studies show.

African American women’s often frequent and lifelong application of chemical relaxers to their hair and scalp might explain why hormone-related cancers kill disproportionately more Black than White women, say researchers and cancer doctors.

“What’s in these products is harmful,” said Tamarra James-Todd, PhD, an epidemiology professor at Harvard T.H. Chan School of Public Health, Boston, who has studied straightening products for the past 20 years.

She believes manufacturers, policymakers, and physicians should warn consumers that relaxers might cause cancer and other health problems.

But regulators have been slow to act, physicians have been reluctant to take up the cause, and racism continues to dictate fashion standards that make it tough for women to quit relaxers, products so addictive they’re known as “creamy crack.”

Michelle Obama straightened her hair when Barack Obama served as president because she believed Americans were “not ready” to see her in braids, the former first lady said after leaving the White House. The U.S. military still prohibited popular Black hairstyles such as dreadlocks and twists while the nation’s first Black president was in office.

California in 2019 became the first of nearly two dozen states to ban race-based hair discrimination. Last year, the U.S. House of Representatives passed similar legislation, known as the CROWN Act, for Creating a Respectful and Open World for Natural Hair. But the bill failed in the Senate.

The need for legislation underscores the challenges Black girls and women face at school and in the workplace.

“You have to pick your struggles,” said Atlanta-based surgical oncologist Ryland J. Gore, MD. She informs her breast cancer patients about the increased cancer risk from relaxers. Despite her knowledge, however, Dr. Gore continues to use chemical straighteners on her own hair, as she has since she was about 7 years old.

“Your hair tells a story,” she said.

In conversations with patients, Dr. Gore sometimes talks about how African American women once wove messages into their braids about the route to take on the Underground Railroad as they sought freedom from slavery.

“It’s just a deep discussion,” one that touches on culture, history, and research into current hairstyling practices, she said. “The data is out there. So patients should be warned, and then they can make a decision.”

The first hint of a connection between hair products and health issues surfaced in the 1990s. Doctors began seeing signs of sexual maturation in Black babies and young girls who developed breasts and pubic hair after using shampoo containing estrogen or placental extract. When the girls stopped using the shampoo, the hair and breast development receded, according to a study published in the journal Clinical Pediatrics in 1998.

Since then, Dr. James-Todd and other researchers have linked chemicals in hair products to a variety of health issues more prevalent among Black women – from early puberty to preterm birth, obesity, and diabetes.

In recent years, researchers have focused on a possible connection between ingredients in chemical relaxers and hormone-related cancers, like the one Ms. Hughes developed, which tend to be more aggressive and deadly in Black women.

A 2017 study found White women who used chemical relaxers were nearly twice as likely to develop breast cancer as those who did not use them. Because the vast majority of the Black study participants used relaxers, researchers could not effectively test the association in Black women, said lead author Adana Llanos, PhD, associate professor of epidemiology at Columbia University’s Mailman School of Public Health, New York.

Researchers did test it in 2020.

The so-called Sister Study, a landmark National Institute of Environmental Health Sciences investigation into the causes of breast cancer and related diseases, followed 50,000 U.S. women whose sisters had been diagnosed with breast cancer and who were cancer-free when they enrolled. Regardless of race, women who reported using relaxers in the prior year were 18% more likely to be diagnosed with breast cancer. Those who used relaxers at least every 5-8 weeks had a 31% higher breast cancer risk.

Nearly 75% of the Black sisters used relaxers in the prior year, compared with 3% of the non-Hispanic White sisters. Three-quarters of Black women self-reported using the straighteners as adolescents, and frequent use of chemical straighteners during adolescence raised the risk of premenopausal breast cancer, a 2021 NIH-funded study in the International Journal of Cancer found.

Another 2021 analysis of the Sister Study data showed sisters who self-reported that they frequently used relaxers or pressing products doubled their ovarian cancer risk. In 2022, another study found frequent use more than doubled uterine cancer risk.

After researchers discovered the link with uterine cancer, some called for policy changes and other measures to reduce exposure to chemical relaxers.

“It is time to intervene,” Dr. Llanos and her colleagues wrote in a Journal of the National Cancer Institute editorial accompanying the uterine cancer analysis. While acknowledging the need for more research, they issued a “call for action.”

No one can say that using permanent hair straighteners will give you cancer, Dr. Llanos said in an interview. “That’s not how cancer works,” she said, noting that some smokers never develop lung cancer, despite tobacco use being a known risk factor.

The body of research linking hair straighteners and cancer is more limited, said Dr. Llanos, who quit using chemical relaxers 15 years ago. But, she asked rhetorically, “Do we need to do the research for 50 more years to know that chemical relaxers are harmful?”

Charlotte R. Gamble, MD, a gynecological oncologist whose Washington, D.C., practice includes Black women with uterine and ovarian cancer, said she and her colleagues see the uterine cancer study findings as worthy of further exploration – but not yet worthy of discussion with patients.

“The jury’s out for me personally,” she said. “There’s so much more data that’s needed.”

Meanwhile, Dr. James-Todd and other researchers believe they have built a solid body of evidence.

“There are enough things we do know to begin taking action, developing interventions, providing useful information to clinicians and patients and the general public,” said Traci N. Bethea, PhD, assistant professor in the Office of Minority Health and Health Disparities Research at Georgetown University.

Responsibility for regulating personal-care products, including chemical hair straighteners and hair dyes – which also have been linked to hormone-related cancers – lies with the Food and Drug Administration. But the FDA does not subject personal-care products to the same approval process it uses for food and drugs. The FDA restricts only 11 categories of chemicals used in cosmetics, while concerns about health effects have prompted the European Union to restrict the use of at least 2,400 substances.

In March, Reps. Ayanna Pressley (D-Mass.) and Shontel Brown (D-Ohio) asked the FDA to investigate the potential health threat posed by chemical relaxers. An FDA representative said the agency would look into it.

Natural hairstyles are enjoying a resurgence among Black girls and women, but many continue to rely on the creamy crack, said Dede Teteh, DrPH, assistant professor of public health at Chapman University, Irvine, Calif.

She had her first straightening perm at 8 and has struggled to withdraw from relaxers as an adult, said Dr. Teteh, who now wears locs. Not long ago, she considered chemically straightening her hair for an academic job interview because she didn’t want her hair to “be a hindrance” when she appeared before White professors.

Dr. Teteh led “The Cost of Beauty,” a hair-health research project published in 2017. She and her team interviewed 91 Black women in Southern California. Some became “combative” at the idea of quitting relaxers and claimed “everything can cause cancer.”

Their reactions speak to the challenges Black women face in America, Dr. Teteh said.

“It’s not that people do not want to hear the information related to their health,” she said. “But they want people to share the information in a way that it’s really empathetic to the plight of being Black here in the United States.”
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

Deanna Denham Hughes was stunned when she was diagnosed with ovarian cancer in 2022. She was only 32. She had no family history of cancer, and tests found no genetic link. Ms. Hughes wondered why she, an otherwise healthy Black mother of two, would develop a malignancy known as a “silent killer.”

After emergency surgery to remove the mass, along with her ovaries, uterus, fallopian tubes, and appendix, Ms. Hughes said, she saw an Instagram post in which a woman with uterine cancer linked her condition to chemical hair straighteners.

“I almost fell over,” she said from her home in Smyrna, Ga.

When Ms. Hughes was about 4, her mother began applying a chemical straightener, or relaxer, to her hair every 6-8 weeks. “It burned, and it smelled awful,” Ms. Hughes recalled. “But it was just part of our routine to ‘deal with my hair.’ ”

The routine continued until she went to college and met other Black women who wore their hair naturally. Soon, Ms. Hughes quit relaxers.

Social and economic pressures have long compelled Black girls and women to straighten their hair to conform to Eurocentric beauty standards. But chemical straighteners are stinky and costly and sometimes cause painful scalp burns. Mounting evidence now shows they could be a health hazard.

Relaxers can contain carcinogens, such as formaldehyde-releasing agents, phthalates, and other endocrine-disrupting compounds, according to National Institutes of Health studies. The compounds can mimic the body’s hormones and have been linked to breast, uterine, and ovarian cancers, studies show.

African American women’s often frequent and lifelong application of chemical relaxers to their hair and scalp might explain why hormone-related cancers kill disproportionately more Black than White women, say researchers and cancer doctors.

“What’s in these products is harmful,” said Tamarra James-Todd, PhD, an epidemiology professor at Harvard T.H. Chan School of Public Health, Boston, who has studied straightening products for the past 20 years.

She believes manufacturers, policymakers, and physicians should warn consumers that relaxers might cause cancer and other health problems.

