Article

Case Presentation

A 55-year-old White male Gulf War Marine veteran with a history of irritable bowel syndrome, chronic low back pain, anxiety, posttraumatic stress disorder (PTSD), and a 35 pack-year smoking history presented to the Edward Hines, Jr. Veterans Affairs Hospital primary care clinic with moderate abdominal pain for 1 week and altered bowel habits for several months. He reported mainly having diarrhea and more bloating than usual. The patient stated that he had experienced progressive fatigue over the past 6 months, along with new drenching night sweats and chills. He reported a 20-lb unintentional weight loss over the past 6 months. The patient noted no substance use or changes to his diet or exercise pattern. He had previously served in the US Marine Corps and was deployed to Okinawa, Camp Lejeune, Iraq, and Honduras during his 10-year military career.

This patient’s initial abdominal computed tomography (CT) revealed multiple prominent lymph nodes in the peripancreatic, periportal, retroperitoneal, bilateral iliac, and inguinal regions. Due to substantial lymphadenopathy and gastrointestinal complaints, he was evaluated by gastroenterology and underwent both esophagogastroduodenoscopy and colonoscopy. Results were notable for gastric mucosal inflammation and intestinal metaplasia, as well as tubular adenomas throughout the colon; however, there was no evidence of mass lesions.

Due to ongoing systemic symptoms of unknown etiology, the patient underwent CT of the chest, revealing a 2.3-cm right lower lobe (RLL) pulmonary mass with right hilar lymphadenopathy. A positron emission tomography (PET) demonstrated hypermetabolic activity in the RLL nodule (standardized uptake value [SUV], 3.1) and adjacent lymph nodes (SUV, ≤ 5.8).

The patient was told that he likely had metastatic disease and was referred to the Hematology-Oncology service. He reported increased anxiety and insomnia. He also was referred to the Mental Health service, which started him on escitalopram 10 mg daily and hydroxyzine 25 mg daily as needed, and recommended therapy.

The Pulmonology service performed an endobronchial ultrasound (EBUS)-guided biopsy of mediastinal lymph nodes and the RLL nodule. Pathologic examination yielded necrotic debris and benign lymphoid tissue. All cultures and stains for fungal, mycobacterial, and bacterial organisms were negative.

The patient then underwent thoracic surgery for diagnostic wedge resection of the RLL. Histopathology revealed necrotizing granulomatous inflammation with fungal organisms morphologically consistent with Histoplasma. All microbiologic cultures remained negative. The patient’s urine and serum histoplasma antigen, serum cryptococcal antigen, β-D-glucan, QuantiFERON-TB Gold, and blastomycosis tests were negative. The patient started itraconazole 200 mg twice daily and experienced slow improvements in his symptoms with follow-up by the Infectious Disease service and decreased anxiety.

Discussion

This case highlights the diagnostic challenges associated with disseminated fungal infections, namely histoplasmosis, which can closely mimic malignancy in both clinical presentation and imaging.^1-3 The patient presented with classic B symptoms, diffuse lymphadenopathy, and a suspicious lung nodule, all features highly suggestive of malignancy.

Classic “B symptoms” (eg, fever, drenching night sweats, and unintentional weight loss) are constitutional manifestations that occur in association with lymphoid malignancies, particularly Hodgkin lymphoma and certain non-Hodgkin lymphomas. Their presence is central to disease staging, prognosis, and therapeutic decision-making.⁴ The Ann Arbor staging system classifies systemic symptoms as B symptoms when any of the following are present: fever > 38 °C in the absence of infection, often intermittent; drenching night sweats requiring a change of bedclothes or sheets; or unintentional weight loss of > 10% of baseline body weight over 6 months.⁵

Although often associated with lymphomas, B symptoms are not pathognomonic. They may occur in chronic infections, such as tuberculosis and HIV infection, autoimmune diseases, and solid tumors.^5,6 Thorough evaluation, including infectious and inflammatory workups, is essential before attributing these systemic manifestations to a neoplasm.

Histoplasma capsulatum, the causative agent of histoplasmosis, is endemic in certain parts of the United States, including the Ohio and Mississippi River valleys. However, the fungus is also found in the Middle East, Asia, Africa, and Central and South America.⁷ It is acquired via inhalation of soil contaminated with bird or bat droppings.¹ The patient’s military service represents a potential environmental exposure risk. While immunocompetent individuals typically clear the infection, chronic progressive disseminated histoplasmosis can develop, particularly in patients with underlying pulmonary disease or subtle immunosuppression. ^1,8

Negative fungal serologies and antigen tests, as seen in this patient, are not uncommon in subacute or localized disease and should not delay further diagnostic interventions when clinical suspicion remains high.^2,9 Invasive procedures, including wedge resection, may be required to establish a definitive diagnosis.

EBUS-guided transbronchial needle aspiration (EBUS-TBNA) is a valuable minimally invasive technique for the evaluation of mediastinal and hilar lymphadenopathy. However, its diagnostic performance in cases of histoplasmosis is limited by several factors. First, low organism burden is a significant limitation. In immunocompetent individuals with subacute pulmonary histoplasmosis, the fungal load within lymph nodes or pulmonary tissue is often low, leading to negative fungal cultures specimens obtained using EBUS.¹⁰ Second, the diagnostic yield of EBUS-TBNA for identifying Histoplasma capsulatum is variable. Detection of fungal elements or successful culture may be inconsistent and is influenced by operator expertise, needle size, number of passes, and specimen handling and processing techniques. Third, overlapping cytopathologic findings can complicate interpretation. The granulomatous inflammation characteristic of histoplasmosis is nonspecific and may also be observed in other conditions such as tuberculosis, sarcoidosis, and certain lymphoproliferative disorders. Therefore, clinical and radiologic correlation, as well as adjunctive testing, are essential for accurate diagnosis. ¹¹ Fourth, sample quality poses additional challenges. Differentiating inflammatory cells from neoplastic elements, managing poorly preserved specimens, and avoiding contamination from bronchial wall tissue can all affect diagnostic accuracy.¹² Finally, inadequate or nondiagnostic sampling occurs in a subset of patients. Case series have reported nondiagnostic EBUS-TBNA results, necessitating reliance on complementary diagnostic modalities, including serologic assays, urine antigen testing, or surgical biopsy, to establish a definitive diagnosis.⁹

Necrotizing granulomas without confirmed microbiologic identification may still justify antifungal treatment if histopathologic findings are consistent with fungal infection, as in this patient.^1,3 Itraconazole remains the first-line treatment, though adverse effects and treatment duration may impact adherence.³

The presentation of pulmonary nodules and diffuse lymphadenopathy in this patient was strongly suggestive of metastatic disease, especially given his smoking history. However, histoplasmosis can closely mimic metastatic cancer radiographically, leading to potential misdiagnosis.¹³ In endemic areas, histoplasmosis should be included in the differential for any patient with suspicious thoracic imaging.

In this case, the diagnosis of malignancy was prematurely communicated to the patient based solely on imaging, prior to histologic confirmation. This approach carries significant risk, including psychological distress, initiation of inappropriate treatments, and delayed antifungal therapy. A similar diagnostic dilemma was described by Wheat et al, who emphasized the need for tissue sampling in distinguishing fungal infections from malignancy.¹⁴ In the absence of tissue diagnosis, reliance on radiologic criteria alone can be misleading. PETs, which detect metabolic activity, are not specific and can show uptake in both neoplastic and inflammatory processes.¹⁵

This case reinforces the principle of diagnostic humility: no diagnosis, especially one as consequential as cancer, should be confirmed without histologic or microbiologic evidence. Multidisciplinary evaluation and appropriate use of tissue sampling are crucial to avoid harmful diagnostic errors.

Conclusions

In patients presenting with constitutional symptoms, diffuse lymphadenopathy, and pulmonary nodules, disseminated fungal infections such as histoplasmosis must remain in the differential diagnosis, even in the absence of positive fungal serologies.^1,2 Tissue diagnosis through invasive procedures may be necessary, particularly when initial biopsies and cultures are inconclusive. ¹ Early recognition and treatment are critical to avoid complications from progressive disseminated infection.^3,8

Case Presentation

A 55-year-old White male Gulf War Marine veteran with a history of irritable bowel syndrome, chronic low back pain, anxiety, posttraumatic stress disorder (PTSD), and a 35 pack-year smoking history presented to the Edward Hines, Jr. Veterans Affairs Hospital primary care clinic with moderate abdominal pain for 1 week and altered bowel habits for several months. He reported mainly having diarrhea and more bloating than usual. The patient stated that he had experienced progressive fatigue over the past 6 months, along with new drenching night sweats and chills. He reported a 20-lb unintentional weight loss over the past 6 months. The patient noted no substance use or changes to his diet or exercise pattern. He had previously served in the US Marine Corps and was deployed to Okinawa, Camp Lejeune, Iraq, and Honduras during his 10-year military career.

This patient’s initial abdominal computed tomography (CT) revealed multiple prominent lymph nodes in the peripancreatic, periportal, retroperitoneal, bilateral iliac, and inguinal regions. Due to substantial lymphadenopathy and gastrointestinal complaints, he was evaluated by gastroenterology and underwent both esophagogastroduodenoscopy and colonoscopy. Results were notable for gastric mucosal inflammation and intestinal metaplasia, as well as tubular adenomas throughout the colon; however, there was no evidence of mass lesions.

Due to ongoing systemic symptoms of unknown etiology, the patient underwent CT of the chest, revealing a 2.3-cm right lower lobe (RLL) pulmonary mass with right hilar lymphadenopathy. A positron emission tomography (PET) demonstrated hypermetabolic activity in the RLL nodule (standardized uptake value [SUV], 3.1) and adjacent lymph nodes (SUV, ≤ 5.8).

The patient was told that he likely had metastatic disease and was referred to the Hematology-Oncology service. He reported increased anxiety and insomnia. He also was referred to the Mental Health service, which started him on escitalopram 10 mg daily and hydroxyzine 25 mg daily as needed, and recommended therapy.

The Pulmonology service performed an endobronchial ultrasound (EBUS)-guided biopsy of mediastinal lymph nodes and the RLL nodule. Pathologic examination yielded necrotic debris and benign lymphoid tissue. All cultures and stains for fungal, mycobacterial, and bacterial organisms were negative.

The patient then underwent thoracic surgery for diagnostic wedge resection of the RLL. Histopathology revealed necrotizing granulomatous inflammation with fungal organisms morphologically consistent with Histoplasma. All microbiologic cultures remained negative. The patient’s urine and serum histoplasma antigen, serum cryptococcal antigen, β-D-glucan, QuantiFERON-TB Gold, and blastomycosis tests were negative. The patient started itraconazole 200 mg twice daily and experienced slow improvements in his symptoms with follow-up by the Infectious Disease service and decreased anxiety.

Discussion

This case highlights the diagnostic challenges associated with disseminated fungal infections, namely histoplasmosis, which can closely mimic malignancy in both clinical presentation and imaging.^1-3 The patient presented with classic B symptoms, diffuse lymphadenopathy, and a suspicious lung nodule, all features highly suggestive of malignancy.

Classic “B symptoms” (eg, fever, drenching night sweats, and unintentional weight loss) are constitutional manifestations that occur in association with lymphoid malignancies, particularly Hodgkin lymphoma and certain non-Hodgkin lymphomas. Their presence is central to disease staging, prognosis, and therapeutic decision-making.⁴ The Ann Arbor staging system classifies systemic symptoms as B symptoms when any of the following are present: fever > 38 °C in the absence of infection, often intermittent; drenching night sweats requiring a change of bedclothes or sheets; or unintentional weight loss of > 10% of baseline body weight over 6 months.⁵

Although often associated with lymphomas, B symptoms are not pathognomonic. They may occur in chronic infections, such as tuberculosis and HIV infection, autoimmune diseases, and solid tumors.^5,6 Thorough evaluation, including infectious and inflammatory workups, is essential before attributing these systemic manifestations to a neoplasm.

Histoplasma capsulatum, the causative agent of histoplasmosis, is endemic in certain parts of the United States, including the Ohio and Mississippi River valleys. However, the fungus is also found in the Middle East, Asia, Africa, and Central and South America.⁷ It is acquired via inhalation of soil contaminated with bird or bat droppings.¹ The patient’s military service represents a potential environmental exposure risk. While immunocompetent individuals typically clear the infection, chronic progressive disseminated histoplasmosis can develop, particularly in patients with underlying pulmonary disease or subtle immunosuppression. ^1,8

Negative fungal serologies and antigen tests, as seen in this patient, are not uncommon in subacute or localized disease and should not delay further diagnostic interventions when clinical suspicion remains high.^2,9 Invasive procedures, including wedge resection, may be required to establish a definitive diagnosis.

EBUS-guided transbronchial needle aspiration (EBUS-TBNA) is a valuable minimally invasive technique for the evaluation of mediastinal and hilar lymphadenopathy. However, its diagnostic performance in cases of histoplasmosis is limited by several factors. First, low organism burden is a significant limitation. In immunocompetent individuals with subacute pulmonary histoplasmosis, the fungal load within lymph nodes or pulmonary tissue is often low, leading to negative fungal cultures specimens obtained using EBUS.¹⁰ Second, the diagnostic yield of EBUS-TBNA for identifying Histoplasma capsulatum is variable. Detection of fungal elements or successful culture may be inconsistent and is influenced by operator expertise, needle size, number of passes, and specimen handling and processing techniques. Third, overlapping cytopathologic findings can complicate interpretation. The granulomatous inflammation characteristic of histoplasmosis is nonspecific and may also be observed in other conditions such as tuberculosis, sarcoidosis, and certain lymphoproliferative disorders. Therefore, clinical and radiologic correlation, as well as adjunctive testing, are essential for accurate diagnosis. ¹¹ Fourth, sample quality poses additional challenges. Differentiating inflammatory cells from neoplastic elements, managing poorly preserved specimens, and avoiding contamination from bronchial wall tissue can all affect diagnostic accuracy.¹² Finally, inadequate or nondiagnostic sampling occurs in a subset of patients. Case series have reported nondiagnostic EBUS-TBNA results, necessitating reliance on complementary diagnostic modalities, including serologic assays, urine antigen testing, or surgical biopsy, to establish a definitive diagnosis.⁹

Necrotizing granulomas without confirmed microbiologic identification may still justify antifungal treatment if histopathologic findings are consistent with fungal infection, as in this patient.^1,3 Itraconazole remains the first-line treatment, though adverse effects and treatment duration may impact adherence.³

The presentation of pulmonary nodules and diffuse lymphadenopathy in this patient was strongly suggestive of metastatic disease, especially given his smoking history. However, histoplasmosis can closely mimic metastatic cancer radiographically, leading to potential misdiagnosis.¹³ In endemic areas, histoplasmosis should be included in the differential for any patient with suspicious thoracic imaging.