But regulators have been slow to act, physicians have been reluctant to take up the cause, and racism continues to dictate fashion standards that make it tough for women to quit relaxers, products so addictive they’re known as “creamy crack.”

Michelle Obama straightened her hair when Barack Obama served as president because she believed Americans were “not ready” to see her in braids, the former first lady said after leaving the White House. The U.S. military still prohibited popular Black hairstyles such as dreadlocks and twists while the nation’s first Black president was in office.

California in 2019 became the first of nearly two dozen states to ban race-based hair discrimination. Last year, the U.S. House of Representatives passed similar legislation, known as the CROWN Act, for Creating a Respectful and Open World for Natural Hair. But the bill failed in the Senate.

The need for legislation underscores the challenges Black girls and women face at school and in the workplace.

“You have to pick your struggles,” said Atlanta-based surgical oncologist Ryland J. Gore, MD. She informs her breast cancer patients about the increased cancer risk from relaxers. Despite her knowledge, however, Dr. Gore continues to use chemical straighteners on her own hair, as she has since she was about 7 years old.

“Your hair tells a story,” she said.

In conversations with patients, Dr. Gore sometimes talks about how African American women once wove messages into their braids about the route to take on the Underground Railroad as they sought freedom from slavery.

“It’s just a deep discussion,” one that touches on culture, history, and research into current hairstyling practices, she said. “The data is out there. So patients should be warned, and then they can make a decision.”

The first hint of a connection between hair products and health issues surfaced in the 1990s. Doctors began seeing signs of sexual maturation in Black babies and young girls who developed breasts and pubic hair after using shampoo containing estrogen or placental extract. When the girls stopped using the shampoo, the hair and breast development receded, according to a study published in the journal Clinical Pediatrics in 1998.

Since then, Dr. James-Todd and other researchers have linked chemicals in hair products to a variety of health issues more prevalent among Black women – from early puberty to preterm birth, obesity, and diabetes.

In recent years, researchers have focused on a possible connection between ingredients in chemical relaxers and hormone-related cancers, like the one Ms. Hughes developed, which tend to be more aggressive and deadly in Black women.

A 2017 study found White women who used chemical relaxers were nearly twice as likely to develop breast cancer as those who did not use them. Because the vast majority of the Black study participants used relaxers, researchers could not effectively test the association in Black women, said lead author Adana Llanos, PhD, associate professor of epidemiology at Columbia University’s Mailman School of Public Health, New York.

Researchers did test it in 2020.

The so-called Sister Study, a landmark National Institute of Environmental Health Sciences investigation into the causes of breast cancer and related diseases, followed 50,000 U.S. women whose sisters had been diagnosed with breast cancer and who were cancer-free when they enrolled. Regardless of race, women who reported using relaxers in the prior year were 18% more likely to be diagnosed with breast cancer. Those who used relaxers at least every 5-8 weeks had a 31% higher breast cancer risk.

Nearly 75% of the Black sisters used relaxers in the prior year, compared with 3% of the non-Hispanic White sisters. Three-quarters of Black women self-reported using the straighteners as adolescents, and frequent use of chemical straighteners during adolescence raised the risk of premenopausal breast cancer, a 2021 NIH-funded study in the International Journal of Cancer found.

Another 2021 analysis of the Sister Study data showed sisters who self-reported that they frequently used relaxers or pressing products doubled their ovarian cancer risk. In 2022, another study found frequent use more than doubled uterine cancer risk.

After researchers discovered the link with uterine cancer, some called for policy changes and other measures to reduce exposure to chemical relaxers.

“It is time to intervene,” Dr. Llanos and her colleagues wrote in a Journal of the National Cancer Institute editorial accompanying the uterine cancer analysis. While acknowledging the need for more research, they issued a “call for action.”

No one can say that using permanent hair straighteners will give you cancer, Dr. Llanos said in an interview. “That’s not how cancer works,” she said, noting that some smokers never develop lung cancer, despite tobacco use being a known risk factor.

The body of research linking hair straighteners and cancer is more limited, said Dr. Llanos, who quit using chemical relaxers 15 years ago. But, she asked rhetorically, “Do we need to do the research for 50 more years to know that chemical relaxers are harmful?”

Charlotte R. Gamble, MD, a gynecological oncologist whose Washington, D.C., practice includes Black women with uterine and ovarian cancer, said she and her colleagues see the uterine cancer study findings as worthy of further exploration – but not yet worthy of discussion with patients.

“The jury’s out for me personally,” she said. “There’s so much more data that’s needed.”

Meanwhile, Dr. James-Todd and other researchers believe they have built a solid body of evidence.

“There are enough things we do know to begin taking action, developing interventions, providing useful information to clinicians and patients and the general public,” said Traci N. Bethea, PhD, assistant professor in the Office of Minority Health and Health Disparities Research at Georgetown University.

Responsibility for regulating personal-care products, including chemical hair straighteners and hair dyes – which also have been linked to hormone-related cancers – lies with the Food and Drug Administration. But the FDA does not subject personal-care products to the same approval process it uses for food and drugs. The FDA restricts only 11 categories of chemicals used in cosmetics, while concerns about health effects have prompted the European Union to restrict the use of at least 2,400 substances.

In March, Reps. Ayanna Pressley (D-Mass.) and Shontel Brown (D-Ohio) asked the FDA to investigate the potential health threat posed by chemical relaxers. An FDA representative said the agency would look into it.

Natural hairstyles are enjoying a resurgence among Black girls and women, but many continue to rely on the creamy crack, said Dede Teteh, DrPH, assistant professor of public health at Chapman University, Irvine, Calif.

She had her first straightening perm at 8 and has struggled to withdraw from relaxers as an adult, said Dr. Teteh, who now wears locs. Not long ago, she considered chemically straightening her hair for an academic job interview because she didn’t want her hair to “be a hindrance” when she appeared before White professors.

Dr. Teteh led “The Cost of Beauty,” a hair-health research project published in 2017. She and her team interviewed 91 Black women in Southern California. Some became “combative” at the idea of quitting relaxers and claimed “everything can cause cancer.”

Their reactions speak to the challenges Black women face in America, Dr. Teteh said.

“It’s not that people do not want to hear the information related to their health,” she said. “But they want people to share the information in a way that it’s really empathetic to the plight of being Black here in the United States.”
 

KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – the independent source for health policy research, polling, and journalism.

New imaging tools along with adaptations to existing technologies have been emerging in recent years, with the potential to improve hair diagnostics and treatment monitoring. We provide an overview of 4 noninvasive hair imaging technologies: global photography, trichoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT). For each instrument, we discuss current and future applications in clinical practice and research along with advantages and disadvantages.

Global Photography

Global photography allows for the analysis of hair growth, volume, distribution, and density through serial standardized photographs.¹ Global photography was first introduced for hair growth studies in 1987 and soon after was used for hair and scalp assessments in finasteride clinical trials.²

Hair Assessment—Washed, dried, and combed hair, without hair product, are required for accurate imaging; wet conditions increase reflection and promote hair clumping, thus revealing more scalp and depicting the patient as having less hair.¹ Headshots are taken from short distances and use stereotactic positioning devices to create 4 global views: vertex, midline, frontal, and temporal.³ Stereotactic positioning involves fixing the patient’s chin and forehead as well as mounting the camera and flash device to ensure proper magnification. These adjustments ensure lighting remains consistent throughout consecutive study visits.⁴ Various grading scales are available for use in hair growth clinical studies to increase objectivity in the analysis of serial global photographs. A blinded evaluator should assess the before and after photographs to limit experimenter bias. Global photography often is combined with quantitative software analysis for improved detection of hair changes.¹

Advancements—Growing interest in improving global photography has resulted in various application-based, artificial intelligence (AI)–mediated tools to simplify photograph collection and analysis. For instance, new hair analysis software utilizes AI algorithms to account for facial features in determining the optimal angle for capturing global photographs (Figure 1), which simplifies the generation of global photography images through smartphone applications and obviates the need for additional stereotactic positioning equipment.^5,6

Limitations—Clinicians should be aware of global photography’s requirements for consistency in lighting, camera settings, film, and image processing, which can limit the accuracy of hair assessment over time if not replicated correctly.^7,8 Emerging global photography software has helped to overcome some of these limitations.

Global photography is less precise when a patient’s hair loss is less than 50%, as it is difficult to discern subtle hair changes. Thus, global photography provides limited utility in assessing minimal to moderate hair loss.⁹ Currently, global photography largely functions as an adjunct tool for other hair analysis methods rather than as a stand-alone tool.