In this case, the diagnosis of malignancy was prematurely communicated to the patient based solely on imaging, prior to histologic confirmation. This approach carries significant risk, including psychological distress, initiation of inappropriate treatments, and delayed antifungal therapy. A similar diagnostic dilemma was described by Wheat et al, who emphasized the need for tissue sampling in distinguishing fungal infections from malignancy.¹⁴ In the absence of tissue diagnosis, reliance on radiologic criteria alone can be misleading. PETs, which detect metabolic activity, are not specific and can show uptake in both neoplastic and inflammatory processes.¹⁵

This case reinforces the principle of diagnostic humility: no diagnosis, especially one as consequential as cancer, should be confirmed without histologic or microbiologic evidence. Multidisciplinary evaluation and appropriate use of tissue sampling are crucial to avoid harmful diagnostic errors.

Conclusions

In patients presenting with constitutional symptoms, diffuse lymphadenopathy, and pulmonary nodules, disseminated fungal infections such as histoplasmosis must remain in the differential diagnosis, even in the absence of positive fungal serologies.^1,2 Tissue diagnosis through invasive procedures may be necessary, particularly when initial biopsies and cultures are inconclusive. ¹ Early recognition and treatment are critical to avoid complications from progressive disseminated infection.^3,8

Case Presentation

A 55-year-old White male Gulf War Marine veteran with a history of irritable bowel syndrome, chronic low back pain, anxiety, posttraumatic stress disorder (PTSD), and a 35 pack-year smoking history presented to the Edward Hines, Jr. Veterans Affairs Hospital primary care clinic with moderate abdominal pain for 1 week and altered bowel habits for several months. He reported mainly having diarrhea and more bloating than usual. The patient stated that he had experienced progressive fatigue over the past 6 months, along with new drenching night sweats and chills. He reported a 20-lb unintentional weight loss over the past 6 months. The patient noted no substance use or changes to his diet or exercise pattern. He had previously served in the US Marine Corps and was deployed to Okinawa, Camp Lejeune, Iraq, and Honduras during his 10-year military career.

This patient’s initial abdominal computed tomography (CT) revealed multiple prominent lymph nodes in the peripancreatic, periportal, retroperitoneal, bilateral iliac, and inguinal regions. Due to substantial lymphadenopathy and gastrointestinal complaints, he was evaluated by gastroenterology and underwent both esophagogastroduodenoscopy and colonoscopy. Results were notable for gastric mucosal inflammation and intestinal metaplasia, as well as tubular adenomas throughout the colon; however, there was no evidence of mass lesions.

Due to ongoing systemic symptoms of unknown etiology, the patient underwent CT of the chest, revealing a 2.3-cm right lower lobe (RLL) pulmonary mass with right hilar lymphadenopathy. A positron emission tomography (PET) demonstrated hypermetabolic activity in the RLL nodule (standardized uptake value [SUV], 3.1) and adjacent lymph nodes (SUV, ≤ 5.8).

The patient was told that he likely had metastatic disease and was referred to the Hematology-Oncology service. He reported increased anxiety and insomnia. He also was referred to the Mental Health service, which started him on escitalopram 10 mg daily and hydroxyzine 25 mg daily as needed, and recommended therapy.

The Pulmonology service performed an endobronchial ultrasound (EBUS)-guided biopsy of mediastinal lymph nodes and the RLL nodule. Pathologic examination yielded necrotic debris and benign lymphoid tissue. All cultures and stains for fungal, mycobacterial, and bacterial organisms were negative.

The patient then underwent thoracic surgery for diagnostic wedge resection of the RLL. Histopathology revealed necrotizing granulomatous inflammation with fungal organisms morphologically consistent with Histoplasma. All microbiologic cultures remained negative. The patient’s urine and serum histoplasma antigen, serum cryptococcal antigen, β-D-glucan, QuantiFERON-TB Gold, and blastomycosis tests were negative. The patient started itraconazole 200 mg twice daily and experienced slow improvements in his symptoms with follow-up by the Infectious Disease service and decreased anxiety.

Discussion

This case highlights the diagnostic challenges associated with disseminated fungal infections, namely histoplasmosis, which can closely mimic malignancy in both clinical presentation and imaging.^1-3 The patient presented with classic B symptoms, diffuse lymphadenopathy, and a suspicious lung nodule, all features highly suggestive of malignancy.

Classic “B symptoms” (eg, fever, drenching night sweats, and unintentional weight loss) are constitutional manifestations that occur in association with lymphoid malignancies, particularly Hodgkin lymphoma and certain non-Hodgkin lymphomas. Their presence is central to disease staging, prognosis, and therapeutic decision-making.⁴ The Ann Arbor staging system classifies systemic symptoms as B symptoms when any of the following are present: fever > 38 °C in the absence of infection, often intermittent; drenching night sweats requiring a change of bedclothes or sheets; or unintentional weight loss of > 10% of baseline body weight over 6 months.⁵

Although often associated with lymphomas, B symptoms are not pathognomonic. They may occur in chronic infections, such as tuberculosis and HIV infection, autoimmune diseases, and solid tumors.^5,6 Thorough evaluation, including infectious and inflammatory workups, is essential before attributing these systemic manifestations to a neoplasm.

Histoplasma capsulatum, the causative agent of histoplasmosis, is endemic in certain parts of the United States, including the Ohio and Mississippi River valleys. However, the fungus is also found in the Middle East, Asia, Africa, and Central and South America.⁷ It is acquired via inhalation of soil contaminated with bird or bat droppings.¹ The patient’s military service represents a potential environmental exposure risk. While immunocompetent individuals typically clear the infection, chronic progressive disseminated histoplasmosis can develop, particularly in patients with underlying pulmonary disease or subtle immunosuppression. ^1,8

Negative fungal serologies and antigen tests, as seen in this patient, are not uncommon in subacute or localized disease and should not delay further diagnostic interventions when clinical suspicion remains high.^2,9 Invasive procedures, including wedge resection, may be required to establish a definitive diagnosis.

EBUS-guided transbronchial needle aspiration (EBUS-TBNA) is a valuable minimally invasive technique for the evaluation of mediastinal and hilar lymphadenopathy. However, its diagnostic performance in cases of histoplasmosis is limited by several factors. First, low organism burden is a significant limitation. In immunocompetent individuals with subacute pulmonary histoplasmosis, the fungal load within lymph nodes or pulmonary tissue is often low, leading to negative fungal cultures specimens obtained using EBUS.¹⁰ Second, the diagnostic yield of EBUS-TBNA for identifying Histoplasma capsulatum is variable. Detection of fungal elements or successful culture may be inconsistent and is influenced by operator expertise, needle size, number of passes, and specimen handling and processing techniques. Third, overlapping cytopathologic findings can complicate interpretation. The granulomatous inflammation characteristic of histoplasmosis is nonspecific and may also be observed in other conditions such as tuberculosis, sarcoidosis, and certain lymphoproliferative disorders. Therefore, clinical and radiologic correlation, as well as adjunctive testing, are essential for accurate diagnosis. ¹¹ Fourth, sample quality poses additional challenges. Differentiating inflammatory cells from neoplastic elements, managing poorly preserved specimens, and avoiding contamination from bronchial wall tissue can all affect diagnostic accuracy.¹² Finally, inadequate or nondiagnostic sampling occurs in a subset of patients. Case series have reported nondiagnostic EBUS-TBNA results, necessitating reliance on complementary diagnostic modalities, including serologic assays, urine antigen testing, or surgical biopsy, to establish a definitive diagnosis.⁹

Necrotizing granulomas without confirmed microbiologic identification may still justify antifungal treatment if histopathologic findings are consistent with fungal infection, as in this patient.^1,3 Itraconazole remains the first-line treatment, though adverse effects and treatment duration may impact adherence.³

The presentation of pulmonary nodules and diffuse lymphadenopathy in this patient was strongly suggestive of metastatic disease, especially given his smoking history. However, histoplasmosis can closely mimic metastatic cancer radiographically, leading to potential misdiagnosis.¹³ In endemic areas, histoplasmosis should be included in the differential for any patient with suspicious thoracic imaging.

In this case, the diagnosis of malignancy was prematurely communicated to the patient based solely on imaging, prior to histologic confirmation. This approach carries significant risk, including psychological distress, initiation of inappropriate treatments, and delayed antifungal therapy. A similar diagnostic dilemma was described by Wheat et al, who emphasized the need for tissue sampling in distinguishing fungal infections from malignancy.¹⁴ In the absence of tissue diagnosis, reliance on radiologic criteria alone can be misleading. PETs, which detect metabolic activity, are not specific and can show uptake in both neoplastic and inflammatory processes.¹⁵

This case reinforces the principle of diagnostic humility: no diagnosis, especially one as consequential as cancer, should be confirmed without histologic or microbiologic evidence. Multidisciplinary evaluation and appropriate use of tissue sampling are crucial to avoid harmful diagnostic errors.

Conclusions

In patients presenting with constitutional symptoms, diffuse lymphadenopathy, and pulmonary nodules, disseminated fungal infections such as histoplasmosis must remain in the differential diagnosis, even in the absence of positive fungal serologies.^1,2 Tissue diagnosis through invasive procedures may be necessary, particularly when initial biopsies and cultures are inconclusive. ¹ Early recognition and treatment are critical to avoid complications from progressive disseminated infection.^3,8

Randomized Trial Supports Sirolimus as Add-On Systemic Lupus Erythematosus Therapy

Adding sirolimus to standard treatment for active systemic lupus erythematosus improved disease control compared with placebo in a randomized phase 3 trial presented at the European Alliance of Associations for Rheumatology (EULAR) 2026 Annual Meeting. Patients receiving sirolimus were more likely to achieve a clinical response and showed greater improvement in disease activity and serologic markers. Treatment generally was well tolerated, although lipid abnormalities, leukopenia, and menstrual irregularities were more common. Sirolimus may become a useful oral option for refractory lupus, pending further confirmation and guidance.

Bimekizumab Trumps Risankizumab in Head-to-Head Psoriatic Arthritis Trial

Dual IL-17 blockade may offer greater joint benefit than IL-23 inhibition in psoriatic arthritis, potentially helping guide biologic selection for patients with skin and musculoskeletal disease. In the phase 3b BE BOLD trial, bimekizumab was more effective than risankizumab for joint disease, with more patients achieving a 50% improvement in American College of Rheumatology response criteria at 16 weeks. Bimekizumab also showed superior results across several secondary measures, including minimal disease activity and skin outcomes, while safety was broadly similar. The findings were presented at the EULAR 2026 Annual Meeting.

FDA Delays iPLEDGE Modifications Until November 2026

In a June 16 announcement, the US Food and Drug Administration said long-awaited modifications to the iPLEDGE Risk Evaluation and Mitigation Strategy program for isotretinoin—originally set to take effect on August 8, 2026—will be delayed until November 15, 2026. The agency said the extra time will allow testing of the system updates, reduce technical problems, and help avoid interruptions in patient access to isotretinoin. The planned changes are intended to reduce burdens on patients, prescribers, and pharmacies while maintaining safety, and they include allowing at-home pregnancy testing in some cases. Until the new date, the Food and Drug Administration will continue enforcement discretion for pregnancy testing requirements. The update also clarifies that monthly counseling documentation for patients who cannot become pregnant will no longer be required and that pharmacy staff training must be completed annually. iPledge work group chair John Barbieri, MD, MBA, told Medscape Medical News, “It’s important to make sure any changes to the program are implemented in a way that is effective…. I would rather it be done sooner than later, but it’s important it be done right.”

Smoking May Lower Sjögren Disease Risk and Mask Pathology

New data presented at EULAR 2026 suggest that smoking may be associated with a lower likelihood of Sjögren disease and milder salivary gland inflammation, although tobacco is harmful in many autoimmune diseases. In a cohort undergoing salivary gland biopsy for sicca symptoms, current smokers were less likely to have Sjögren disease; among those with disease, smokers had less inflammation and fewer advanced germinal centers. The key takeaway is not that smoking is beneficial, but that tobacco exposure may alter disease phenotype and biopsy interpretation, potentially masking severity and affecting diagnosis.

Skin Disorders in Transgender Patients: Treatment Recommendations

Hormonal therapy in transgender patients can substantially affect skin disease patterns, particularly acne, hair loss, melasma, and possibly hidradenitis suppurativa. In transmasculine patients receiving testosterone, acne is the most common dermatologic complaint and often develops early; isotretinoin is most effective, although pregnancy potential must be considered. Testosterone also contributes to androgenetic alopecia, managed with minoxidil and sometimes finasteride. In transfeminine patients, facial hair and melasma are common concerns. Dermatologists should anticipate these effects and provide gender-affirming care with counseling, examination practices, and preventive treatment.

Randomized Trial Supports Sirolimus as Add-On Systemic Lupus Erythematosus Therapy

Adding sirolimus to standard treatment for active systemic lupus erythematosus improved disease control compared with placebo in a randomized phase 3 trial presented at the European Alliance of Associations for Rheumatology (EULAR) 2026 Annual Meeting. Patients receiving sirolimus were more likely to achieve a clinical response and showed greater improvement in disease activity and serologic markers. Treatment generally was well tolerated, although lipid abnormalities, leukopenia, and menstrual irregularities were more common. Sirolimus may become a useful oral option for refractory lupus, pending further confirmation and guidance.

Bimekizumab Trumps Risankizumab in Head-to-Head Psoriatic Arthritis Trial

Dual IL-17 blockade may offer greater joint benefit than IL-23 inhibition in psoriatic arthritis, potentially helping guide biologic selection for patients with skin and musculoskeletal disease. In the phase 3b BE BOLD trial, bimekizumab was more effective than risankizumab for joint disease, with more patients achieving a 50% improvement in American College of Rheumatology response criteria at 16 weeks. Bimekizumab also showed superior results across several secondary measures, including minimal disease activity and skin outcomes, while safety was broadly similar. The findings were presented at the EULAR 2026 Annual Meeting.

FDA Delays iPLEDGE Modifications Until November 2026

In a June 16 announcement, the US Food and Drug Administration said long-awaited modifications to the iPLEDGE Risk Evaluation and Mitigation Strategy program for isotretinoin—originally set to take effect on August 8, 2026—will be delayed until November 15, 2026. The agency said the extra time will allow testing of the system updates, reduce technical problems, and help avoid interruptions in patient access to isotretinoin. The planned changes are intended to reduce burdens on patients, prescribers, and pharmacies while maintaining safety, and they include allowing at-home pregnancy testing in some cases. Until the new date, the Food and Drug Administration will continue enforcement discretion for pregnancy testing requirements. The update also clarifies that monthly counseling documentation for patients who cannot become pregnant will no longer be required and that pharmacy staff training must be completed annually. iPledge work group chair John Barbieri, MD, MBA, told Medscape Medical News, “It’s important to make sure any changes to the program are implemented in a way that is effective…. I would rather it be done sooner than later, but it’s important it be done right.”

Smoking May Lower Sjögren Disease Risk and Mask Pathology

New data presented at EULAR 2026 suggest that smoking may be associated with a lower likelihood of Sjögren disease and milder salivary gland inflammation, although tobacco is harmful in many autoimmune diseases. In a cohort undergoing salivary gland biopsy for sicca symptoms, current smokers were less likely to have Sjögren disease; among those with disease, smokers had less inflammation and fewer advanced germinal centers. The key takeaway is not that smoking is beneficial, but that tobacco exposure may alter disease phenotype and biopsy interpretation, potentially masking severity and affecting diagnosis.

Skin Disorders in Transgender Patients: Treatment Recommendations

Hormonal therapy in transgender patients can substantially affect skin disease patterns, particularly acne, hair loss, melasma, and possibly hidradenitis suppurativa. In transmasculine patients receiving testosterone, acne is the most common dermatologic complaint and often develops early; isotretinoin is most effective, although pregnancy potential must be considered. Testosterone also contributes to androgenetic alopecia, managed with minoxidil and sometimes finasteride. In transfeminine patients, facial hair and melasma are common concerns. Dermatologists should anticipate these effects and provide gender-affirming care with counseling, examination practices, and preventive treatment.

Randomized Trial Supports Sirolimus as Add-On Systemic Lupus Erythematosus Therapy

Adding sirolimus to standard treatment for active systemic lupus erythematosus improved disease control compared with placebo in a randomized phase 3 trial presented at the European Alliance of Associations for Rheumatology (EULAR) 2026 Annual Meeting. Patients receiving sirolimus were more likely to achieve a clinical response and showed greater improvement in disease activity and serologic markers. Treatment generally was well tolerated, although lipid abnormalities, leukopenia, and menstrual irregularities were more common. Sirolimus may become a useful oral option for refractory lupus, pending further confirmation and guidance.

Bimekizumab Trumps Risankizumab in Head-to-Head Psoriatic Arthritis Trial

Dual IL-17 blockade may offer greater joint benefit than IL-23 inhibition in psoriatic arthritis, potentially helping guide biologic selection for patients with skin and musculoskeletal disease. In the phase 3b BE BOLD trial, bimekizumab was more effective than risankizumab for joint disease, with more patients achieving a 50% improvement in American College of Rheumatology response criteria at 16 weeks. Bimekizumab also showed superior results across several secondary measures, including minimal disease activity and skin outcomes, while safety was broadly similar. The findings were presented at the EULAR 2026 Annual Meeting.

FDA Delays iPLEDGE Modifications Until November 2026

In a June 16 announcement, the US Food and Drug Administration said long-awaited modifications to the iPLEDGE Risk Evaluation and Mitigation Strategy program for isotretinoin—originally set to take effect on August 8, 2026—will be delayed until November 15, 2026. The agency said the extra time will allow testing of the system updates, reduce technical problems, and help avoid interruptions in patient access to isotretinoin. The planned changes are intended to reduce burdens on patients, prescribers, and pharmacies while maintaining safety, and they include allowing at-home pregnancy testing in some cases. Until the new date, the Food and Drug Administration will continue enforcement discretion for pregnancy testing requirements. The update also clarifies that monthly counseling documentation for patients who cannot become pregnant will no longer be required and that pharmacy staff training must be completed annually. iPledge work group chair John Barbieri, MD, MBA, told Medscape Medical News, “It’s important to make sure any changes to the program are implemented in a way that is effective…. I would rather it be done sooner than later, but it’s important it be done right.”

Smoking May Lower Sjögren Disease Risk and Mask Pathology

New data presented at EULAR 2026 suggest that smoking may be associated with a lower likelihood of Sjögren disease and milder salivary gland inflammation, although tobacco is harmful in many autoimmune diseases. In a cohort undergoing salivary gland biopsy for sicca symptoms, current smokers were less likely to have Sjögren disease; among those with disease, smokers had less inflammation and fewer advanced germinal centers. The key takeaway is not that smoking is beneficial, but that tobacco exposure may alter disease phenotype and biopsy interpretation, potentially masking severity and affecting diagnosis.

Skin Disorders in Transgender Patients: Treatment Recommendations

Hormonal therapy in transgender patients can substantially affect skin disease patterns, particularly acne, hair loss, melasma, and possibly hidradenitis suppurativa. In transmasculine patients receiving testosterone, acne is the most common dermatologic complaint and often develops early; isotretinoin is most effective, although pregnancy potential must be considered. Testosterone also contributes to androgenetic alopecia, managed with minoxidil and sometimes finasteride. In transfeminine patients, facial hair and melasma are common concerns. Dermatologists should anticipate these effects and provide gender-affirming care with counseling, examination practices, and preventive treatment.

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of lymphoproliferative malignancies originating from T, B, or natural killer (NK) lymphocytes.¹ Compared to Hodgkin lymphomas, NHLs exhibit a broader clinical spectrum and have a poorer prognosis and frequent extranodal involvement, with the skin being the second most frequent extranodal site.² Primary cutaneous lymphomas (PCLs) are NHLs that are first evident on the skin without evidence of extracutaneous disease at diagnosis. They include a heterogeneous group of cutaneous T-cell lymphomas (CTCLs) and cutaneous B-cell lymphomas. Among CTCLs, mycosis fungoides (MF) is the most prevalent subtype, generally following an indolent course. Cutaneous B-cell lymphomas primarily include follicle center lymphoma and diffuse large B-cell lymphoma.^3,4

The clinical behavior and incidence of PCLs vary dramatically between children and adults, suggesting underlying biologic, immunologic, and genetic differences.^5,6 However, there is a notable lack of comparative studies in the literature addressing these variations, limiting a comprehensive understanding of PCLs and hindering the development of tailored therapeutic strategies. The main objective of this study was to evaluate the different clinical characteristics, subtypes, treatment options, and prognosis in PCLs between pediatric and adult populations.^7,8

Methods

This retrospective observational study included pediatric (aged ≤18 years at diagnosis) and adult (aged >18 years at diagnosis) patients with a clinical and histopathologic diagnosis of PCL who were diagnosed and treated at either of 2 tertiary institutions (Dr. Manuel Gea Gonzalez General Hospital or the National Institute of Pediatrics, both in Mexico City, Mexico) between January 1, 1999, and December 31, 2019. The data analysis included demographic and clinical characteristics, type of PCL (according to World Health Organization [WHO]/European Organisation for Research and Treatment of Cancer [EORTC]) classification,^3,4 treatment administered, and outcome. Disease remission was defined as remittance of clinical PCL manifestations for 3 months or more. Disease control was defined as stable clinical manifestations with no change in PCL stage following treatment initiation. Disease progression was defined as worsening clinical manifestations with an increase in PCL stage and/or development of systemic lymphoma. Beyond similarities and differences across age groups, we also analyzed differences by sex. χ² and Mann-Whitney U tests were used to assess differences between groups. Statistical significance was set at P≤.05. Institutional approval was obtained from both tertiary centers.

Results

Our analysis included a total of 158 patients: 54 (34.2%) were children and 104 (65.8%) were adults. Eighty-eight (55.7%) patients were male (eTable 1). The mean (SD) age at diagnosis was 9.5 (1.9) years in children and 49.7 (18) years in adults. Regarding differences between age groups, adult patients had a similar sex distribution, while in children, the majority of patients were male (37/54 [68.5%]; P=.01).

Overall, the most frequent diagnosis was MF, which occurred in 119 (75.3%) patients, and the most common lesions were erythematous plaques, noted in 95 (60.1%) patients. The lower extremities were the most affected body sites, impacting 127 (80.4%) patients, and the most common treatment was phototherapy, used to treat 110 (69.6%) patients. Reported outcomes included disease control in 45 (28.5%) patients and progression in 36 (22.8%) patients; 50 (31.6%) patients were lost to follow-up. Only 15 (9.5%) patients experienced disease remission, and 12 (7.6%) died.

The mean (SD) time between the onset of symptoms and diagnosis was shorter in children than in adults (18.1 [12.6] months vs 66.2 [34.9] months; P<.001). Regarding involved body sites, the head and neck more frequently affected children than adults (40 [74.1%] vs 33 [31.7%]; P<.001), while the upper extremities were more frequently involved in adults than in children (67 [64.4%] vs 45 [83.3%]; P<.001).

There were significant differences in the morphology of lesions and diagnoses. Children most frequently had hypopigmented plaques (25 [46.3%]) and macules (24 [44.4%])(P<.001) associated with MF, and scars (7 [13.0%]), blisters (6 [11.1%]), and edema (8 [14.8%])(P<.001) associated with positive Epstein-Barr virus (EBV) infection. Adults presented more frequently with hyperpigmented macules (19 [18.3%]) and plaques (37 [35.6%]), erythematous plaques (71 [68.3%]), atrophy (36 [34.6%]), and tumors (32 [30.8%])(P<.001). Adults were more often asymptomatic (86.5% vs 38.8%; P<.001).

Subtypes of PCL differed by age group (eTable 2), with MF being more frequent in adults (87 [83.6%] vs 32 [59.2%]; P<.001), while chronic active positive EBV infection (CAEBVI) manifesting as lymphoproliferative disease (LPD) was exclusive to male children (9 [16.6%])(P<.001). Accordingly, we found variations in systemic treatments used: monoclonal antibodies (mAb), thalidomide, intravenous immunoglobulin (IVIg), and hematopoietic stem cell transplantation (HSCT) were used exclusively for treating children (all P<.001). Outcomes were distributed similarly by age group.

The type of PCL, clinical manifestations, and treatment also varied by sex (eTables 2 and 3). Only males had CAEBVI and presented with edema (8 [9.1%] vs 0%; P<.01). Males also had tumors (23 [26.1%] vs 9 [12.9%]; P=.03) and lesions affecting the head and neck (52 [59.1%] vs 21 [30.0%]; P<.001) more frequently than females. Males were more likely than females to report pain (28 [31.8%] vs 13 [18.6%]; P=.05) and receive systemic treatment with thalidomide (11 [12.5%] vs 1 [1.4%]; P<.001) and IVIg (6 [6.8%] vs 0%; P=.02). Only females were diagnosed with primary cutaneous anaplastic large cell lymphoma (PC-ALCL)(4 [5.7%] vs 0%; P=.03) and had genital involvement (4 [5.7%] vs 0%; P=.03). Females were more likely to be asymptomatic (57 [81.4%] vs 54 [61.4%]; P<.001) or report pruritus (46 [65.7%] vs 44 [50%]; P<.001) and receive local treatment with phototherapy (58 [82.9%] vs 52 [59.1%]; P<.001) compared to males. Although distribution of outcomes was similar by sex, we found males were more frequently lost to follow-up (38 [43.2%] vs 12 [17.1%]; P<.001).

We further searched for differences in clinical manifestations according to the PCL subtype in each age group. The most frequent lesions in 32 children with MF were hypopigmented macules (21 [65.6%]; P<.001)(Figure 1). Three of 5 (60%) children with extranodal NK/T-cell lymphoma, nasal type (ENKTCL), had nodules (P=.002). Of 9 children with CAEBVI, 8 (88.9%) had edema (P<.001), ulcers (P<.001), erythematous plaques (P=.007), and hypopigmented plaques (P=.008); 5 (55.6%) children presented with scars (P<.001) and atrophy (P<.001); and 4 (44.4%) children had blisters (P=.005)(Figure 2). The 2 children with EBV-positive mucocutaneous ulcer (EBV-MCU) had crusts (P=.002) and blisters (P=.01).

Of 87 adults with MF, 54 (62%) had scaly lesions (P=.006)(Figure 3). Of 3 adult patients with PC-ALCL, 2 (66.7%) had crusts (P=.04) and ulcers (P=.05). Two of 3 (66.7%) adults with lymphomatoid papulosis (LyP) had erythematous papules (P<.001). All 4 adult patients with ENKTCL (P=.008) and all 5 patients with primary cutaneous diffuse large B-cell lymphoma, leg-type, had tumors (P<.001).

Finally, we found no differences in outcomes according to types of PCL overall or by age group; however, when categorized by sex, we found males with EBV-MCU more frequently had disease progression than females with EBV-MCU (P=.04).

Comment

Primary cutaneous lymphomas were similarly distributed among males and females (55.6% vs 44.3%, respectively). This slight male predominance was similar to other reports in the literature: one US study reported a male-to-female incidence rate ratio of 1.72, indicating a significantly higher incidence in males (P<.001).⁶ Similar trends have been observed in other geographic regions, with reported male-to-female ratios of 1.56 in Greece and 1.35 in Argentina.^9,10 These findings suggest that PCLs are slightly more prevalent in males across different populations; however, when we stratified by age, pediatric cases of PCL were significantly more frequent in males than in females (68.5% vs. 31.4%; P=.01).

Our analysis revealed that the time to diagnosis was significantly longer in adults than in children (66.2 months vs 18.1 months) for all PCLs (P<.001). The most common type of PCL in both age groups was MF, with a notably higher prevalence in adults than in children (87 [83.7%] vs 32 [59.2%]). The prolonged course of MF in adults, often taking years to progress from early to advanced stages (47.0-52.7 months) may contribute to delayed diagnosis.^8,11,12 Additionally, classic lesions of MF (erythematous scaly plaques) may resemble other common dermatologic conditions, further complicating early recognition and treatment in adults more than in children.^11,12 Conversely, more aggressive and rapidly progressing PCL subtypes, including CAEBVI and ENKTCL-NT, were more frequent in children and would likely be diagnosed more promptly because of the acute onset and fast evolution of signs and symptoms.¹³

Mycosis fungoides is the most common CTCL, followed by CD30+ T-cell disorders such as LyP and PC-ALCL.¹⁴ While MF was the predominant subtype in both age groups, similar to previous reports,^6,7 pediatric patients in our study exhibited distinctive features, such as hypopigmented macules and plaques. Hypopigmented lesions may suggest an underlying immunologic mechanism unique to younger patients, specifically children, in contrast to the hyperpigmented or violaceous lesions predominating in adults.⁷ The hypopigmented variant of MF has been reported to be more prevalent in children, similar to our data, accounting for 54.5% of all pediatric MF cases. These hypopigmented lesions typically manifest at an early stage and follow an indolent course.^15,16 Jung et al⁸ conducted a systematic review of children with MF and reported a mean age at diagnosis of 12.2 years, whereas in our cohort, the mean age was 9.5 years. These findings highlight the different clinical manifestations of MF in children, which may aid in early recognition and diagnosis.

In adults, MF most commonly manifested as hyperpigmented macules and plaques, erythematous plaques, atrophic lesions, and tumors. In this population, MF remained the most frequently diagnosed PCL subtype, followed by PC-ALCL.

There were notable differences in symptom presentation between age groups and sexes. Adults were more often asymptomatic, and males reported pain more frequently.

When analyzing PCL subtypes in our study, we found that CAEBVI was exclusive to children, specifically males. The updated WHO/EORTC classification contains a new section on EBV-positive LPD in childhood, including hydroa vacciniforme–like LPD and hypersensitivity reactions to mosquito bites.⁴ Both are cutaneous manifestations of CAEBVI with a risk for progression to systemic EBV-positive T-cell or NK-cell lymphoma. These disorders mainly affect children and adolescents from Asia or Indigenous populations from Mexico and Central and South America.^3,4,17 Cases in both female and male patients have been reported, without a clear sex predominance; however, mutations in the Src homology 2 domain containing 1A (SH2D1A) gene recently have been shown to cause X-linked lymphoproliferative disease, which is associated with predilection for EBV infection and subsequent EBV-positive LPD, including CAEBVI.^18,19 Thus, it is possible some of the children with CAEBVI in our study may have an underlying X-linked lymphoproliferative disease, accounting for the male predominance.