Trichoscopy

Trichoscopy (also known as dermoscopy of the hair and scalp) may be performed with a manual dermoscope (with 10× magnification) or a digital videodermatoscope (up to 1000× magnification).^10-12 Unlike global photography, trichoscopy provides a detailed structural analysis of hair shafts, follicular openings, and perifollicular and interfollicular areas.¹³ Kinoshita-Ise and Sachdeva¹³ provided an in-depth, updated review of trichoscopy terminology with their definitions and associated conditions (with prevalence), which should be referenced when performing trichoscopic examination.

Hair Assessment—Trichoscopic assessment begins with inspection of follicular openings (also referred to as “dots”), which vary in color depending on the material filling them—degrading keratinocytes, keratin, sebaceous debris, melanin, or fractured hairs.¹³ The structure of hair shafts also is examined, showing broken hairs, short vellus hairs, and comma hairs, among others. Perifollicular areas are examined for scale, erythema, blue-gray dots, and whitish halos. Interfollicular areas are examined for pigment pattern as well as vascularization, which often presents in a looping configuration under dermoscopy. A combination of dot colorization, hair shaft structure, and perifollicular and interfollicular findings inform diagnostic algorithms of hair and scalp conditions. For example, central centrifugal cicatricial alopecia, the most common alopecia seen in Black women, has been associated with a combination of honeycomb pigment pattern, perifollicular whitish halo, pinpoint white dots, white patches, and perifollicular erythema.¹³

Advantages—Perhaps the most useful feature of trichoscopy is its ability to translate visualized features into simple diagnostic algorithms. For instance, if the clinician has diagnosed the patient with noncicatricial alopecia, they would next focus on dot colors. With black dots, the next step would be to determine whether the hairs are tapered or coiled, and so on. This systematic approach enables the clinician to narrow possible diagnoses.² An additional advantage of trichoscopy is that it examines large surface areas noninvasively as compared to hair-pull tests and scalp biopsy.^14,15 Trichoscopy allows temporal comparisons of the same area for disease and treatment monitoring with more diagnostic detail than global photography.¹⁶ Trichoscopy also is useful in selecting biopsy locations by discerning and avoiding areas of scar tissue.¹⁷

Limitations—Diagnosis via the trichoscopy algorithm is limiting because it is not comprehensive of all hair and scalp disease.¹⁸ Additionally, many pathologies exhibit overlapping follicular and interfollicular patterning. For example, almost all subtypes of scarring alopecia present with hair loss and scarred follicles once they have progressed to advanced stages. Further studies should identify more specific patterns of hair and scalp pathologies, which could then be incorporated into a diagnostic algorithm.¹³

Advancements—The advent of hair analysis software has expanded the role of videodermoscopy by rapidly quantifying hair growth parameters such as hair count, follicular density, and follicular diameter, as well as interfollicular distances (Figure 2).^14,17 Vellus and terminal hairs are differentiated according to their thickness and length.¹⁷ Moreover, the software can analyze the same area of the scalp over time by either virtual tattoos, semipermanent markings, or precise location measurements, increasing intra- and interclass correlation. The rate of hair growth, hair shedding, and parameters of anagen and telogen hairs can be studied by a method termed phototrichogram whereby a transitional area of hair loss and normal hair growth is identified and trimmed to less than 1 mm from the skin surface.¹⁹ A baseline photograph is taken using videodermoscopy. After approximately 3 days, the identical region is photographed and compared with the initial image to observe changes in the hair. Software programs can distinguish the growing hair as anagen and nongrowing hair as telogen, calculating the anagen-to-telogen ratio as well as hair growth rate, which are essential measurements in hair research and clinical studies. Software programs have replaced laborious and time-consuming manual hair counts and have rapidly grown in popularity in evaluating patterned hair loss.

Reflectance Confocal Microscopy

Reflectance confocal microscopy is a noninvasive imaging tool that visualizes skin and its appendages at near-histologic resolution (lateral resolution of 0.5–1 μm). It produces grayscale horizontal images that can be taken at levels ranging from the stratum corneum to the superficial papillary dermis, corresponding to a depth of approximately 100 to 150 µm. Thus, a hair follicle can be imaged starting from the follicular ostia down to the reachable papillary dermis (Figure 3).²⁰ Image contrast is provided by differences in the size and refractive indices of cellular organelles.^21,22 There are 2 commercially available RCM devices: VivaScope 1500 and VivaScope 3000 (Caliber Imaging & Diagnostics, Inc).

VivaScope 1500, a wide-probe microscope, requires the attachment of a plastic window to the desired imaging area. The plastic window is lined with medical adhesive tape to prevent movement during imaging. The adhesive tape can pull on hair upon removal, which is not ideal for patients with existing hair loss. Additionally, the image quality of VivaSope 1500 is best in flat areas and areas where hair is shaved.^20,23,24 Despite these disadvantages, VivaScope 1500 has successfully shown utility in research studies, which suggests that these obstacles can be overcome by experienced users. The handheld VivaScope 3000 is ergonomically designed and suitable for curved surfaces such as the scalp, with the advantage of not requiring any adhesive. However, the images acquired from the VivaScope 3000 cover a smaller surface area.

Structures Visualized—Structures distinguished with RCM include keratinocytes, melanocytes, inflammatory cells, hair follicles, hair shafts, adnexal infundibular epithelium, blood vessels, fibroblasts, and collagen.²³ Real-time visualization of blood flow also can be seen.

Applications of RCM—Reflectance confocal microscopy has been used to study scalp discoid lupus, lichen planopilaris, frontal fibrosing alopecia, folliculitis decalvans, chemotherapy-induced alopecia (CIA), alopecia areata, and androgenetic alopecia. Diagnostic RCM criteria for such alopecias have been developed based on their correspondence to histopathology. An RCM study of classic lichen planopilaris and frontal fibrosing alopecia identified features of epidermal disarray, infundibular hyperkeratosis, inflammatory cells, pigment incontinence, perifollicular fibrosis, bandlike scarring, melanophages in the dermis, dilated blood vessels, basal layer vacuolar degeneration, and necrotic keratinocytes.²⁵ Pigment incontinence in the superficial epidermis, perifollicular lichenoid inflammation, and hyperkeratosis were characteristic RCM features of early-stage lichen planopilaris, while perifollicular fibrosis and dilated blood vessels were characteristic RCM features of late-stage disease. The ability of RCM features to distinguish different stages of lichen planopilaris shows its potential in treating early disease and preventing irreversible hair loss.

Differentiating between scarring and nonscarring alopecia also is possible through RCM. The presence of periadnexal, epidermal, and dermal inflammatory cells, in addition to periadnexal sclerosis, are defining RCM features of scarring alopecia.²⁶ These features are absent in nonscarring alopecias. Reflectance confocal microscopy additionally has been shown to be useful in the treatment monitoring of lichen planopilaris and discoid lupus erythematosus.²⁰ Independent reviewers, blinded to the patients’ identities, were able to characterize and follow features of these scarring alopecias by RCM. The assessed RCM features were comparable to those observed by histopathologic evaluation: epidermal disarray, spongiosis, exocytosis of inflammatory cells in the epidermis, interface dermatitis, peri- and intra-adnexal infiltration of inflammatory cells, dilated vessels in the dermis, dermal infiltration of inflammatory cells and melanophages, and dermal sclerosis. A reduction in inflammatory cells across multiple skin layers and at the level of the adnexal epithelium correlated with clinical response to treatment. Reflectance confocal microscopy also was able to detect recurrence of inflammation in cases where treatment had been interrupted before clinical signs of disease recurrence were evident. The authors thus concluded that RCM’s sensitivity can guide timing of treatment and avoid delays in starting or restarting treatment.²⁰

Reflectance confocal microscopy also has served as a learning tool for new subclinical understandings of alopecia. In a study of CIA, the disease was found to be a dynamic process that could be categorized into 4 distinct phases distinguishable by combined confocal and dermoscopic features. This study also identified a new feature observable on RCM images—a CIA dot—defined as a dilated follicular infundibulum containing mashed, malted, nonhomogeneous material and normal or fragmented hair. This dot is thought to represent the initial microscopic sign of direct toxicity of chemotherapy on the hair follicle. Chemotherapy-induced alopecia dots persist throughout chemotherapy and subsequently disappear after chemotherapy ends.²⁷

Limitations and Advantages—Currently, subtypes of cicatricial alopecias cannot be characterized on RCM because inflammatory cell types are not distinguished from each other (eg, eosinophils vs neutrophils). Another limitation of RCM is the loss of resolution below the superficial papillary dermis (a depth of approximately 150 µm); thus, deeper structures, such as the hair bulb, cannot be visualized.