Similarly, ENKTCL-NT tended to occur more in children than in adults in our study. Both CAEBVI-LPD and ENKTCL-NT are aggressive lymphomas with a suboptimal prognosis. Although treatment with immunomodulatory agents may lead to temporary remission in most cases, disease progression has been reported in larger cohorts, emphasizing the need for long-term follow-up and more aggressive treatments in severe cases of CAEBVI.^13,17 Treatment options for EBV-positive LPD include mAb such as rituximab, IVIg, HSCT, antiviral agents, interferons α and γ, and corticosteroids.²⁰

Treatment approaches were notably different between children and adults (P<.0001). Monoclonal antibodies, immunomodulatory agents such as thalidomide, IVIg, and HSCT were exclusively used in pediatric patients, reflecting the presence of CAEBVI and ENKTCL-NT (P<.0001). Additionally, edema, blisters, and scars were observed more frequently in children, likely due to the clinical manifestations of these EBV-related disorders.

A recent review of systemic NHL highlighted various age-related differences in clinical presentation, biology, and outcomes.¹³ In general, children tend to present with more aggressive subtypes and achieve better outcomes compared to adults.¹³ These differences may be attributed to variations in tumor biology, immune responses, and/or the benefits of early and intensive interventions in pediatric populations. These findings resonate with our results, as pediatric PCL patients received more aggressive treatments—including mAb, thalidomide, IVIg, and HSCT—likely due to the higher frequency of CAEBVI/ENKTCL-NT; however, we were unable to properly assess treatment outcomes, as many patients, both adults and children, were lost to follow-up.

Overall, our findings and comparisons with existing studies highlight the need for age-specific research and management approaches for PCL. The distinct clinical and biological profiles across age groups highlight opportunities for personalized therapies and further investigation into the molecular drivers of these differences to optimize outcomes for pediatric and adult patients.

When analyzing differences by sex, we found that CAEBVI was diagnosed exclusively in male children, who correspondingly exhibited clinical features such as edema and tumors, with lesions predominantly located on the head and neck. This also influenced treatment approach, as these patients were more likely to receive thalidomide and IVIg. In contrast, PC-ALCL was observed only in female patients, a finding that deviates from previously reported epidemiology.¹⁴ Females with PC-ALCL were more likely to have genital involvement and be asymptomatic, which could suggest a sex-related bias in disease recognition and seeking health care.

Recognizing distinctive clinical manifestations across different diagnoses and age groups can aid health care providers in early identification and accurate diagnosis of PCL. Our findings revealed several notable differences: adults with MF more frequently had scaly lesions, those with PC-ALCL had crusts and ulcers, and those with LyP had erythematous papules. All adults with ENKTCL and primary cutaneous diffuse large B-cell lymphoma, leg-type, presented with tumors. While children with MF had an increased frequency of hypopigmented macules, those with ENKTCL more frequently developed nodules, and children with EBV-MCU often had crusts and ulcers. As has already been mentioned, children with CAEBVI displayed a broad range of lesions, including edema, ulcers, erythematous and hypopigmented plaques, atrophy, blisters, and scars.

Our study was limited by the retrospective design and missing data from one-third of patients, which prevented outcome comparison. We also lacked molecular profiling of patients, which could help refine therapeutic strategies for PCL.¹³ Finally, as both centers included are reference institutions, results may be biased and overestimated and could differ from the rest of the population.

Conclusion

This comparative study of PCL highlighted age-related differences in clinical presentation, diagnostic distribution, and treatment patterns, including a higher prevalence among male children than female children. Adult patients with PCL had a notably longer time to diagnosis than children. The most common type of PCL identified in both age groups and sex categories was MF, but hypopigmented lesions predominated in children with this condition. Epstein-Barr virus–associated PCL occurred almost exclusively in children and manifested with nodules, edema, blisters, and scars. In terms of treatment, children received more aggressive and advanced therapies, including mAb, thalidomide, IVIg, and HSCT. Further prospective research is needed to establish variations in clinical manifestations, diagnoses, treatments, and outcomes.

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of lymphoproliferative malignancies originating from T, B, or natural killer (NK) lymphocytes.¹ Compared to Hodgkin lymphomas, NHLs exhibit a broader clinical spectrum and have a poorer prognosis and frequent extranodal involvement, with the skin being the second most frequent extranodal site.² Primary cutaneous lymphomas (PCLs) are NHLs that are first evident on the skin without evidence of extracutaneous disease at diagnosis. They include a heterogeneous group of cutaneous T-cell lymphomas (CTCLs) and cutaneous B-cell lymphomas. Among CTCLs, mycosis fungoides (MF) is the most prevalent subtype, generally following an indolent course. Cutaneous B-cell lymphomas primarily include follicle center lymphoma and diffuse large B-cell lymphoma.^3,4

The clinical behavior and incidence of PCLs vary dramatically between children and adults, suggesting underlying biologic, immunologic, and genetic differences.^5,6 However, there is a notable lack of comparative studies in the literature addressing these variations, limiting a comprehensive understanding of PCLs and hindering the development of tailored therapeutic strategies. The main objective of this study was to evaluate the different clinical characteristics, subtypes, treatment options, and prognosis in PCLs between pediatric and adult populations.^7,8

Methods

This retrospective observational study included pediatric (aged ≤18 years at diagnosis) and adult (aged >18 years at diagnosis) patients with a clinical and histopathologic diagnosis of PCL who were diagnosed and treated at either of 2 tertiary institutions (Dr. Manuel Gea Gonzalez General Hospital or the National Institute of Pediatrics, both in Mexico City, Mexico) between January 1, 1999, and December 31, 2019. The data analysis included demographic and clinical characteristics, type of PCL (according to World Health Organization [WHO]/European Organisation for Research and Treatment of Cancer [EORTC]) classification,^3,4 treatment administered, and outcome. Disease remission was defined as remittance of clinical PCL manifestations for 3 months or more. Disease control was defined as stable clinical manifestations with no change in PCL stage following treatment initiation. Disease progression was defined as worsening clinical manifestations with an increase in PCL stage and/or development of systemic lymphoma. Beyond similarities and differences across age groups, we also analyzed differences by sex. χ² and Mann-Whitney U tests were used to assess differences between groups. Statistical significance was set at P≤.05. Institutional approval was obtained from both tertiary centers.

Results

Our analysis included a total of 158 patients: 54 (34.2%) were children and 104 (65.8%) were adults. Eighty-eight (55.7%) patients were male (eTable 1). The mean (SD) age at diagnosis was 9.5 (1.9) years in children and 49.7 (18) years in adults. Regarding differences between age groups, adult patients had a similar sex distribution, while in children, the majority of patients were male (37/54 [68.5%]; P=.01).

Overall, the most frequent diagnosis was MF, which occurred in 119 (75.3%) patients, and the most common lesions were erythematous plaques, noted in 95 (60.1%) patients. The lower extremities were the most affected body sites, impacting 127 (80.4%) patients, and the most common treatment was phototherapy, used to treat 110 (69.6%) patients. Reported outcomes included disease control in 45 (28.5%) patients and progression in 36 (22.8%) patients; 50 (31.6%) patients were lost to follow-up. Only 15 (9.5%) patients experienced disease remission, and 12 (7.6%) died.

The mean (SD) time between the onset of symptoms and diagnosis was shorter in children than in adults (18.1 [12.6] months vs 66.2 [34.9] months; P<.001). Regarding involved body sites, the head and neck more frequently affected children than adults (40 [74.1%] vs 33 [31.7%]; P<.001), while the upper extremities were more frequently involved in adults than in children (67 [64.4%] vs 45 [83.3%]; P<.001).

There were significant differences in the morphology of lesions and diagnoses. Children most frequently had hypopigmented plaques (25 [46.3%]) and macules (24 [44.4%])(P<.001) associated with MF, and scars (7 [13.0%]), blisters (6 [11.1%]), and edema (8 [14.8%])(P<.001) associated with positive Epstein-Barr virus (EBV) infection. Adults presented more frequently with hyperpigmented macules (19 [18.3%]) and plaques (37 [35.6%]), erythematous plaques (71 [68.3%]), atrophy (36 [34.6%]), and tumors (32 [30.8%])(P<.001). Adults were more often asymptomatic (86.5% vs 38.8%; P<.001).

Subtypes of PCL differed by age group (eTable 2), with MF being more frequent in adults (87 [83.6%] vs 32 [59.2%]; P<.001), while chronic active positive EBV infection (CAEBVI) manifesting as lymphoproliferative disease (LPD) was exclusive to male children (9 [16.6%])(P<.001). Accordingly, we found variations in systemic treatments used: monoclonal antibodies (mAb), thalidomide, intravenous immunoglobulin (IVIg), and hematopoietic stem cell transplantation (HSCT) were used exclusively for treating children (all P<.001). Outcomes were distributed similarly by age group.

The type of PCL, clinical manifestations, and treatment also varied by sex (eTables 2 and 3). Only males had CAEBVI and presented with edema (8 [9.1%] vs 0%; P<.01). Males also had tumors (23 [26.1%] vs 9 [12.9%]; P=.03) and lesions affecting the head and neck (52 [59.1%] vs 21 [30.0%]; P<.001) more frequently than females. Males were more likely than females to report pain (28 [31.8%] vs 13 [18.6%]; P=.05) and receive systemic treatment with thalidomide (11 [12.5%] vs 1 [1.4%]; P<.001) and IVIg (6 [6.8%] vs 0%; P=.02). Only females were diagnosed with primary cutaneous anaplastic large cell lymphoma (PC-ALCL)(4 [5.7%] vs 0%; P=.03) and had genital involvement (4 [5.7%] vs 0%; P=.03). Females were more likely to be asymptomatic (57 [81.4%] vs 54 [61.4%]; P<.001) or report pruritus (46 [65.7%] vs 44 [50%]; P<.001) and receive local treatment with phototherapy (58 [82.9%] vs 52 [59.1%]; P<.001) compared to males. Although distribution of outcomes was similar by sex, we found males were more frequently lost to follow-up (38 [43.2%] vs 12 [17.1%]; P<.001).

We further searched for differences in clinical manifestations according to the PCL subtype in each age group. The most frequent lesions in 32 children with MF were hypopigmented macules (21 [65.6%]; P<.001)(Figure 1). Three of 5 (60%) children with extranodal NK/T-cell lymphoma, nasal type (ENKTCL), had nodules (P=.002). Of 9 children with CAEBVI, 8 (88.9%) had edema (P<.001), ulcers (P<.001), erythematous plaques (P=.007), and hypopigmented plaques (P=.008); 5 (55.6%) children presented with scars (P<.001) and atrophy (P<.001); and 4 (44.4%) children had blisters (P=.005)(Figure 2). The 2 children with EBV-positive mucocutaneous ulcer (EBV-MCU) had crusts (P=.002) and blisters (P=.01).

Of 87 adults with MF, 54 (62%) had scaly lesions (P=.006)(Figure 3). Of 3 adult patients with PC-ALCL, 2 (66.7%) had crusts (P=.04) and ulcers (P=.05). Two of 3 (66.7%) adults with lymphomatoid papulosis (LyP) had erythematous papules (P<.001). All 4 adult patients with ENKTCL (P=.008) and all 5 patients with primary cutaneous diffuse large B-cell lymphoma, leg-type, had tumors (P<.001).

Finally, we found no differences in outcomes according to types of PCL overall or by age group; however, when categorized by sex, we found males with EBV-MCU more frequently had disease progression than females with EBV-MCU (P=.04).

Comment

Primary cutaneous lymphomas were similarly distributed among males and females (55.6% vs 44.3%, respectively). This slight male predominance was similar to other reports in the literature: one US study reported a male-to-female incidence rate ratio of 1.72, indicating a significantly higher incidence in males (P<.001).⁶ Similar trends have been observed in other geographic regions, with reported male-to-female ratios of 1.56 in Greece and 1.35 in Argentina.^9,10 These findings suggest that PCLs are slightly more prevalent in males across different populations; however, when we stratified by age, pediatric cases of PCL were significantly more frequent in males than in females (68.5% vs. 31.4%; P=.01).

Our analysis revealed that the time to diagnosis was significantly longer in adults than in children (66.2 months vs 18.1 months) for all PCLs (P<.001). The most common type of PCL in both age groups was MF, with a notably higher prevalence in adults than in children (87 [83.7%] vs 32 [59.2%]). The prolonged course of MF in adults, often taking years to progress from early to advanced stages (47.0-52.7 months) may contribute to delayed diagnosis.^8,11,12 Additionally, classic lesions of MF (erythematous scaly plaques) may resemble other common dermatologic conditions, further complicating early recognition and treatment in adults more than in children.^11,12 Conversely, more aggressive and rapidly progressing PCL subtypes, including CAEBVI and ENKTCL-NT, were more frequent in children and would likely be diagnosed more promptly because of the acute onset and fast evolution of signs and symptoms.¹³

Mycosis fungoides is the most common CTCL, followed by CD30+ T-cell disorders such as LyP and PC-ALCL.¹⁴ While MF was the predominant subtype in both age groups, similar to previous reports,^6,7 pediatric patients in our study exhibited distinctive features, such as hypopigmented macules and plaques. Hypopigmented lesions may suggest an underlying immunologic mechanism unique to younger patients, specifically children, in contrast to the hyperpigmented or violaceous lesions predominating in adults.⁷ The hypopigmented variant of MF has been reported to be more prevalent in children, similar to our data, accounting for 54.5% of all pediatric MF cases. These hypopigmented lesions typically manifest at an early stage and follow an indolent course.^15,16 Jung et al⁸ conducted a systematic review of children with MF and reported a mean age at diagnosis of 12.2 years, whereas in our cohort, the mean age was 9.5 years. These findings highlight the different clinical manifestations of MF in children, which may aid in early recognition and diagnosis.

In adults, MF most commonly manifested as hyperpigmented macules and plaques, erythematous plaques, atrophic lesions, and tumors. In this population, MF remained the most frequently diagnosed PCL subtype, followed by PC-ALCL.

There were notable differences in symptom presentation between age groups and sexes. Adults were more often asymptomatic, and males reported pain more frequently.

When analyzing PCL subtypes in our study, we found that CAEBVI was exclusive to children, specifically males. The updated WHO/EORTC classification contains a new section on EBV-positive LPD in childhood, including hydroa vacciniforme–like LPD and hypersensitivity reactions to mosquito bites.⁴ Both are cutaneous manifestations of CAEBVI with a risk for progression to systemic EBV-positive T-cell or NK-cell lymphoma. These disorders mainly affect children and adolescents from Asia or Indigenous populations from Mexico and Central and South America.^3,4,17 Cases in both female and male patients have been reported, without a clear sex predominance; however, mutations in the Src homology 2 domain containing 1A (SH2D1A) gene recently have been shown to cause X-linked lymphoproliferative disease, which is associated with predilection for EBV infection and subsequent EBV-positive LPD, including CAEBVI.^18,19 Thus, it is possible some of the children with CAEBVI in our study may have an underlying X-linked lymphoproliferative disease, accounting for the male predominance.

Similarly, ENKTCL-NT tended to occur more in children than in adults in our study. Both CAEBVI-LPD and ENKTCL-NT are aggressive lymphomas with a suboptimal prognosis. Although treatment with immunomodulatory agents may lead to temporary remission in most cases, disease progression has been reported in larger cohorts, emphasizing the need for long-term follow-up and more aggressive treatments in severe cases of CAEBVI.^13,17 Treatment options for EBV-positive LPD include mAb such as rituximab, IVIg, HSCT, antiviral agents, interferons α and γ, and corticosteroids.²⁰

Treatment approaches were notably different between children and adults (P<.0001). Monoclonal antibodies, immunomodulatory agents such as thalidomide, IVIg, and HSCT were exclusively used in pediatric patients, reflecting the presence of CAEBVI and ENKTCL-NT (P<.0001). Additionally, edema, blisters, and scars were observed more frequently in children, likely due to the clinical manifestations of these EBV-related disorders.

A recent review of systemic NHL highlighted various age-related differences in clinical presentation, biology, and outcomes.¹³ In general, children tend to present with more aggressive subtypes and achieve better outcomes compared to adults.¹³ These differences may be attributed to variations in tumor biology, immune responses, and/or the benefits of early and intensive interventions in pediatric populations. These findings resonate with our results, as pediatric PCL patients received more aggressive treatments—including mAb, thalidomide, IVIg, and HSCT—likely due to the higher frequency of CAEBVI/ENKTCL-NT; however, we were unable to properly assess treatment outcomes, as many patients, both adults and children, were lost to follow-up.

Overall, our findings and comparisons with existing studies highlight the need for age-specific research and management approaches for PCL. The distinct clinical and biological profiles across age groups highlight opportunities for personalized therapies and further investigation into the molecular drivers of these differences to optimize outcomes for pediatric and adult patients.

When analyzing differences by sex, we found that CAEBVI was diagnosed exclusively in male children, who correspondingly exhibited clinical features such as edema and tumors, with lesions predominantly located on the head and neck. This also influenced treatment approach, as these patients were more likely to receive thalidomide and IVIg. In contrast, PC-ALCL was observed only in female patients, a finding that deviates from previously reported epidemiology.¹⁴ Females with PC-ALCL were more likely to have genital involvement and be asymptomatic, which could suggest a sex-related bias in disease recognition and seeking health care.

Recognizing distinctive clinical manifestations across different diagnoses and age groups can aid health care providers in early identification and accurate diagnosis of PCL. Our findings revealed several notable differences: adults with MF more frequently had scaly lesions, those with PC-ALCL had crusts and ulcers, and those with LyP had erythematous papules. All adults with ENKTCL and primary cutaneous diffuse large B-cell lymphoma, leg-type, presented with tumors. While children with MF had an increased frequency of hypopigmented macules, those with ENKTCL more frequently developed nodules, and children with EBV-MCU often had crusts and ulcers. As has already been mentioned, children with CAEBVI displayed a broad range of lesions, including edema, ulcers, erythematous and hypopigmented plaques, atrophy, blisters, and scars.

Our study was limited by the retrospective design and missing data from one-third of patients, which prevented outcome comparison. We also lacked molecular profiling of patients, which could help refine therapeutic strategies for PCL.¹³ Finally, as both centers included are reference institutions, results may be biased and overestimated and could differ from the rest of the population.

Conclusion

This comparative study of PCL highlighted age-related differences in clinical presentation, diagnostic distribution, and treatment patterns, including a higher prevalence among male children than female children. Adult patients with PCL had a notably longer time to diagnosis than children. The most common type of PCL identified in both age groups and sex categories was MF, but hypopigmented lesions predominated in children with this condition. Epstein-Barr virus–associated PCL occurred almost exclusively in children and manifested with nodules, edema, blisters, and scars. In terms of treatment, children received more aggressive and advanced therapies, including mAb, thalidomide, IVIg, and HSCT. Further prospective research is needed to establish variations in clinical manifestations, diagnoses, treatments, and outcomes.

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of lymphoproliferative malignancies originating from T, B, or natural killer (NK) lymphocytes.¹ Compared to Hodgkin lymphomas, NHLs exhibit a broader clinical spectrum and have a poorer prognosis and frequent extranodal involvement, with the skin being the second most frequent extranodal site.² Primary cutaneous lymphomas (PCLs) are NHLs that are first evident on the skin without evidence of extracutaneous disease at diagnosis. They include a heterogeneous group of cutaneous T-cell lymphomas (CTCLs) and cutaneous B-cell lymphomas. Among CTCLs, mycosis fungoides (MF) is the most prevalent subtype, generally following an indolent course. Cutaneous B-cell lymphomas primarily include follicle center lymphoma and diffuse large B-cell lymphoma.^3,4

The clinical behavior and incidence of PCLs vary dramatically between children and adults, suggesting underlying biologic, immunologic, and genetic differences.^5,6 However, there is a notable lack of comparative studies in the literature addressing these variations, limiting a comprehensive understanding of PCLs and hindering the development of tailored therapeutic strategies. The main objective of this study was to evaluate the different clinical characteristics, subtypes, treatment options, and prognosis in PCLs between pediatric and adult populations.^7,8

Methods

This retrospective observational study included pediatric (aged ≤18 years at diagnosis) and adult (aged >18 years at diagnosis) patients with a clinical and histopathologic diagnosis of PCL who were diagnosed and treated at either of 2 tertiary institutions (Dr. Manuel Gea Gonzalez General Hospital or the National Institute of Pediatrics, both in Mexico City, Mexico) between January 1, 1999, and December 31, 2019. The data analysis included demographic and clinical characteristics, type of PCL (according to World Health Organization [WHO]/European Organisation for Research and Treatment of Cancer [EORTC]) classification,^3,4 treatment administered, and outcome. Disease remission was defined as remittance of clinical PCL manifestations for 3 months or more. Disease control was defined as stable clinical manifestations with no change in PCL stage following treatment initiation. Disease progression was defined as worsening clinical manifestations with an increase in PCL stage and/or development of systemic lymphoma. Beyond similarities and differences across age groups, we also analyzed differences by sex. χ² and Mann-Whitney U tests were used to assess differences between groups. Statistical significance was set at P≤.05. Institutional approval was obtained from both tertiary centers.

Results

Our analysis included a total of 158 patients: 54 (34.2%) were children and 104 (65.8%) were adults. Eighty-eight (55.7%) patients were male (eTable 1). The mean (SD) age at diagnosis was 9.5 (1.9) years in children and 49.7 (18) years in adults. Regarding differences between age groups, adult patients had a similar sex distribution, while in children, the majority of patients were male (37/54 [68.5%]; P=.01).

Overall, the most frequent diagnosis was MF, which occurred in 119 (75.3%) patients, and the most common lesions were erythematous plaques, noted in 95 (60.1%) patients. The lower extremities were the most affected body sites, impacting 127 (80.4%) patients, and the most common treatment was phototherapy, used to treat 110 (69.6%) patients. Reported outcomes included disease control in 45 (28.5%) patients and progression in 36 (22.8%) patients; 50 (31.6%) patients were lost to follow-up. Only 15 (9.5%) patients experienced disease remission, and 12 (7.6%) died.

The mean (SD) time between the onset of symptoms and diagnosis was shorter in children than in adults (18.1 [12.6] months vs 66.2 [34.9] months; P<.001). Regarding involved body sites, the head and neck more frequently affected children than adults (40 [74.1%] vs 33 [31.7%]; P<.001), while the upper extremities were more frequently involved in adults than in children (67 [64.4%] vs 45 [83.3%]; P<.001).

There were significant differences in the morphology of lesions and diagnoses. Children most frequently had hypopigmented plaques (25 [46.3%]) and macules (24 [44.4%])(P<.001) associated with MF, and scars (7 [13.0%]), blisters (6 [11.1%]), and edema (8 [14.8%])(P<.001) associated with positive Epstein-Barr virus (EBV) infection. Adults presented more frequently with hyperpigmented macules (19 [18.3%]) and plaques (37 [35.6%]), erythematous plaques (71 [68.3%]), atrophy (36 [34.6%]), and tumors (32 [30.8%])(P<.001). Adults were more often asymptomatic (86.5% vs 38.8%; P<.001).

Subtypes of PCL differed by age group (eTable 2), with MF being more frequent in adults (87 [83.6%] vs 32 [59.2%]; P<.001), while chronic active positive EBV infection (CAEBVI) manifesting as lymphoproliferative disease (LPD) was exclusive to male children (9 [16.6%])(P<.001). Accordingly, we found variations in systemic treatments used: monoclonal antibodies (mAb), thalidomide, intravenous immunoglobulin (IVIg), and hematopoietic stem cell transplantation (HSCT) were used exclusively for treating children (all P<.001). Outcomes were distributed similarly by age group.

The type of PCL, clinical manifestations, and treatment also varied by sex (eTables 2 and 3). Only males had CAEBVI and presented with edema (8 [9.1%] vs 0%; P<.01). Males also had tumors (23 [26.1%] vs 9 [12.9%]; P=.03) and lesions affecting the head and neck (52 [59.1%] vs 21 [30.0%]; P<.001) more frequently than females. Males were more likely than females to report pain (28 [31.8%] vs 13 [18.6%]; P=.05) and receive systemic treatment with thalidomide (11 [12.5%] vs 1 [1.4%]; P<.001) and IVIg (6 [6.8%] vs 0%; P=.02). Only females were diagnosed with primary cutaneous anaplastic large cell lymphoma (PC-ALCL)(4 [5.7%] vs 0%; P=.03) and had genital involvement (4 [5.7%] vs 0%; P=.03). Females were more likely to be asymptomatic (57 [81.4%] vs 54 [61.4%]; P<.001) or report pruritus (46 [65.7%] vs 44 [50%]; P<.001) and receive local treatment with phototherapy (58 [82.9%] vs 52 [59.1%]; P<.001) compared to males. Although distribution of outcomes was similar by sex, we found males were more frequently lost to follow-up (38 [43.2%] vs 12 [17.1%]; P<.001).

We further searched for differences in clinical manifestations according to the PCL subtype in each age group. The most frequent lesions in 32 children with MF were hypopigmented macules (21 [65.6%]; P<.001)(Figure 1). Three of 5 (60%) children with extranodal NK/T-cell lymphoma, nasal type (ENKTCL), had nodules (P=.002). Of 9 children with CAEBVI, 8 (88.9%) had edema (P<.001), ulcers (P<.001), erythematous plaques (P=.007), and hypopigmented plaques (P=.008); 5 (55.6%) children presented with scars (P<.001) and atrophy (P<.001); and 4 (44.4%) children had blisters (P=.005)(Figure 2). The 2 children with EBV-positive mucocutaneous ulcer (EBV-MCU) had crusts (P=.002) and blisters (P=.01).

Of 87 adults with MF, 54 (62%) had scaly lesions (P=.006)(Figure 3). Of 3 adult patients with PC-ALCL, 2 (66.7%) had crusts (P=.04) and ulcers (P=.05). Two of 3 (66.7%) adults with lymphomatoid papulosis (LyP) had erythematous papules (P<.001). All 4 adult patients with ENKTCL (P=.008) and all 5 patients with primary cutaneous diffuse large B-cell lymphoma, leg-type, had tumors (P<.001).

Finally, we found no differences in outcomes according to types of PCL overall or by age group; however, when categorized by sex, we found males with EBV-MCU more frequently had disease progression than females with EBV-MCU (P=.04).

Comment

Primary cutaneous lymphomas were similarly distributed among males and females (55.6% vs 44.3%, respectively). This slight male predominance was similar to other reports in the literature: one US study reported a male-to-female incidence rate ratio of 1.72, indicating a significantly higher incidence in males (P<.001).⁶ Similar trends have been observed in other geographic regions, with reported male-to-female ratios of 1.56 in Greece and 1.35 in Argentina.^9,10 These findings suggest that PCLs are slightly more prevalent in males across different populations; however, when we stratified by age, pediatric cases of PCL were significantly more frequent in males than in females (68.5% vs. 31.4%; P=.01).

Our analysis revealed that the time to diagnosis was significantly longer in adults than in children (66.2 months vs 18.1 months) for all PCLs (P<.001). The most common type of PCL in both age groups was MF, with a notably higher prevalence in adults than in children (87 [83.7%] vs 32 [59.2%]). The prolonged course of MF in adults, often taking years to progress from early to advanced stages (47.0-52.7 months) may contribute to delayed diagnosis.^8,11,12 Additionally, classic lesions of MF (erythematous scaly plaques) may resemble other common dermatologic conditions, further complicating early recognition and treatment in adults more than in children.^11,12 Conversely, more aggressive and rapidly progressing PCL subtypes, including CAEBVI and ENKTCL-NT, were more frequent in children and would likely be diagnosed more promptly because of the acute onset and fast evolution of signs and symptoms.¹³

Mycosis fungoides is the most common CTCL, followed by CD30+ T-cell disorders such as LyP and PC-ALCL.¹⁴ While MF was the predominant subtype in both age groups, similar to previous reports,^6,7 pediatric patients in our study exhibited distinctive features, such as hypopigmented macules and plaques. Hypopigmented lesions may suggest an underlying immunologic mechanism unique to younger patients, specifically children, in contrast to the hyperpigmented or violaceous lesions predominating in adults.⁷ The hypopigmented variant of MF has been reported to be more prevalent in children, similar to our data, accounting for 54.5% of all pediatric MF cases. These hypopigmented lesions typically manifest at an early stage and follow an indolent course.^15,16 Jung et al⁸ conducted a systematic review of children with MF and reported a mean age at diagnosis of 12.2 years, whereas in our cohort, the mean age was 9.5 years. These findings highlight the different clinical manifestations of MF in children, which may aid in early recognition and diagnosis.

In adults, MF most commonly manifested as hyperpigmented macules and plaques, erythematous plaques, atrophic lesions, and tumors. In this population, MF remained the most frequently diagnosed PCL subtype, followed by PC-ALCL.

There were notable differences in symptom presentation between age groups and sexes. Adults were more often asymptomatic, and males reported pain more frequently.

When analyzing PCL subtypes in our study, we found that CAEBVI was exclusive to children, specifically males. The updated WHO/EORTC classification contains a new section on EBV-positive LPD in childhood, including hydroa vacciniforme–like LPD and hypersensitivity reactions to mosquito bites.⁴ Both are cutaneous manifestations of CAEBVI with a risk for progression to systemic EBV-positive T-cell or NK-cell lymphoma. These disorders mainly affect children and adolescents from Asia or Indigenous populations from Mexico and Central and South America.^3,4,17 Cases in both female and male patients have been reported, without a clear sex predominance; however, mutations in the Src homology 2 domain containing 1A (SH2D1A) gene recently have been shown to cause X-linked lymphoproliferative disease, which is associated with predilection for EBV infection and subsequent EBV-positive LPD, including CAEBVI.^18,19 Thus, it is possible some of the children with CAEBVI in our study may have an underlying X-linked lymphoproliferative disease, accounting for the male predominance.