Unlike global photography and trichoscopy, which are low-cost methods, RCM is much more costly, ranging upwards of several thousand dollars, and it may require additional technical support fees, making it less accessible for clinical practice. However, RCM imaging continues to be recommended as an intermediate step between trichoscopy and histology for the diagnosis and management of hair disease.²⁶ If a biopsy is required, RCM can aid in the selection of a biopsy site, as areas with active inflammation are more informative than atrophic and fibrosed areas.²³ The role of RCM in trichoscopy can be expanded by designing a more cost-effective and ergonomically suited scope for hair and scalp assessment.

Optical Coherence Tomography

Optical coherence tomography is a noninvasive handheld device that emits low-power infrared light to visualize the skin and adnexal structures. Optical coherence tomography relies on the principle of interferometry to detect phase differences in optical backscattering at varying tissue depths.^28,29 It allows visualization up to 2 mm, which is 2 to 5 times deeper than RCM.³⁶ Unlike RCM, which has cellular resolution, OCT has an axial resolution of 3 to 15 μm, which allows only for the detection of structural boundaries.³⁰ There are various OCT modalities that differ in lateral and axial resolutions and maximum depth. Commercial software is available that measures changes in vascular density by depth, epidermal thickness, skin surface texture, and optical attenuation—the latter being an indirect measurement of collagen density and skin hydration.

Structures Visualized—Hair follicles can be well distinguished on OCT images, and as such, OCT is recognized as a diagnostic tool in trichology (Figure 4).³¹ Follicular openings, interfollicular collagen, and outlines of the hair shafts are visible; however, detailed components of the follicular unit cannot be visualized by OCT. Keratin hyperrefractivity identifies the hair shaft. Additionally, the hair matrix is denoted by a slightly granular texture in the dermis. Dynamic OCT produces colorized images that visualize blood flow within vessels.

Applications of OCT—Optical coherence tomography is utilized in investigative trichology because it provides highly reproducible measurements of hair shaft diameters, cross-sectional surface areas, and form factor, which is a surrogate parameter for hair shape. The cross-section of hair shafts provides insight into local metabolism and perifollicular inflammation. Cross-sections of hair shafts in areas of alopecia areata were found to be smaller than cross-sections in the unaffected scalp within the same individual.³² Follicular density can be manually quantified on OCT images, but there also is promise for automated quantification. A recent study by Urban et al³³ described training a convolutional neural network to automatically count hair as well as hair-bearing and non–hair-bearing follicles in OCT scans. These investigators also were able to color-code hair according to height, resulting in the creation of a “height” map.

Optical coherence tomography has furthered our understanding of the pathophysiology of cicatricial and nonscarring alopecias. Vazquez-Herrera et al³⁴ assessed the inflammatory and cicatricial stages of frontal fibrosing alopecia by OCT imaging. Inflammatory hairlines, which are seen in the early stages of frontal fibrosing alopecia, exhibited a thickened dermis, irregular distribution of collagen, and increased vascularity in both the superficial and deep dermal layers compared to cicatricial and healthy scalp. Conversely, late-stage cicatricial areas exhibited a thin dermis and collagen that appeared in a hyperreflective, concentric, onion-shaped pattern around remnant follicular openings. Vascular flow was reduced in the superficial dermis of a cicatricial scalp but increased in the deep dermal layers compared with a healthy scalp. The attenuation coefficients of these disease stages also were assessed. The attenuation coefficient of the inflammatory hairline was higher compared with normal skin, likely as a reflection of inflammatory infiltrate and edema, whereas the attenuation coefficient of cicatricial scalp was lower compared with normal skin, likely reflecting the reduced water content of atrophic skin.³⁴ This differentiation of early- and late-stage cicatricial alopecias has implications for early treatment and improved prognosis. Additionally, there is potential for OCT to assist in the differentiation of alopecia subtypes, as it can measure the epidermal thickness and follicular density and was previously used to compare scarring and nonscarring alopecia.³⁵

Advantages and Limitations—Similar to RCM, OCT may be cost prohibitive for some clinicians. In addition, OCT cannot visualize the follicular unit in cellular detail. However, the extent of OCT’s capabilities may not be fully realized. Dynamic OCT is a new angiographic type of OCT that shows potential in monitoring early subclinical responses to novel alopecia therapies, such as platelet-rich plasminogen, which is hypothesized to stimulate hair growth through angiogenesis. Additionally, OCT may improve outcomes of hair transplantation procedures by allowing for visualization of the subcutaneous angle of hair follicles. Blind extraction of hair follicles in follicular unit extraction procedures can result in inadvertent transection and damage to the hair follicle; OCT could help identify good candidates for follicular unit extraction, such as patients with hair follicles in parallel arrangement, who are predicted to have better results.³⁶

Conclusion

The field of trichology will continue to evolve with the emergence of noninvasive imaging technologies that diagnose hair disease in early stages and enable treatment monitoring with quantification of hair parameters. As discussed in this review, global photography, trichoscopy, RCM, and OCT have furthered our understanding of alopecia pathophysiology and provided objective methods of treatment evaluation. The capabilities of these tools will continue to expand with advancements in add-on software and AI algorithms.

New imaging tools along with adaptations to existing technologies have been emerging in recent years, with the potential to improve hair diagnostics and treatment monitoring. We provide an overview of 4 noninvasive hair imaging technologies: global photography, trichoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT). For each instrument, we discuss current and future applications in clinical practice and research along with advantages and disadvantages.

Global Photography

Global photography allows for the analysis of hair growth, volume, distribution, and density through serial standardized photographs.¹ Global photography was first introduced for hair growth studies in 1987 and soon after was used for hair and scalp assessments in finasteride clinical trials.²

Hair Assessment—Washed, dried, and combed hair, without hair product, are required for accurate imaging; wet conditions increase reflection and promote hair clumping, thus revealing more scalp and depicting the patient as having less hair.¹ Headshots are taken from short distances and use stereotactic positioning devices to create 4 global views: vertex, midline, frontal, and temporal.³ Stereotactic positioning involves fixing the patient’s chin and forehead as well as mounting the camera and flash device to ensure proper magnification. These adjustments ensure lighting remains consistent throughout consecutive study visits.⁴ Various grading scales are available for use in hair growth clinical studies to increase objectivity in the analysis of serial global photographs. A blinded evaluator should assess the before and after photographs to limit experimenter bias. Global photography often is combined with quantitative software analysis for improved detection of hair changes.¹

Advancements—Growing interest in improving global photography has resulted in various application-based, artificial intelligence (AI)–mediated tools to simplify photograph collection and analysis. For instance, new hair analysis software utilizes AI algorithms to account for facial features in determining the optimal angle for capturing global photographs (Figure 1), which simplifies the generation of global photography images through smartphone applications and obviates the need for additional stereotactic positioning equipment.^5,6

Limitations—Clinicians should be aware of global photography’s requirements for consistency in lighting, camera settings, film, and image processing, which can limit the accuracy of hair assessment over time if not replicated correctly.^7,8 Emerging global photography software has helped to overcome some of these limitations.

Global photography is less precise when a patient’s hair loss is less than 50%, as it is difficult to discern subtle hair changes. Thus, global photography provides limited utility in assessing minimal to moderate hair loss.⁹ Currently, global photography largely functions as an adjunct tool for other hair analysis methods rather than as a stand-alone tool.

Trichoscopy

Trichoscopy (also known as dermoscopy of the hair and scalp) may be performed with a manual dermoscope (with 10× magnification) or a digital videodermatoscope (up to 1000× magnification).^10-12 Unlike global photography, trichoscopy provides a detailed structural analysis of hair shafts, follicular openings, and perifollicular and interfollicular areas.¹³ Kinoshita-Ise and Sachdeva¹³ provided an in-depth, updated review of trichoscopy terminology with their definitions and associated conditions (with prevalence), which should be referenced when performing trichoscopic examination.