Similarly, ENKTCL-NT tended to occur more in children than in adults in our study. Both CAEBVI-LPD and ENKTCL-NT are aggressive lymphomas with a suboptimal prognosis. Although treatment with immunomodulatory agents may lead to temporary remission in most cases, disease progression has been reported in larger cohorts, emphasizing the need for long-term follow-up and more aggressive treatments in severe cases of CAEBVI.^13,17 Treatment options for EBV-positive LPD include mAb such as rituximab, IVIg, HSCT, antiviral agents, interferons α and γ, and corticosteroids.²⁰

Treatment approaches were notably different between children and adults (P<.0001). Monoclonal antibodies, immunomodulatory agents such as thalidomide, IVIg, and HSCT were exclusively used in pediatric patients, reflecting the presence of CAEBVI and ENKTCL-NT (P<.0001). Additionally, edema, blisters, and scars were observed more frequently in children, likely due to the clinical manifestations of these EBV-related disorders.

A recent review of systemic NHL highlighted various age-related differences in clinical presentation, biology, and outcomes.¹³ In general, children tend to present with more aggressive subtypes and achieve better outcomes compared to adults.¹³ These differences may be attributed to variations in tumor biology, immune responses, and/or the benefits of early and intensive interventions in pediatric populations. These findings resonate with our results, as pediatric PCL patients received more aggressive treatments—including mAb, thalidomide, IVIg, and HSCT—likely due to the higher frequency of CAEBVI/ENKTCL-NT; however, we were unable to properly assess treatment outcomes, as many patients, both adults and children, were lost to follow-up.

Overall, our findings and comparisons with existing studies highlight the need for age-specific research and management approaches for PCL. The distinct clinical and biological profiles across age groups highlight opportunities for personalized therapies and further investigation into the molecular drivers of these differences to optimize outcomes for pediatric and adult patients.

When analyzing differences by sex, we found that CAEBVI was diagnosed exclusively in male children, who correspondingly exhibited clinical features such as edema and tumors, with lesions predominantly located on the head and neck. This also influenced treatment approach, as these patients were more likely to receive thalidomide and IVIg. In contrast, PC-ALCL was observed only in female patients, a finding that deviates from previously reported epidemiology.¹⁴ Females with PC-ALCL were more likely to have genital involvement and be asymptomatic, which could suggest a sex-related bias in disease recognition and seeking health care.

Recognizing distinctive clinical manifestations across different diagnoses and age groups can aid health care providers in early identification and accurate diagnosis of PCL. Our findings revealed several notable differences: adults with MF more frequently had scaly lesions, those with PC-ALCL had crusts and ulcers, and those with LyP had erythematous papules. All adults with ENKTCL and primary cutaneous diffuse large B-cell lymphoma, leg-type, presented with tumors. While children with MF had an increased frequency of hypopigmented macules, those with ENKTCL more frequently developed nodules, and children with EBV-MCU often had crusts and ulcers. As has already been mentioned, children with CAEBVI displayed a broad range of lesions, including edema, ulcers, erythematous and hypopigmented plaques, atrophy, blisters, and scars.

Our study was limited by the retrospective design and missing data from one-third of patients, which prevented outcome comparison. We also lacked molecular profiling of patients, which could help refine therapeutic strategies for PCL.¹³ Finally, as both centers included are reference institutions, results may be biased and overestimated and could differ from the rest of the population.

Conclusion

This comparative study of PCL highlighted age-related differences in clinical presentation, diagnostic distribution, and treatment patterns, including a higher prevalence among male children than female children. Adult patients with PCL had a notably longer time to diagnosis than children. The most common type of PCL identified in both age groups and sex categories was MF, but hypopigmented lesions predominated in children with this condition. Epstein-Barr virus–associated PCL occurred almost exclusively in children and manifested with nodules, edema, blisters, and scars. In terms of treatment, children received more aggressive and advanced therapies, including mAb, thalidomide, IVIg, and HSCT. Further prospective research is needed to establish variations in clinical manifestations, diagnoses, treatments, and outcomes.

Practice Gap

Accurate biopsy site identification prior to Mohs micrographic surgery (MMS) can be challenging, particularly on the scalp, where excellent healing, field cancerization, prior procedures, large surface area, and hair density may complicate localization. Accurate site identification is further hindered when patients are unable to recall the biopsy location, when the biopsy and MMS are performed by different clinicians, or when photographic documentation is absent. Scalp lesions pose an additional challenge because even high-quality photographs may fail to capture subtle landmarks that are obscured by hair.

Wrong-site surgery was the most common serious error reported in a survey of 150 dermatologists, accounting for 19.0% of these errors.¹ Research has shown that dermatologists may misidentify biopsy sites in up to 17.6% of cases, and patients (eg, if a patient goes to a dermatologic surgeon and is asked to identify the biopsy site for the surgeon) in up to 25.5% (N=278).² Additionally, a survey of Mohs surgeons revealed that 14.0% of 42 malpractice cases were due to wrong-site surgery.³ A Delphi consensus study assessing possible preventive interventions found that the best way to document the site is with a photograph in association with landmarks and diagrams.⁴

The Technique

The hair-cut sign is a simple and effective technique for identifying biopsy sites on the scalp. Hair at the biopsy site typically is cut during biopsy; as the surrounding hair grows, the resulting short tuft serves as an anatomic marker that can persist for weeks to months to facilitate accurate site localization by the Mohs surgeon (Figure). This noninvasive, equipment-free method may be particularly useful when documentation or photography is limited. To maximize its effectiveness, clinical staff should avoid trimming the area before physician verification of the site. The technique is most effective in patients with longer hair and when the interval between biopsy and surgery is less than 3 months, as hair regrowth may reduce contrast with the surrounding scalp.

Practice Implications

Accurate biopsy site identification is a critical component of patient safety in dermatologic surgery, particularly on the scalp, where traditional localization strategies may be unreliable. The hair-cut sign is a simple, reliable, no-cost, and reproducible adjunct to photography, anatomic documentation, and patient verification that may improve site localization and help reduce the risk for wrong-site surgery in select patients to complement standard practices. Incorporating the hair-cut sign into routine scalp surgery workflow represents a low-burden intervention that may improve accuracy when other documentation is limited.

Practice Gap

Accurate biopsy site identification prior to Mohs micrographic surgery (MMS) can be challenging, particularly on the scalp, where excellent healing, field cancerization, prior procedures, large surface area, and hair density may complicate localization. Accurate site identification is further hindered when patients are unable to recall the biopsy location, when the biopsy and MMS are performed by different clinicians, or when photographic documentation is absent. Scalp lesions pose an additional challenge because even high-quality photographs may fail to capture subtle landmarks that are obscured by hair.

Wrong-site surgery was the most common serious error reported in a survey of 150 dermatologists, accounting for 19.0% of these errors.¹ Research has shown that dermatologists may misidentify biopsy sites in up to 17.6% of cases, and patients (eg, if a patient goes to a dermatologic surgeon and is asked to identify the biopsy site for the surgeon) in up to 25.5% (N=278).² Additionally, a survey of Mohs surgeons revealed that 14.0% of 42 malpractice cases were due to wrong-site surgery.³ A Delphi consensus study assessing possible preventive interventions found that the best way to document the site is with a photograph in association with landmarks and diagrams.⁴

The Technique

The hair-cut sign is a simple and effective technique for identifying biopsy sites on the scalp. Hair at the biopsy site typically is cut during biopsy; as the surrounding hair grows, the resulting short tuft serves as an anatomic marker that can persist for weeks to months to facilitate accurate site localization by the Mohs surgeon (Figure). This noninvasive, equipment-free method may be particularly useful when documentation or photography is limited. To maximize its effectiveness, clinical staff should avoid trimming the area before physician verification of the site. The technique is most effective in patients with longer hair and when the interval between biopsy and surgery is less than 3 months, as hair regrowth may reduce contrast with the surrounding scalp.

Practice Implications

Accurate biopsy site identification is a critical component of patient safety in dermatologic surgery, particularly on the scalp, where traditional localization strategies may be unreliable. The hair-cut sign is a simple, reliable, no-cost, and reproducible adjunct to photography, anatomic documentation, and patient verification that may improve site localization and help reduce the risk for wrong-site surgery in select patients to complement standard practices. Incorporating the hair-cut sign into routine scalp surgery workflow represents a low-burden intervention that may improve accuracy when other documentation is limited.

Practice Gap

Accurate biopsy site identification prior to Mohs micrographic surgery (MMS) can be challenging, particularly on the scalp, where excellent healing, field cancerization, prior procedures, large surface area, and hair density may complicate localization. Accurate site identification is further hindered when patients are unable to recall the biopsy location, when the biopsy and MMS are performed by different clinicians, or when photographic documentation is absent. Scalp lesions pose an additional challenge because even high-quality photographs may fail to capture subtle landmarks that are obscured by hair.

Wrong-site surgery was the most common serious error reported in a survey of 150 dermatologists, accounting for 19.0% of these errors.¹ Research has shown that dermatologists may misidentify biopsy sites in up to 17.6% of cases, and patients (eg, if a patient goes to a dermatologic surgeon and is asked to identify the biopsy site for the surgeon) in up to 25.5% (N=278).² Additionally, a survey of Mohs surgeons revealed that 14.0% of 42 malpractice cases were due to wrong-site surgery.³ A Delphi consensus study assessing possible preventive interventions found that the best way to document the site is with a photograph in association with landmarks and diagrams.⁴

The Technique

The hair-cut sign is a simple and effective technique for identifying biopsy sites on the scalp. Hair at the biopsy site typically is cut during biopsy; as the surrounding hair grows, the resulting short tuft serves as an anatomic marker that can persist for weeks to months to facilitate accurate site localization by the Mohs surgeon (Figure). This noninvasive, equipment-free method may be particularly useful when documentation or photography is limited. To maximize its effectiveness, clinical staff should avoid trimming the area before physician verification of the site. The technique is most effective in patients with longer hair and when the interval between biopsy and surgery is less than 3 months, as hair regrowth may reduce contrast with the surrounding scalp.

Practice Implications

Accurate biopsy site identification is a critical component of patient safety in dermatologic surgery, particularly on the scalp, where traditional localization strategies may be unreliable. The hair-cut sign is a simple, reliable, no-cost, and reproducible adjunct to photography, anatomic documentation, and patient verification that may improve site localization and help reduce the risk for wrong-site surgery in select patients to complement standard practices. Incorporating the hair-cut sign into routine scalp surgery workflow represents a low-burden intervention that may improve accuracy when other documentation is limited.

Dermatophyte infections, commonly referred to as tinea, involve the superficial epidermis and are caused by fungi belonging primarily to the genera Trichophyton, Epidermophyton, and Microsporum.¹ Malassezia are lipophilic yeasts found in the normal skin flora that can overgrow within hair follicles and trigger an inflammatory response. While both fungal infections are associated with several classic clinical features, they can demonstrate variable clinical morphology, especially when modified by previous topical treatments. In such cases, fungal infections may mimic other forms of inflammatory dermatitis and can be misdiagnosed.

Acne vulgaris is one of the most prevalent dermatologic conditions and typically is diagnosed clinically based on characteristic morphology and distribution. Despite their distinct etiologies, dermatophyte infections and acne vulgaris may manifest with overlapping features, particularly in acne-prone regions such as the face, chest, and back, which may result in diagnostic errors and inappropriate management. This review highlights dermatophyte infections as an underrecognized mimic of acne vulgaris, emphasizing key clinical distinguishing features, common diagnostic pitfalls, and a practical approach to evaluation.

Clinical Overlap of Dermatophyte Infections and Acne

Despite their fundamentally different etiologies, dermatophyte infections and acne may demonstrate overlapping clinical morphology and anatomic distribution, creating diagnostic challenges and increasing misdiagnosis risk. Clinically, acne is characterized by the presence of open and closed comedones as well as inflammatory papules, pustules, nodules, and occasionally cysts.² In contrast, dermatophyte infections classically manifest as annular erythematous plaques with peripheral scale and central clearing, primarily due to their superficial confinement to the stratum corneum; however, in certain cases the dermatophyte invades the hair follicle, which can lead to the formation of folliculocentric pustules.¹ This is known as dermatophyte folliculitis and may closely resemble the pustules observed in acne.

Follicular invasion by dermatophytes is more likely in cases in which infection has been misdiagnosed as a noninfectious inflammatory dermatosis, (eg, atopic dermatitis) and treated with topical corticosteroids. Corticosteroid-induced local immunosuppression facilitates deeper and more extensive proliferation of the invading fungus, including into the hair follicle. Topical corticosteroid use may further obscure the diagnosis of a dermatophyte infection by masking its hallmark features such as scale and annularity.³ This steroid-altered dermatophyte infection is referred to as tinea incognita and may be misdiagnosed as acne or another inflammatory dermatosis. When dermatophytes extend from the stratum corneum into the dermis due to local immunosuppression (eg, corticosteroid use), trauma, shaving, or occlusion, the resulting deep follicular infection is known as Majocchi granuloma.

Further complicating the diagnostic picture is the substantial anatomic and epidemiologic overlap between dermatophyte infections and acne vulgaris. Acne preferentially affects sebum-rich areas, including the face, chest, and back.² Dermatophytes, by contrast, thrive in keratinized tissue.¹ Because areas with a higher density of hair follicles contain abundant keratin, dermatophyte infections often involve the same sebum-rich regions affected by acne. Both acne and tinea are observed frequently in adolescents, possibly due to hormonal changes that increase sebum production and create an environment conducive to fungal growth.⁴

Pityrosporum Folliculitis Manifesting as Acne Vulgaris

Although it has been widely popularized in lay and social media, the term fungal acne is a misnomer; this entity more accurately represents a fungal folliculitis manifesting as an acneform eruption. In most cases, fungal acne refers to Malassezia folliculitis, also called pityrosporum folliculitis, which is caused by Malassezia species. Malassezia are not dermatophytes but rather lipophilic yeasts found in the normal skin flora. Whereas dermatophytes are drawn to highly keratinized tissue, Malassezia are drawn to lipid-rich environments of the skin. In these conditions, including sweating and hot or humid environments, Malassezia may proliferate to pathogenic levels within the hair follicle.⁵

Clinically, Malassezia folliculitis manifests as monomorphic, folliculocentric, dome-shaped papules and pustules with occasional progression to nodules or cysts in more severe cases.⁵ Lesions typically are intensely pruritic, a distinguishing feature that helps differentiate them from acne vulgaris.⁶ The eruption predominantly involves sebum-rich areas, including the face, hairline, chest, and upper back (Figure 1).⁵ Overall, the clinical presentation often more closely resembles steroid-induced acne than classic acne vulgaris. Antibiotic exposure is an important risk factor, potentially due to disruption of the normal skin microbiome and subsequent yeast overgrowth; for example, in a retrospective review of 110 patients (age range, 0-21 years) with Malassezia folliculitis, more than 75% had recently received antibiotics for treatment of acne.⁶ Additional predisposing factors include corticosteroid use and immunosuppression.⁵

Importantly, Malassezia folliculitis and acne vulgaris may coexist, further complicating diagnosis. In a study of 217 patients with acne vulgaris, cytologic evaluation demonstrated Malassezia overgrowth (defined as >6 spores per high-power field) in approximately 25% of patients, of whom 70% responded to antifungal therapy.⁷ Similarly, a study of 300 patients with newly diagnosed acne found a prevalence of Malassezia folliculitis of almost 30%. Patients with concurrent Malassezia folliculitis and acne were more likely to report pruritus and have involvement of the scalp, hairline, and upper back compared to those with acne alone.⁸

Tinea Faciei and Tinea Barbae Manifesting as Facial Acne

Tinea faciei describes a dermatophyte infection of the nonbearded area of the face, whereas infection of the beard-bearing region is known as tinea barbae. In North America, Trichophyton species are the leading cause of tinea faciei.¹ Clinically, tinea faciei manifests as one or more erythematous scaly plaques on the face, often associated with pruritus. Lesions often assume an annular shape with an advancing border along which pustules, vesicles, or crusting can be observed. In cases of inappropriate treatment with topical corticosteroids, lesions may lose their characteristic scale and annularity and instead become papular, mimicking the acneform eruptions of facial acne vulgaris (Figure 2).

Like tinea faciei, tinea barbae most commonly develops from infection with Trichophyton species but differs in its clinical presentation. While superficial scaly variants exist, tinea barbae more frequently manifests as a deep, papular, inflammatory folliculitis. This deeper form typically is caused by follicular infiltration by zoophilic dermatophytes such as Trichophyton verrucosum and Microsporum canis. Not surprisingly, infection by these zoophilic dermatophytes is associated with exposure to animals such as cattle, horses, dogs, and cats, and a history of agricultural work may offer a helpful clue to diagnosis.⁹ The tender, nodular, or nodulocystic lesions of severe tinea barbae infections may closely resemble nodulocystic acne.

Misdiagnosis, inappropriate treatment, and diagnostic delays are common in patients with tinea faciei and tinea barbae. In a retrospective study of 818 cases of tinea faciei, approximately 30% of patients had received prior corticosteroid treatment at the time of diagnosis.¹⁰ Similarly, a cross-sectional study of 7 adult patients with tinea barbae in a Portuguese hospital found that 3 cases initially were misdiagnosed and that in 2 cases potent topical steroids were previously applied.¹¹ Finally, in a retrospective review of 38 patients with mycologically confirmed tinea faciei, the mean duration from symptom onset to diagnosis was 3.4 months.¹⁰ Notably, nearly 60% of patients had concomitant dermatophyte infections at other body sites, most commonly involving the feet and toes, highlighting that recognition of dermatophyte infections elsewhere on physical examination may provide an important diagnostic clue.¹²

Tinea Corporis Manifesting as Truncal Acne

Tinea corporis refers to a dermatophyte infection involving the glabrous, or hairless, skin of the trunk and extremities. Trichophyton rubrum accounts for 80% to 90% of the pathogenic strains that cause tinea corporis.¹ As with other variants of superficial dermatophyte infections, tinea corporis classically manifests as annular erythematous plaques with peripheral scale and central clearing, distinguished by its involvement of the trunk. Pruritus of lesions is variable.¹

Inappropriate treatment of tinea corporis with topical corticosteroids may induce a morphologic change in the infection so that it resembles the lesions of truncal acne, which characteristically involves the chest, upper back, and shoulders, and less frequently the lower back and abdomen.² As in other forms of acne vulgaris, the lesions are characterized by a mixture of inflammatory papules, pustules, and comedones. When differentiating tinea corporis and truncal acne, consider the distribution and symmetry of the lesions. Dermatophyte infections often are localized to one area of the trunk and are asymmetric. In contrast, acne typically is generalized and manifests more symmetrically.

Additional clinical clues may aid in differentiation. An acneform eruption involving other seborrheic areas of the body (eg, the face) supports a diagnosis of truncal acne. Conversely, the presence of tinea elsewhere, particularly on the hands or feet, may suggest tinea corporis. Finally, although pustules can be seen with tinea corporis, the presence of true comedones is a key distinguishing factor favoring acne vulgaris.

Importantly, resistant dermatophyte infections have emerged as a growing concern among public health experts over the past decade. A recently described species, Trichophyton indotineae, has played a substantial role in driving these cases.¹³ While early US cases largely were limited to patients who had travelled to Bangladesh, infections now are increasingly reported in individuals without travel history.¹³ Trichophyton indotineae most commonly involves the trunk, extremities, and groin, which mirrors the distribution of truncal acne. Further complicating the clinical picture is the lack of response to standard antifungal therapies such as oral terbinafine in these patients.¹³ Failure to consider this diagnosis, particularly given its recent recognition, may lead physicians to empirically switch treatment to topical or systemic corticosteroids. This can further alter lesion morphology and increase the likelihood of misdiagnosis.

Helpful Bedside Diagnostic Tools

When clinical findings are equivocal, bedside diagnostic tools, including dermoscopy, a Wood lamp, potassium hydroxide (KOH) preparation, and histopathology, may be helpful in differentiating cutaneous fungal infections from acne.

Dermoscopy—In an observational study of 81 patients with fungal folliculitis, dermoscopy demonstrated a diagnostic accuracy of 76.5%.¹⁴ Dermoscopic findings in a cohort of 45 patients with KOH-confirmed Malassezia folliculitis included folliculocentric lesions and background erythema (100%); dotted, linear, or tortuous vessels (89%); fine white scale (78%); perifollicular hypopigmentation (64%); coiled or looped hairs (58%); and broken hairs (13%).¹⁵ Moreover, in a study comparing 36 microscopically confirmed tinea cases with 40 negative cases, peripheral scales (odds ratio [OR], 5.2; 95% CI, 2.0-13.5), moth-eaten scales (OR, 3.9; 95% CI, 1.9-8.1), broken hairs (OR, 5.8; 95% CI, 2.0-16.6), and outward-peeling scales (OR, 14.3; 95% CI, 1.3-155.2) were predictive of tinea.¹⁶ Dermoscopic findings in a cross-sectional study of 100 clinically diagnosed tinea cases included diffuse erythema with whitish scars (100.0%), follicular micropustules (36.7%), brown spots with a white-yellow halo (20.0%), wavy or broken hairs (13.0%), and Morse code– like vellus hairs (3.0%).¹⁷ In tinea incognito, features such as Morse code–like hairs, deformable translucent hairs, comma and corkscrew hairs, and perifollicular scaling may persist despite corticosteroid use.^18,19

Wood Lamp Examination—Wood lamp examination may be a helpful adjunctive tool for diagnosis of Malassezia folliculitis. In a study of 264 patients with folliculitis (49 of whom were diagnosed with Malassezia folliculitis), Wood lamp examination demonstrated yellow-green fluorescence in 66.7% of cases.²⁰ In contrast, this method has limited utility in diagnosing common dermatophyte infections, as only Microsporum and a small subset of Trichophyton species fluoresce.²¹ In a study of 50 pediatric patients with tinea capitis, Microsporum cases were identified via Wood lamp examination by bright green fluorescence. Wood lamp examination demonstrated 73% sensitivity and 100% specificity for Microsporum canis, confirmed by microscopy and culture, indicating that positive results are highly reliable for this genus, though false negatives may occur.²²

Some dermatoscopes incorporate a Wood lamp, enabling UV-induced fluorescence dermoscopy (UVFD). In a study of 208 patients with nonneoplastic dermatoses, UVFD of tinea showed light green hair shaft concretions in 27% (4/15) of patients and no fluorescence in 73% (11/15), whereas Malassezia folliculitis demonstrated blue follicular concretions in 85% (11/13) and acne showed disruption of uniform follicular red fluorescence in 81% (13/16).23 However, these dermatoscopes are not widely available.

KOH Preparation—While the aforementioned tests are useful and require minimal effort, the diagnostic test of choice for cutaneous fungal infections remains the KOH preparation, which is fast and inexpensive and offers immediate results, often while the patient is still in the office. The test should be performed by obtaining scale, ideally from an active lesion border, by gently scraping the stratum corneum, often with a #15 blade. For sampling of pustules or when there is concern for Malassezia folliculitis, optimal technique involves unroofing a pustule and transferring its contents onto a slide for KOH preparation. The specimen then is treated with KOH, a keratolytic agent that dissolves keratinocytes and facilitates visualization of fungal elements under light microscopy. Reported sensitivity and specificity of KOH preparation are approximately 73% and 78%, respectively.²⁴ Notably, sensitivity and specificity of KOH is highly dependent on expertise. A fungal culture also can be collected and sent for microbiologic analysis, although results often are delayed. In one pooled analysis of tinea pedis using clinical assessment as the reference standard, fungal culture demonstrated a sensitivity of 42% and specificity of 78%, though these estimates are highly dependent on study design and sampling technique.²⁴

Histopathology—Finally, histopathologic evaluation may be considered in diagnostically challenging cases. Histology of Malassezia folliculitis demonstrates fungal spores within the follicular lumen, while histology of acne shows irregular keratin plugging, nuclear debris within the follicular lumen, and intrafollicular inflammation. Notably, perifollicular inflammatory infiltrates are histologically similar in acne and Malassezia folliculitis.²⁵

Practical Diagnostic Approach to Differentiating Dermatophyte Infections from Acne

For physicians encountering papulopustular eruptions in acne-prone regions, distinguishing acne vulgaris from dermatophyte infection can be challenging. A stepwise approach incorporating history, morphology, and distribution can improve diagnostic accuracy and guide appropriate management.

First, obtain a thorough treatment history. Presumed acne that has failed to respond to appropriate acne therapies should prompt reconsideration of the diagnosis. Prior treatment with topical corticosteroids should be specifically assessed. Patients may not volunteer this history unless directly asked. Corticosteroid use can alter the clinical appearance of dermatophyte infections, leading to diagnostic confusion.

Second, use morphologic features and lesion distribution as diagnostic clues. The presence of comedones favors acne vulgaris, whereas their absence should raise suspicion for tinea. It is important to note, however, that certain dermatophyte infections may manifest with folliculocentric pustules, which can mimic closed comedones or inflammatory lesions seen in acne. Acne vulgaris also typically demonstrates a bilateral and relatively symmetric distribution, particularly on the face, chest, and upper back. In contrast, dermatophyte infections are more often asymmetric or localized, especially in early stages.

Patient-reported symptoms and a complete skin examination can further aid in differentiation. While acne may occasionally be pruritic, pain or tenderness is more commonly reported. In contrast, dermatophyte infections often will have prominent pruritus, which frequently is the patient’s primary complaint. The presence of tinea on the hands or feet supports a diagnosis of dermatophyte infection, whereas concurrent acneform lesions in classic seborrheic regions favor acne vulgaris. The Table outlines key clinical features that help distinguish dermatophyte infections from acne vulgaris.

When the diagnosis remains unclear after clinical assessment, physicians may utilize both bedside and laboratory tests, including dermoscopy, Wood lamp examination, in-office KOH preparation, and/or fungal culture, as discussed previously. In cases of diagnostic uncertainty, empiric antifungal therapy is preferred over topical corticosteroid therapy, as corticosteroids may exacerbate an underlying dermatophyte infection. In refractory or diagnostically challenging cases, skin biopsy with periodic acid–Schiff staining may be considered to confirm the presence of fungal organisms. Biopsy generally is reserved for cases that fail to respond to empiric therapy or when diagnostic confirmation is strongly desired. Figure 3 provides an algorithmic approach to distinguishing acne vulgaris from dermatophyte infection.

Final Thoughts

Dermatophyte infections are a common but often overlooked mimic of acne vulgaris. Clinically, acne is characterized by comedones, whereas dermatophyte infections typically demonstrate scale, though these features can be less apparent in modified presentations. In cases of diagnostic uncertainty, physicians should keep dermatophyte infections in mind and be comfortable performing bedside KOH preparations to support timely diagnosis. Early recognition is important to reduce morbidity and avoid inappropriate treatments, particularly corticosteroids, which can worsen the infection and delay improvement.

Dermatophyte infections, commonly referred to as tinea, involve the superficial epidermis and are caused by fungi belonging primarily to the genera Trichophyton, Epidermophyton, and Microsporum.¹ Malassezia are lipophilic yeasts found in the normal skin flora that can overgrow within hair follicles and trigger an inflammatory response. While both fungal infections are associated with several classic clinical features, they can demonstrate variable clinical morphology, especially when modified by previous topical treatments. In such cases, fungal infections may mimic other forms of inflammatory dermatitis and can be misdiagnosed.

Acne vulgaris is one of the most prevalent dermatologic conditions and typically is diagnosed clinically based on characteristic morphology and distribution. Despite their distinct etiologies, dermatophyte infections and acne vulgaris may manifest with overlapping features, particularly in acne-prone regions such as the face, chest, and back, which may result in diagnostic errors and inappropriate management. This review highlights dermatophyte infections as an underrecognized mimic of acne vulgaris, emphasizing key clinical distinguishing features, common diagnostic pitfalls, and a practical approach to evaluation.

Clinical Overlap of Dermatophyte Infections and Acne

Despite their fundamentally different etiologies, dermatophyte infections and acne may demonstrate overlapping clinical morphology and anatomic distribution, creating diagnostic challenges and increasing misdiagnosis risk. Clinically, acne is characterized by the presence of open and closed comedones as well as inflammatory papules, pustules, nodules, and occasionally cysts.² In contrast, dermatophyte infections classically manifest as annular erythematous plaques with peripheral scale and central clearing, primarily due to their superficial confinement to the stratum corneum; however, in certain cases the dermatophyte invades the hair follicle, which can lead to the formation of folliculocentric pustules.¹ This is known as dermatophyte folliculitis and may closely resemble the pustules observed in acne.

Follicular invasion by dermatophytes is more likely in cases in which infection has been misdiagnosed as a noninfectious inflammatory dermatosis, (eg, atopic dermatitis) and treated with topical corticosteroids. Corticosteroid-induced local immunosuppression facilitates deeper and more extensive proliferation of the invading fungus, including into the hair follicle. Topical corticosteroid use may further obscure the diagnosis of a dermatophyte infection by masking its hallmark features such as scale and annularity.³ This steroid-altered dermatophyte infection is referred to as tinea incognita and may be misdiagnosed as acne or another inflammatory dermatosis. When dermatophytes extend from the stratum corneum into the dermis due to local immunosuppression (eg, corticosteroid use), trauma, shaving, or occlusion, the resulting deep follicular infection is known as Majocchi granuloma.