Hair Assessment—Trichoscopic assessment begins with inspection of follicular openings (also referred to as “dots”), which vary in color depending on the material filling them—degrading keratinocytes, keratin, sebaceous debris, melanin, or fractured hairs.¹³ The structure of hair shafts also is examined, showing broken hairs, short vellus hairs, and comma hairs, among others. Perifollicular areas are examined for scale, erythema, blue-gray dots, and whitish halos. Interfollicular areas are examined for pigment pattern as well as vascularization, which often presents in a looping configuration under dermoscopy. A combination of dot colorization, hair shaft structure, and perifollicular and interfollicular findings inform diagnostic algorithms of hair and scalp conditions. For example, central centrifugal cicatricial alopecia, the most common alopecia seen in Black women, has been associated with a combination of honeycomb pigment pattern, perifollicular whitish halo, pinpoint white dots, white patches, and perifollicular erythema.¹³

Advantages—Perhaps the most useful feature of trichoscopy is its ability to translate visualized features into simple diagnostic algorithms. For instance, if the clinician has diagnosed the patient with noncicatricial alopecia, they would next focus on dot colors. With black dots, the next step would be to determine whether the hairs are tapered or coiled, and so on. This systematic approach enables the clinician to narrow possible diagnoses.² An additional advantage of trichoscopy is that it examines large surface areas noninvasively as compared to hair-pull tests and scalp biopsy.^14,15 Trichoscopy allows temporal comparisons of the same area for disease and treatment monitoring with more diagnostic detail than global photography.¹⁶ Trichoscopy also is useful in selecting biopsy locations by discerning and avoiding areas of scar tissue.¹⁷

Limitations—Diagnosis via the trichoscopy algorithm is limiting because it is not comprehensive of all hair and scalp disease.¹⁸ Additionally, many pathologies exhibit overlapping follicular and interfollicular patterning. For example, almost all subtypes of scarring alopecia present with hair loss and scarred follicles once they have progressed to advanced stages. Further studies should identify more specific patterns of hair and scalp pathologies, which could then be incorporated into a diagnostic algorithm.¹³

Advancements—The advent of hair analysis software has expanded the role of videodermoscopy by rapidly quantifying hair growth parameters such as hair count, follicular density, and follicular diameter, as well as interfollicular distances (Figure 2).^14,17 Vellus and terminal hairs are differentiated according to their thickness and length.¹⁷ Moreover, the software can analyze the same area of the scalp over time by either virtual tattoos, semipermanent markings, or precise location measurements, increasing intra- and interclass correlation. The rate of hair growth, hair shedding, and parameters of anagen and telogen hairs can be studied by a method termed phototrichogram whereby a transitional area of hair loss and normal hair growth is identified and trimmed to less than 1 mm from the skin surface.¹⁹ A baseline photograph is taken using videodermoscopy. After approximately 3 days, the identical region is photographed and compared with the initial image to observe changes in the hair. Software programs can distinguish the growing hair as anagen and nongrowing hair as telogen, calculating the anagen-to-telogen ratio as well as hair growth rate, which are essential measurements in hair research and clinical studies. Software programs have replaced laborious and time-consuming manual hair counts and have rapidly grown in popularity in evaluating patterned hair loss.

Reflectance Confocal Microscopy

Reflectance confocal microscopy is a noninvasive imaging tool that visualizes skin and its appendages at near-histologic resolution (lateral resolution of 0.5–1 μm). It produces grayscale horizontal images that can be taken at levels ranging from the stratum corneum to the superficial papillary dermis, corresponding to a depth of approximately 100 to 150 µm. Thus, a hair follicle can be imaged starting from the follicular ostia down to the reachable papillary dermis (Figure 3).²⁰ Image contrast is provided by differences in the size and refractive indices of cellular organelles.^21,22 There are 2 commercially available RCM devices: VivaScope 1500 and VivaScope 3000 (Caliber Imaging & Diagnostics, Inc).

VivaScope 1500, a wide-probe microscope, requires the attachment of a plastic window to the desired imaging area. The plastic window is lined with medical adhesive tape to prevent movement during imaging. The adhesive tape can pull on hair upon removal, which is not ideal for patients with existing hair loss. Additionally, the image quality of VivaSope 1500 is best in flat areas and areas where hair is shaved.^20,23,24 Despite these disadvantages, VivaScope 1500 has successfully shown utility in research studies, which suggests that these obstacles can be overcome by experienced users. The handheld VivaScope 3000 is ergonomically designed and suitable for curved surfaces such as the scalp, with the advantage of not requiring any adhesive. However, the images acquired from the VivaScope 3000 cover a smaller surface area.

Structures Visualized—Structures distinguished with RCM include keratinocytes, melanocytes, inflammatory cells, hair follicles, hair shafts, adnexal infundibular epithelium, blood vessels, fibroblasts, and collagen.²³ Real-time visualization of blood flow also can be seen.

Applications of RCM—Reflectance confocal microscopy has been used to study scalp discoid lupus, lichen planopilaris, frontal fibrosing alopecia, folliculitis decalvans, chemotherapy-induced alopecia (CIA), alopecia areata, and androgenetic alopecia. Diagnostic RCM criteria for such alopecias have been developed based on their correspondence to histopathology. An RCM study of classic lichen planopilaris and frontal fibrosing alopecia identified features of epidermal disarray, infundibular hyperkeratosis, inflammatory cells, pigment incontinence, perifollicular fibrosis, bandlike scarring, melanophages in the dermis, dilated blood vessels, basal layer vacuolar degeneration, and necrotic keratinocytes.²⁵ Pigment incontinence in the superficial epidermis, perifollicular lichenoid inflammation, and hyperkeratosis were characteristic RCM features of early-stage lichen planopilaris, while perifollicular fibrosis and dilated blood vessels were characteristic RCM features of late-stage disease. The ability of RCM features to distinguish different stages of lichen planopilaris shows its potential in treating early disease and preventing irreversible hair loss.

Differentiating between scarring and nonscarring alopecia also is possible through RCM. The presence of periadnexal, epidermal, and dermal inflammatory cells, in addition to periadnexal sclerosis, are defining RCM features of scarring alopecia.²⁶ These features are absent in nonscarring alopecias. Reflectance confocal microscopy additionally has been shown to be useful in the treatment monitoring of lichen planopilaris and discoid lupus erythematosus.²⁰ Independent reviewers, blinded to the patients’ identities, were able to characterize and follow features of these scarring alopecias by RCM. The assessed RCM features were comparable to those observed by histopathologic evaluation: epidermal disarray, spongiosis, exocytosis of inflammatory cells in the epidermis, interface dermatitis, peri- and intra-adnexal infiltration of inflammatory cells, dilated vessels in the dermis, dermal infiltration of inflammatory cells and melanophages, and dermal sclerosis. A reduction in inflammatory cells across multiple skin layers and at the level of the adnexal epithelium correlated with clinical response to treatment. Reflectance confocal microscopy also was able to detect recurrence of inflammation in cases where treatment had been interrupted before clinical signs of disease recurrence were evident. The authors thus concluded that RCM’s sensitivity can guide timing of treatment and avoid delays in starting or restarting treatment.²⁰

Reflectance confocal microscopy also has served as a learning tool for new subclinical understandings of alopecia. In a study of CIA, the disease was found to be a dynamic process that could be categorized into 4 distinct phases distinguishable by combined confocal and dermoscopic features. This study also identified a new feature observable on RCM images—a CIA dot—defined as a dilated follicular infundibulum containing mashed, malted, nonhomogeneous material and normal or fragmented hair. This dot is thought to represent the initial microscopic sign of direct toxicity of chemotherapy on the hair follicle. Chemotherapy-induced alopecia dots persist throughout chemotherapy and subsequently disappear after chemotherapy ends.²⁷

Limitations and Advantages—Currently, subtypes of cicatricial alopecias cannot be characterized on RCM because inflammatory cell types are not distinguished from each other (eg, eosinophils vs neutrophils). Another limitation of RCM is the loss of resolution below the superficial papillary dermis (a depth of approximately 150 µm); thus, deeper structures, such as the hair bulb, cannot be visualized.

Unlike global photography and trichoscopy, which are low-cost methods, RCM is much more costly, ranging upwards of several thousand dollars, and it may require additional technical support fees, making it less accessible for clinical practice. However, RCM imaging continues to be recommended as an intermediate step between trichoscopy and histology for the diagnosis and management of hair disease.²⁶ If a biopsy is required, RCM can aid in the selection of a biopsy site, as areas with active inflammation are more informative than atrophic and fibrosed areas.²³ The role of RCM in trichoscopy can be expanded by designing a more cost-effective and ergonomically suited scope for hair and scalp assessment.

Optical Coherence Tomography

Optical coherence tomography is a noninvasive handheld device that emits low-power infrared light to visualize the skin and adnexal structures. Optical coherence tomography relies on the principle of interferometry to detect phase differences in optical backscattering at varying tissue depths.^28,29 It allows visualization up to 2 mm, which is 2 to 5 times deeper than RCM.³⁶ Unlike RCM, which has cellular resolution, OCT has an axial resolution of 3 to 15 μm, which allows only for the detection of structural boundaries.³⁰ There are various OCT modalities that differ in lateral and axial resolutions and maximum depth. Commercial software is available that measures changes in vascular density by depth, epidermal thickness, skin surface texture, and optical attenuation—the latter being an indirect measurement of collagen density and skin hydration.

Structures Visualized—Hair follicles can be well distinguished on OCT images, and as such, OCT is recognized as a diagnostic tool in trichology (Figure 4).³¹ Follicular openings, interfollicular collagen, and outlines of the hair shafts are visible; however, detailed components of the follicular unit cannot be visualized by OCT. Keratin hyperrefractivity identifies the hair shaft. Additionally, the hair matrix is denoted by a slightly granular texture in the dermis. Dynamic OCT produces colorized images that visualize blood flow within vessels.

Applications of OCT—Optical coherence tomography is utilized in investigative trichology because it provides highly reproducible measurements of hair shaft diameters, cross-sectional surface areas, and form factor, which is a surrogate parameter for hair shape. The cross-section of hair shafts provides insight into local metabolism and perifollicular inflammation. Cross-sections of hair shafts in areas of alopecia areata were found to be smaller than cross-sections in the unaffected scalp within the same individual.³² Follicular density can be manually quantified on OCT images, but there also is promise for automated quantification. A recent study by Urban et al³³ described training a convolutional neural network to automatically count hair as well as hair-bearing and non–hair-bearing follicles in OCT scans. These investigators also were able to color-code hair according to height, resulting in the creation of a “height” map.

Optical coherence tomography has furthered our understanding of the pathophysiology of cicatricial and nonscarring alopecias. Vazquez-Herrera et al³⁴ assessed the inflammatory and cicatricial stages of frontal fibrosing alopecia by OCT imaging. Inflammatory hairlines, which are seen in the early stages of frontal fibrosing alopecia, exhibited a thickened dermis, irregular distribution of collagen, and increased vascularity in both the superficial and deep dermal layers compared to cicatricial and healthy scalp. Conversely, late-stage cicatricial areas exhibited a thin dermis and collagen that appeared in a hyperreflective, concentric, onion-shaped pattern around remnant follicular openings. Vascular flow was reduced in the superficial dermis of a cicatricial scalp but increased in the deep dermal layers compared with a healthy scalp. The attenuation coefficients of these disease stages also were assessed. The attenuation coefficient of the inflammatory hairline was higher compared with normal skin, likely as a reflection of inflammatory infiltrate and edema, whereas the attenuation coefficient of cicatricial scalp was lower compared with normal skin, likely reflecting the reduced water content of atrophic skin.³⁴ This differentiation of early- and late-stage cicatricial alopecias has implications for early treatment and improved prognosis. Additionally, there is potential for OCT to assist in the differentiation of alopecia subtypes, as it can measure the epidermal thickness and follicular density and was previously used to compare scarring and nonscarring alopecia.³⁵

Advantages and Limitations—Similar to RCM, OCT may be cost prohibitive for some clinicians. In addition, OCT cannot visualize the follicular unit in cellular detail. However, the extent of OCT’s capabilities may not be fully realized. Dynamic OCT is a new angiographic type of OCT that shows potential in monitoring early subclinical responses to novel alopecia therapies, such as platelet-rich plasminogen, which is hypothesized to stimulate hair growth through angiogenesis. Additionally, OCT may improve outcomes of hair transplantation procedures by allowing for visualization of the subcutaneous angle of hair follicles. Blind extraction of hair follicles in follicular unit extraction procedures can result in inadvertent transection and damage to the hair follicle; OCT could help identify good candidates for follicular unit extraction, such as patients with hair follicles in parallel arrangement, who are predicted to have better results.³⁶

Conclusion

The field of trichology will continue to evolve with the emergence of noninvasive imaging technologies that diagnose hair disease in early stages and enable treatment monitoring with quantification of hair parameters. As discussed in this review, global photography, trichoscopy, RCM, and OCT have furthered our understanding of alopecia pathophysiology and provided objective methods of treatment evaluation. The capabilities of these tools will continue to expand with advancements in add-on software and AI algorithms.

New imaging tools along with adaptations to existing technologies have been emerging in recent years, with the potential to improve hair diagnostics and treatment monitoring. We provide an overview of 4 noninvasive hair imaging technologies: global photography, trichoscopy, reflectance confocal microscopy (RCM), and optical coherence tomography (OCT). For each instrument, we discuss current and future applications in clinical practice and research along with advantages and disadvantages.

Global Photography

Global photography allows for the analysis of hair growth, volume, distribution, and density through serial standardized photographs.¹ Global photography was first introduced for hair growth studies in 1987 and soon after was used for hair and scalp assessments in finasteride clinical trials.²

Hair Assessment—Washed, dried, and combed hair, without hair product, are required for accurate imaging; wet conditions increase reflection and promote hair clumping, thus revealing more scalp and depicting the patient as having less hair.¹ Headshots are taken from short distances and use stereotactic positioning devices to create 4 global views: vertex, midline, frontal, and temporal.³ Stereotactic positioning involves fixing the patient’s chin and forehead as well as mounting the camera and flash device to ensure proper magnification. These adjustments ensure lighting remains consistent throughout consecutive study visits.⁴ Various grading scales are available for use in hair growth clinical studies to increase objectivity in the analysis of serial global photographs. A blinded evaluator should assess the before and after photographs to limit experimenter bias. Global photography often is combined with quantitative software analysis for improved detection of hair changes.¹

Advancements—Growing interest in improving global photography has resulted in various application-based, artificial intelligence (AI)–mediated tools to simplify photograph collection and analysis. For instance, new hair analysis software utilizes AI algorithms to account for facial features in determining the optimal angle for capturing global photographs (Figure 1), which simplifies the generation of global photography images through smartphone applications and obviates the need for additional stereotactic positioning equipment.^5,6

Limitations—Clinicians should be aware of global photography’s requirements for consistency in lighting, camera settings, film, and image processing, which can limit the accuracy of hair assessment over time if not replicated correctly.^7,8 Emerging global photography software has helped to overcome some of these limitations.

Global photography is less precise when a patient’s hair loss is less than 50%, as it is difficult to discern subtle hair changes. Thus, global photography provides limited utility in assessing minimal to moderate hair loss.⁹ Currently, global photography largely functions as an adjunct tool for other hair analysis methods rather than as a stand-alone tool.

Trichoscopy

Trichoscopy (also known as dermoscopy of the hair and scalp) may be performed with a manual dermoscope (with 10× magnification) or a digital videodermatoscope (up to 1000× magnification).^10-12 Unlike global photography, trichoscopy provides a detailed structural analysis of hair shafts, follicular openings, and perifollicular and interfollicular areas.¹³ Kinoshita-Ise and Sachdeva¹³ provided an in-depth, updated review of trichoscopy terminology with their definitions and associated conditions (with prevalence), which should be referenced when performing trichoscopic examination.

Hair Assessment—Trichoscopic assessment begins with inspection of follicular openings (also referred to as “dots”), which vary in color depending on the material filling them—degrading keratinocytes, keratin, sebaceous debris, melanin, or fractured hairs.¹³ The structure of hair shafts also is examined, showing broken hairs, short vellus hairs, and comma hairs, among others. Perifollicular areas are examined for scale, erythema, blue-gray dots, and whitish halos. Interfollicular areas are examined for pigment pattern as well as vascularization, which often presents in a looping configuration under dermoscopy. A combination of dot colorization, hair shaft structure, and perifollicular and interfollicular findings inform diagnostic algorithms of hair and scalp conditions. For example, central centrifugal cicatricial alopecia, the most common alopecia seen in Black women, has been associated with a combination of honeycomb pigment pattern, perifollicular whitish halo, pinpoint white dots, white patches, and perifollicular erythema.¹³

Advantages—Perhaps the most useful feature of trichoscopy is its ability to translate visualized features into simple diagnostic algorithms. For instance, if the clinician has diagnosed the patient with noncicatricial alopecia, they would next focus on dot colors. With black dots, the next step would be to determine whether the hairs are tapered or coiled, and so on. This systematic approach enables the clinician to narrow possible diagnoses.² An additional advantage of trichoscopy is that it examines large surface areas noninvasively as compared to hair-pull tests and scalp biopsy.^14,15 Trichoscopy allows temporal comparisons of the same area for disease and treatment monitoring with more diagnostic detail than global photography.¹⁶ Trichoscopy also is useful in selecting biopsy locations by discerning and avoiding areas of scar tissue.¹⁷

Limitations—Diagnosis via the trichoscopy algorithm is limiting because it is not comprehensive of all hair and scalp disease.¹⁸ Additionally, many pathologies exhibit overlapping follicular and interfollicular patterning. For example, almost all subtypes of scarring alopecia present with hair loss and scarred follicles once they have progressed to advanced stages. Further studies should identify more specific patterns of hair and scalp pathologies, which could then be incorporated into a diagnostic algorithm.¹³

Advancements—The advent of hair analysis software has expanded the role of videodermoscopy by rapidly quantifying hair growth parameters such as hair count, follicular density, and follicular diameter, as well as interfollicular distances (Figure 2).^14,17 Vellus and terminal hairs are differentiated according to their thickness and length.¹⁷ Moreover, the software can analyze the same area of the scalp over time by either virtual tattoos, semipermanent markings, or precise location measurements, increasing intra- and interclass correlation. The rate of hair growth, hair shedding, and parameters of anagen and telogen hairs can be studied by a method termed phototrichogram whereby a transitional area of hair loss and normal hair growth is identified and trimmed to less than 1 mm from the skin surface.¹⁹ A baseline photograph is taken using videodermoscopy. After approximately 3 days, the identical region is photographed and compared with the initial image to observe changes in the hair. Software programs can distinguish the growing hair as anagen and nongrowing hair as telogen, calculating the anagen-to-telogen ratio as well as hair growth rate, which are essential measurements in hair research and clinical studies. Software programs have replaced laborious and time-consuming manual hair counts and have rapidly grown in popularity in evaluating patterned hair loss.

Reflectance Confocal Microscopy

Reflectance confocal microscopy is a noninvasive imaging tool that visualizes skin and its appendages at near-histologic resolution (lateral resolution of 0.5–1 μm). It produces grayscale horizontal images that can be taken at levels ranging from the stratum corneum to the superficial papillary dermis, corresponding to a depth of approximately 100 to 150 µm. Thus, a hair follicle can be imaged starting from the follicular ostia down to the reachable papillary dermis (Figure 3).²⁰ Image contrast is provided by differences in the size and refractive indices of cellular organelles.^21,22 There are 2 commercially available RCM devices: VivaScope 1500 and VivaScope 3000 (Caliber Imaging & Diagnostics, Inc).

VivaScope 1500, a wide-probe microscope, requires the attachment of a plastic window to the desired imaging area. The plastic window is lined with medical adhesive tape to prevent movement during imaging. The adhesive tape can pull on hair upon removal, which is not ideal for patients with existing hair loss. Additionally, the image quality of VivaSope 1500 is best in flat areas and areas where hair is shaved.^20,23,24 Despite these disadvantages, VivaScope 1500 has successfully shown utility in research studies, which suggests that these obstacles can be overcome by experienced users. The handheld VivaScope 3000 is ergonomically designed and suitable for curved surfaces such as the scalp, with the advantage of not requiring any adhesive. However, the images acquired from the VivaScope 3000 cover a smaller surface area.

Structures Visualized—Structures distinguished with RCM include keratinocytes, melanocytes, inflammatory cells, hair follicles, hair shafts, adnexal infundibular epithelium, blood vessels, fibroblasts, and collagen.²³ Real-time visualization of blood flow also can be seen.

Applications of RCM—Reflectance confocal microscopy has been used to study scalp discoid lupus, lichen planopilaris, frontal fibrosing alopecia, folliculitis decalvans, chemotherapy-induced alopecia (CIA), alopecia areata, and androgenetic alopecia. Diagnostic RCM criteria for such alopecias have been developed based on their correspondence to histopathology. An RCM study of classic lichen planopilaris and frontal fibrosing alopecia identified features of epidermal disarray, infundibular hyperkeratosis, inflammatory cells, pigment incontinence, perifollicular fibrosis, bandlike scarring, melanophages in the dermis, dilated blood vessels, basal layer vacuolar degeneration, and necrotic keratinocytes.²⁵ Pigment incontinence in the superficial epidermis, perifollicular lichenoid inflammation, and hyperkeratosis were characteristic RCM features of early-stage lichen planopilaris, while perifollicular fibrosis and dilated blood vessels were characteristic RCM features of late-stage disease. The ability of RCM features to distinguish different stages of lichen planopilaris shows its potential in treating early disease and preventing irreversible hair loss.

Differentiating between scarring and nonscarring alopecia also is possible through RCM. The presence of periadnexal, epidermal, and dermal inflammatory cells, in addition to periadnexal sclerosis, are defining RCM features of scarring alopecia.²⁶ These features are absent in nonscarring alopecias. Reflectance confocal microscopy additionally has been shown to be useful in the treatment monitoring of lichen planopilaris and discoid lupus erythematosus.²⁰ Independent reviewers, blinded to the patients’ identities, were able to characterize and follow features of these scarring alopecias by RCM. The assessed RCM features were comparable to those observed by histopathologic evaluation: epidermal disarray, spongiosis, exocytosis of inflammatory cells in the epidermis, interface dermatitis, peri- and intra-adnexal infiltration of inflammatory cells, dilated vessels in the dermis, dermal infiltration of inflammatory cells and melanophages, and dermal sclerosis. A reduction in inflammatory cells across multiple skin layers and at the level of the adnexal epithelium correlated with clinical response to treatment. Reflectance confocal microscopy also was able to detect recurrence of inflammation in cases where treatment had been interrupted before clinical signs of disease recurrence were evident. The authors thus concluded that RCM’s sensitivity can guide timing of treatment and avoid delays in starting or restarting treatment.²⁰

Reflectance confocal microscopy also has served as a learning tool for new subclinical understandings of alopecia. In a study of CIA, the disease was found to be a dynamic process that could be categorized into 4 distinct phases distinguishable by combined confocal and dermoscopic features. This study also identified a new feature observable on RCM images—a CIA dot—defined as a dilated follicular infundibulum containing mashed, malted, nonhomogeneous material and normal or fragmented hair. This dot is thought to represent the initial microscopic sign of direct toxicity of chemotherapy on the hair follicle. Chemotherapy-induced alopecia dots persist throughout chemotherapy and subsequently disappear after chemotherapy ends.²⁷

Limitations and Advantages—Currently, subtypes of cicatricial alopecias cannot be characterized on RCM because inflammatory cell types are not distinguished from each other (eg, eosinophils vs neutrophils). Another limitation of RCM is the loss of resolution below the superficial papillary dermis (a depth of approximately 150 µm); thus, deeper structures, such as the hair bulb, cannot be visualized.

Unlike global photography and trichoscopy, which are low-cost methods, RCM is much more costly, ranging upwards of several thousand dollars, and it may require additional technical support fees, making it less accessible for clinical practice. However, RCM imaging continues to be recommended as an intermediate step between trichoscopy and histology for the diagnosis and management of hair disease.²⁶ If a biopsy is required, RCM can aid in the selection of a biopsy site, as areas with active inflammation are more informative than atrophic and fibrosed areas.²³ The role of RCM in trichoscopy can be expanded by designing a more cost-effective and ergonomically suited scope for hair and scalp assessment.

Optical Coherence Tomography

Optical coherence tomography is a noninvasive handheld device that emits low-power infrared light to visualize the skin and adnexal structures. Optical coherence tomography relies on the principle of interferometry to detect phase differences in optical backscattering at varying tissue depths.^28,29 It allows visualization up to 2 mm, which is 2 to 5 times deeper than RCM.³⁶ Unlike RCM, which has cellular resolution, OCT has an axial resolution of 3 to 15 μm, which allows only for the detection of structural boundaries.³⁰ There are various OCT modalities that differ in lateral and axial resolutions and maximum depth. Commercial software is available that measures changes in vascular density by depth, epidermal thickness, skin surface texture, and optical attenuation—the latter being an indirect measurement of collagen density and skin hydration.

Structures Visualized—Hair follicles can be well distinguished on OCT images, and as such, OCT is recognized as a diagnostic tool in trichology (Figure 4).³¹ Follicular openings, interfollicular collagen, and outlines of the hair shafts are visible; however, detailed components of the follicular unit cannot be visualized by OCT. Keratin hyperrefractivity identifies the hair shaft. Additionally, the hair matrix is denoted by a slightly granular texture in the dermis. Dynamic OCT produces colorized images that visualize blood flow within vessels.

Applications of OCT—Optical coherence tomography is utilized in investigative trichology because it provides highly reproducible measurements of hair shaft diameters, cross-sectional surface areas, and form factor, which is a surrogate parameter for hair shape. The cross-section of hair shafts provides insight into local metabolism and perifollicular inflammation. Cross-sections of hair shafts in areas of alopecia areata were found to be smaller than cross-sections in the unaffected scalp within the same individual.³² Follicular density can be manually quantified on OCT images, but there also is promise for automated quantification. A recent study by Urban et al³³ described training a convolutional neural network to automatically count hair as well as hair-bearing and non–hair-bearing follicles in OCT scans. These investigators also were able to color-code hair according to height, resulting in the creation of a “height” map.

Optical coherence tomography has furthered our understanding of the pathophysiology of cicatricial and nonscarring alopecias. Vazquez-Herrera et al³⁴ assessed the inflammatory and cicatricial stages of frontal fibrosing alopecia by OCT imaging. Inflammatory hairlines, which are seen in the early stages of frontal fibrosing alopecia, exhibited a thickened dermis, irregular distribution of collagen, and increased vascularity in both the superficial and deep dermal layers compared to cicatricial and healthy scalp. Conversely, late-stage cicatricial areas exhibited a thin dermis and collagen that appeared in a hyperreflective, concentric, onion-shaped pattern around remnant follicular openings. Vascular flow was reduced in the superficial dermis of a cicatricial scalp but increased in the deep dermal layers compared with a healthy scalp. The attenuation coefficients of these disease stages also were assessed. The attenuation coefficient of the inflammatory hairline was higher compared with normal skin, likely as a reflection of inflammatory infiltrate and edema, whereas the attenuation coefficient of cicatricial scalp was lower compared with normal skin, likely reflecting the reduced water content of atrophic skin.³⁴ This differentiation of early- and late-stage cicatricial alopecias has implications for early treatment and improved prognosis. Additionally, there is potential for OCT to assist in the differentiation of alopecia subtypes, as it can measure the epidermal thickness and follicular density and was previously used to compare scarring and nonscarring alopecia.³⁵

Advantages and Limitations—Similar to RCM, OCT may be cost prohibitive for some clinicians. In addition, OCT cannot visualize the follicular unit in cellular detail. However, the extent of OCT’s capabilities may not be fully realized. Dynamic OCT is a new angiographic type of OCT that shows potential in monitoring early subclinical responses to novel alopecia therapies, such as platelet-rich plasminogen, which is hypothesized to stimulate hair growth through angiogenesis. Additionally, OCT may improve outcomes of hair transplantation procedures by allowing for visualization of the subcutaneous angle of hair follicles. Blind extraction of hair follicles in follicular unit extraction procedures can result in inadvertent transection and damage to the hair follicle; OCT could help identify good candidates for follicular unit extraction, such as patients with hair follicles in parallel arrangement, who are predicted to have better results.³⁶

Conclusion

The field of trichology will continue to evolve with the emergence of noninvasive imaging technologies that diagnose hair disease in early stages and enable treatment monitoring with quantification of hair parameters. As discussed in this review, global photography, trichoscopy, RCM, and OCT have furthered our understanding of alopecia pathophysiology and provided objective methods of treatment evaluation. The capabilities of these tools will continue to expand with advancements in add-on software and AI algorithms.

Practice Gap

Wound dressings protect the skin and prevent contamination. The hair often makes it difficult to affix a dressing after a minor scalp trauma or local surgery on the head. Traditional approaches for fastening a dressing on the head include bandage winding or adhesive tape, but these methods often affect aesthetics or cause discomfort—bandage winding can make it inconvenient for the patient to move their head, and adhesive tape can cause pain by pulling the hair during removal.

To better position a scalp dressing, tie-over dressings, braid dressings, and paper clips have been used as fixators.^1-3 These methods have benefits and disadvantages.

Tie-over Dressing—The dressing is clasped with long sutures that were reserved during wound closure. This method is sturdy, can slightly compress the wound, and is applicable to any part of the scalp. However, it requires more sutures, and more careful wound care may be required due to the edge of the dressing being close to the wound.

Braid Dressing—Tape, a rubber band, or braided hair is used to bind the gauze pad. This dressing is simple and inexpensive. However, it is limited to patients with long hair; even then, it often is difficult to anchor the dressing by braiding hair. Moreover, removal of the rubber band and tape can cause discomfort or pain.

Paper Clip—This is a simple scalp dressing fixator. However, due to the short and circular structure of the clip, it is not conducive to affixing a gauze dressing for patients with short hair, and it often hooks the gauze and hair, making it inconvenient for the physician and a source of discomfort for the patient when the paper clip is being removed.

The Technique

To address shortcomings of traditional methods, we encourage the use of hairpins to affix a dressing after a scalp wound is sutured. Two steps are required:

• Position the gauze to cover the wound and press the gauze down with your hand.
• Clamp the 4 corners of the dressing and adjacent hair with hairpins (Figure, A).

Practical Implications

Hairpins are common for fixing hairstyles and decorating hair. They are inexpensive, easy to obtain, simple in structure, convenient to use without additional discomfort, and easy to remove (Figure, B). Because most hairpins have a powerful clamping force, they can affix dressings in short hair (Figure, A). All medical staff can use hairpins to anchor the scalp dressing. Even a patient’s family members can carry out simple dressing replacement and wound cleaning using this method. Patients also have many options for hairpin styles, which is especially useful in easing the apprehension of surgery in pediatric patients.

Practice Gap

Wound dressings protect the skin and prevent contamination. The hair often makes it difficult to affix a dressing after a minor scalp trauma or local surgery on the head. Traditional approaches for fastening a dressing on the head include bandage winding or adhesive tape, but these methods often affect aesthetics or cause discomfort—bandage winding can make it inconvenient for the patient to move their head, and adhesive tape can cause pain by pulling the hair during removal.

To better position a scalp dressing, tie-over dressings, braid dressings, and paper clips have been used as fixators.^1-3 These methods have benefits and disadvantages.

Tie-over Dressing—The dressing is clasped with long sutures that were reserved during wound closure. This method is sturdy, can slightly compress the wound, and is applicable to any part of the scalp. However, it requires more sutures, and more careful wound care may be required due to the edge of the dressing being close to the wound.

Braid Dressing—Tape, a rubber band, or braided hair is used to bind the gauze pad. This dressing is simple and inexpensive. However, it is limited to patients with long hair; even then, it often is difficult to anchor the dressing by braiding hair. Moreover, removal of the rubber band and tape can cause discomfort or pain.

Paper Clip—This is a simple scalp dressing fixator. However, due to the short and circular structure of the clip, it is not conducive to affixing a gauze dressing for patients with short hair, and it often hooks the gauze and hair, making it inconvenient for the physician and a source of discomfort for the patient when the paper clip is being removed.

The Technique

To address shortcomings of traditional methods, we encourage the use of hairpins to affix a dressing after a scalp wound is sutured. Two steps are required:

• Position the gauze to cover the wound and press the gauze down with your hand.
• Clamp the 4 corners of the dressing and adjacent hair with hairpins (Figure, A).

Practical Implications

Hairpins are common for fixing hairstyles and decorating hair. They are inexpensive, easy to obtain, simple in structure, convenient to use without additional discomfort, and easy to remove (Figure, B). Because most hairpins have a powerful clamping force, they can affix dressings in short hair (Figure, A). All medical staff can use hairpins to anchor the scalp dressing. Even a patient’s family members can carry out simple dressing replacement and wound cleaning using this method. Patients also have many options for hairpin styles, which is especially useful in easing the apprehension of surgery in pediatric patients.

Practice Gap

Wound dressings protect the skin and prevent contamination. The hair often makes it difficult to affix a dressing after a minor scalp trauma or local surgery on the head. Traditional approaches for fastening a dressing on the head include bandage winding or adhesive tape, but these methods often affect aesthetics or cause discomfort—bandage winding can make it inconvenient for the patient to move their head, and adhesive tape can cause pain by pulling the hair during removal.

To better position a scalp dressing, tie-over dressings, braid dressings, and paper clips have been used as fixators.^1-3 These methods have benefits and disadvantages.

Tie-over Dressing—The dressing is clasped with long sutures that were reserved during wound closure. This method is sturdy, can slightly compress the wound, and is applicable to any part of the scalp. However, it requires more sutures, and more careful wound care may be required due to the edge of the dressing being close to the wound.

Braid Dressing—Tape, a rubber band, or braided hair is used to bind the gauze pad. This dressing is simple and inexpensive. However, it is limited to patients with long hair; even then, it often is difficult to anchor the dressing by braiding hair. Moreover, removal of the rubber band and tape can cause discomfort or pain.

Paper Clip—This is a simple scalp dressing fixator. However, due to the short and circular structure of the clip, it is not conducive to affixing a gauze dressing for patients with short hair, and it often hooks the gauze and hair, making it inconvenient for the physician and a source of discomfort for the patient when the paper clip is being removed.

The Technique

To address shortcomings of traditional methods, we encourage the use of hairpins to affix a dressing after a scalp wound is sutured. Two steps are required:

• Position the gauze to cover the wound and press the gauze down with your hand.
• Clamp the 4 corners of the dressing and adjacent hair with hairpins (Figure, A).

Practical Implications

Hairpins are common for fixing hairstyles and decorating hair. They are inexpensive, easy to obtain, simple in structure, convenient to use without additional discomfort, and easy to remove (Figure, B). Because most hairpins have a powerful clamping force, they can affix dressings in short hair (Figure, A). All medical staff can use hairpins to anchor the scalp dressing. Even a patient’s family members can carry out simple dressing replacement and wound cleaning using this method. Patients also have many options for hairpin styles, which is especially useful in easing the apprehension of surgery in pediatric patients.