Further complicating the diagnostic picture is the substantial anatomic and epidemiologic overlap between dermatophyte infections and acne vulgaris. Acne preferentially affects sebum-rich areas, including the face, chest, and back.² Dermatophytes, by contrast, thrive in keratinized tissue.¹ Because areas with a higher density of hair follicles contain abundant keratin, dermatophyte infections often involve the same sebum-rich regions affected by acne. Both acne and tinea are observed frequently in adolescents, possibly due to hormonal changes that increase sebum production and create an environment conducive to fungal growth.⁴

Pityrosporum Folliculitis Manifesting as Acne Vulgaris

Although it has been widely popularized in lay and social media, the term fungal acne is a misnomer; this entity more accurately represents a fungal folliculitis manifesting as an acneform eruption. In most cases, fungal acne refers to Malassezia folliculitis, also called pityrosporum folliculitis, which is caused by Malassezia species. Malassezia are not dermatophytes but rather lipophilic yeasts found in the normal skin flora. Whereas dermatophytes are drawn to highly keratinized tissue, Malassezia are drawn to lipid-rich environments of the skin. In these conditions, including sweating and hot or humid environments, Malassezia may proliferate to pathogenic levels within the hair follicle.⁵

Clinically, Malassezia folliculitis manifests as monomorphic, folliculocentric, dome-shaped papules and pustules with occasional progression to nodules or cysts in more severe cases.⁵ Lesions typically are intensely pruritic, a distinguishing feature that helps differentiate them from acne vulgaris.⁶ The eruption predominantly involves sebum-rich areas, including the face, hairline, chest, and upper back (Figure 1).⁵ Overall, the clinical presentation often more closely resembles steroid-induced acne than classic acne vulgaris. Antibiotic exposure is an important risk factor, potentially due to disruption of the normal skin microbiome and subsequent yeast overgrowth; for example, in a retrospective review of 110 patients (age range, 0-21 years) with Malassezia folliculitis, more than 75% had recently received antibiotics for treatment of acne.⁶ Additional predisposing factors include corticosteroid use and immunosuppression.⁵

Importantly, Malassezia folliculitis and acne vulgaris may coexist, further complicating diagnosis. In a study of 217 patients with acne vulgaris, cytologic evaluation demonstrated Malassezia overgrowth (defined as >6 spores per high-power field) in approximately 25% of patients, of whom 70% responded to antifungal therapy.⁷ Similarly, a study of 300 patients with newly diagnosed acne found a prevalence of Malassezia folliculitis of almost 30%. Patients with concurrent Malassezia folliculitis and acne were more likely to report pruritus and have involvement of the scalp, hairline, and upper back compared to those with acne alone.⁸

Tinea Faciei and Tinea Barbae Manifesting as Facial Acne

Tinea faciei describes a dermatophyte infection of the nonbearded area of the face, whereas infection of the beard-bearing region is known as tinea barbae. In North America, Trichophyton species are the leading cause of tinea faciei.¹ Clinically, tinea faciei manifests as one or more erythematous scaly plaques on the face, often associated with pruritus. Lesions often assume an annular shape with an advancing border along which pustules, vesicles, or crusting can be observed. In cases of inappropriate treatment with topical corticosteroids, lesions may lose their characteristic scale and annularity and instead become papular, mimicking the acneform eruptions of facial acne vulgaris (Figure 2).

Like tinea faciei, tinea barbae most commonly develops from infection with Trichophyton species but differs in its clinical presentation. While superficial scaly variants exist, tinea barbae more frequently manifests as a deep, papular, inflammatory folliculitis. This deeper form typically is caused by follicular infiltration by zoophilic dermatophytes such as Trichophyton verrucosum and Microsporum canis. Not surprisingly, infection by these zoophilic dermatophytes is associated with exposure to animals such as cattle, horses, dogs, and cats, and a history of agricultural work may offer a helpful clue to diagnosis.⁹ The tender, nodular, or nodulocystic lesions of severe tinea barbae infections may closely resemble nodulocystic acne.

Misdiagnosis, inappropriate treatment, and diagnostic delays are common in patients with tinea faciei and tinea barbae. In a retrospective study of 818 cases of tinea faciei, approximately 30% of patients had received prior corticosteroid treatment at the time of diagnosis.¹⁰ Similarly, a cross-sectional study of 7 adult patients with tinea barbae in a Portuguese hospital found that 3 cases initially were misdiagnosed and that in 2 cases potent topical steroids were previously applied.¹¹ Finally, in a retrospective review of 38 patients with mycologically confirmed tinea faciei, the mean duration from symptom onset to diagnosis was 3.4 months.¹⁰ Notably, nearly 60% of patients had concomitant dermatophyte infections at other body sites, most commonly involving the feet and toes, highlighting that recognition of dermatophyte infections elsewhere on physical examination may provide an important diagnostic clue.¹²

Tinea Corporis Manifesting as Truncal Acne

Tinea corporis refers to a dermatophyte infection involving the glabrous, or hairless, skin of the trunk and extremities. Trichophyton rubrum accounts for 80% to 90% of the pathogenic strains that cause tinea corporis.¹ As with other variants of superficial dermatophyte infections, tinea corporis classically manifests as annular erythematous plaques with peripheral scale and central clearing, distinguished by its involvement of the trunk. Pruritus of lesions is variable.¹

Inappropriate treatment of tinea corporis with topical corticosteroids may induce a morphologic change in the infection so that it resembles the lesions of truncal acne, which characteristically involves the chest, upper back, and shoulders, and less frequently the lower back and abdomen.² As in other forms of acne vulgaris, the lesions are characterized by a mixture of inflammatory papules, pustules, and comedones. When differentiating tinea corporis and truncal acne, consider the distribution and symmetry of the lesions. Dermatophyte infections often are localized to one area of the trunk and are asymmetric. In contrast, acne typically is generalized and manifests more symmetrically.

Additional clinical clues may aid in differentiation. An acneform eruption involving other seborrheic areas of the body (eg, the face) supports a diagnosis of truncal acne. Conversely, the presence of tinea elsewhere, particularly on the hands or feet, may suggest tinea corporis. Finally, although pustules can be seen with tinea corporis, the presence of true comedones is a key distinguishing factor favoring acne vulgaris.

Importantly, resistant dermatophyte infections have emerged as a growing concern among public health experts over the past decade. A recently described species, Trichophyton indotineae, has played a substantial role in driving these cases.¹³ While early US cases largely were limited to patients who had travelled to Bangladesh, infections now are increasingly reported in individuals without travel history.¹³ Trichophyton indotineae most commonly involves the trunk, extremities, and groin, which mirrors the distribution of truncal acne. Further complicating the clinical picture is the lack of response to standard antifungal therapies such as oral terbinafine in these patients.¹³ Failure to consider this diagnosis, particularly given its recent recognition, may lead physicians to empirically switch treatment to topical or systemic corticosteroids. This can further alter lesion morphology and increase the likelihood of misdiagnosis.

Helpful Bedside Diagnostic Tools

When clinical findings are equivocal, bedside diagnostic tools, including dermoscopy, a Wood lamp, potassium hydroxide (KOH) preparation, and histopathology, may be helpful in differentiating cutaneous fungal infections from acne.

Dermoscopy—In an observational study of 81 patients with fungal folliculitis, dermoscopy demonstrated a diagnostic accuracy of 76.5%.¹⁴ Dermoscopic findings in a cohort of 45 patients with KOH-confirmed Malassezia folliculitis included folliculocentric lesions and background erythema (100%); dotted, linear, or tortuous vessels (89%); fine white scale (78%); perifollicular hypopigmentation (64%); coiled or looped hairs (58%); and broken hairs (13%).¹⁵ Moreover, in a study comparing 36 microscopically confirmed tinea cases with 40 negative cases, peripheral scales (odds ratio [OR], 5.2; 95% CI, 2.0-13.5), moth-eaten scales (OR, 3.9; 95% CI, 1.9-8.1), broken hairs (OR, 5.8; 95% CI, 2.0-16.6), and outward-peeling scales (OR, 14.3; 95% CI, 1.3-155.2) were predictive of tinea.¹⁶ Dermoscopic findings in a cross-sectional study of 100 clinically diagnosed tinea cases included diffuse erythema with whitish scars (100.0%), follicular micropustules (36.7%), brown spots with a white-yellow halo (20.0%), wavy or broken hairs (13.0%), and Morse code– like vellus hairs (3.0%).¹⁷ In tinea incognito, features such as Morse code–like hairs, deformable translucent hairs, comma and corkscrew hairs, and perifollicular scaling may persist despite corticosteroid use.^18,19

Wood Lamp Examination—Wood lamp examination may be a helpful adjunctive tool for diagnosis of Malassezia folliculitis. In a study of 264 patients with folliculitis (49 of whom were diagnosed with Malassezia folliculitis), Wood lamp examination demonstrated yellow-green fluorescence in 66.7% of cases.²⁰ In contrast, this method has limited utility in diagnosing common dermatophyte infections, as only Microsporum and a small subset of Trichophyton species fluoresce.²¹ In a study of 50 pediatric patients with tinea capitis, Microsporum cases were identified via Wood lamp examination by bright green fluorescence. Wood lamp examination demonstrated 73% sensitivity and 100% specificity for Microsporum canis, confirmed by microscopy and culture, indicating that positive results are highly reliable for this genus, though false negatives may occur.²²

Some dermatoscopes incorporate a Wood lamp, enabling UV-induced fluorescence dermoscopy (UVFD). In a study of 208 patients with nonneoplastic dermatoses, UVFD of tinea showed light green hair shaft concretions in 27% (4/15) of patients and no fluorescence in 73% (11/15), whereas Malassezia folliculitis demonstrated blue follicular concretions in 85% (11/13) and acne showed disruption of uniform follicular red fluorescence in 81% (13/16).23 However, these dermatoscopes are not widely available.

KOH Preparation—While the aforementioned tests are useful and require minimal effort, the diagnostic test of choice for cutaneous fungal infections remains the KOH preparation, which is fast and inexpensive and offers immediate results, often while the patient is still in the office. The test should be performed by obtaining scale, ideally from an active lesion border, by gently scraping the stratum corneum, often with a #15 blade. For sampling of pustules or when there is concern for Malassezia folliculitis, optimal technique involves unroofing a pustule and transferring its contents onto a slide for KOH preparation. The specimen then is treated with KOH, a keratolytic agent that dissolves keratinocytes and facilitates visualization of fungal elements under light microscopy. Reported sensitivity and specificity of KOH preparation are approximately 73% and 78%, respectively.²⁴ Notably, sensitivity and specificity of KOH is highly dependent on expertise. A fungal culture also can be collected and sent for microbiologic analysis, although results often are delayed. In one pooled analysis of tinea pedis using clinical assessment as the reference standard, fungal culture demonstrated a sensitivity of 42% and specificity of 78%, though these estimates are highly dependent on study design and sampling technique.²⁴

Histopathology—Finally, histopathologic evaluation may be considered in diagnostically challenging cases. Histology of Malassezia folliculitis demonstrates fungal spores within the follicular lumen, while histology of acne shows irregular keratin plugging, nuclear debris within the follicular lumen, and intrafollicular inflammation. Notably, perifollicular inflammatory infiltrates are histologically similar in acne and Malassezia folliculitis.²⁵

Practical Diagnostic Approach to Differentiating Dermatophyte Infections from Acne

For physicians encountering papulopustular eruptions in acne-prone regions, distinguishing acne vulgaris from dermatophyte infection can be challenging. A stepwise approach incorporating history, morphology, and distribution can improve diagnostic accuracy and guide appropriate management.

First, obtain a thorough treatment history. Presumed acne that has failed to respond to appropriate acne therapies should prompt reconsideration of the diagnosis. Prior treatment with topical corticosteroids should be specifically assessed. Patients may not volunteer this history unless directly asked. Corticosteroid use can alter the clinical appearance of dermatophyte infections, leading to diagnostic confusion.

Second, use morphologic features and lesion distribution as diagnostic clues. The presence of comedones favors acne vulgaris, whereas their absence should raise suspicion for tinea. It is important to note, however, that certain dermatophyte infections may manifest with folliculocentric pustules, which can mimic closed comedones or inflammatory lesions seen in acne. Acne vulgaris also typically demonstrates a bilateral and relatively symmetric distribution, particularly on the face, chest, and upper back. In contrast, dermatophyte infections are more often asymmetric or localized, especially in early stages.

Patient-reported symptoms and a complete skin examination can further aid in differentiation. While acne may occasionally be pruritic, pain or tenderness is more commonly reported. In contrast, dermatophyte infections often will have prominent pruritus, which frequently is the patient’s primary complaint. The presence of tinea on the hands or feet supports a diagnosis of dermatophyte infection, whereas concurrent acneform lesions in classic seborrheic regions favor acne vulgaris. The Table outlines key clinical features that help distinguish dermatophyte infections from acne vulgaris.

When the diagnosis remains unclear after clinical assessment, physicians may utilize both bedside and laboratory tests, including dermoscopy, Wood lamp examination, in-office KOH preparation, and/or fungal culture, as discussed previously. In cases of diagnostic uncertainty, empiric antifungal therapy is preferred over topical corticosteroid therapy, as corticosteroids may exacerbate an underlying dermatophyte infection. In refractory or diagnostically challenging cases, skin biopsy with periodic acid–Schiff staining may be considered to confirm the presence of fungal organisms. Biopsy generally is reserved for cases that fail to respond to empiric therapy or when diagnostic confirmation is strongly desired. Figure 3 provides an algorithmic approach to distinguishing acne vulgaris from dermatophyte infection.

Final Thoughts

Dermatophyte infections are a common but often overlooked mimic of acne vulgaris. Clinically, acne is characterized by comedones, whereas dermatophyte infections typically demonstrate scale, though these features can be less apparent in modified presentations. In cases of diagnostic uncertainty, physicians should keep dermatophyte infections in mind and be comfortable performing bedside KOH preparations to support timely diagnosis. Early recognition is important to reduce morbidity and avoid inappropriate treatments, particularly corticosteroids, which can worsen the infection and delay improvement.

Dermatophyte infections, commonly referred to as tinea, involve the superficial epidermis and are caused by fungi belonging primarily to the genera Trichophyton, Epidermophyton, and Microsporum.¹ Malassezia are lipophilic yeasts found in the normal skin flora that can overgrow within hair follicles and trigger an inflammatory response. While both fungal infections are associated with several classic clinical features, they can demonstrate variable clinical morphology, especially when modified by previous topical treatments. In such cases, fungal infections may mimic other forms of inflammatory dermatitis and can be misdiagnosed.

Acne vulgaris is one of the most prevalent dermatologic conditions and typically is diagnosed clinically based on characteristic morphology and distribution. Despite their distinct etiologies, dermatophyte infections and acne vulgaris may manifest with overlapping features, particularly in acne-prone regions such as the face, chest, and back, which may result in diagnostic errors and inappropriate management. This review highlights dermatophyte infections as an underrecognized mimic of acne vulgaris, emphasizing key clinical distinguishing features, common diagnostic pitfalls, and a practical approach to evaluation.

Clinical Overlap of Dermatophyte Infections and Acne

Despite their fundamentally different etiologies, dermatophyte infections and acne may demonstrate overlapping clinical morphology and anatomic distribution, creating diagnostic challenges and increasing misdiagnosis risk. Clinically, acne is characterized by the presence of open and closed comedones as well as inflammatory papules, pustules, nodules, and occasionally cysts.² In contrast, dermatophyte infections classically manifest as annular erythematous plaques with peripheral scale and central clearing, primarily due to their superficial confinement to the stratum corneum; however, in certain cases the dermatophyte invades the hair follicle, which can lead to the formation of folliculocentric pustules.¹ This is known as dermatophyte folliculitis and may closely resemble the pustules observed in acne.

Follicular invasion by dermatophytes is more likely in cases in which infection has been misdiagnosed as a noninfectious inflammatory dermatosis, (eg, atopic dermatitis) and treated with topical corticosteroids. Corticosteroid-induced local immunosuppression facilitates deeper and more extensive proliferation of the invading fungus, including into the hair follicle. Topical corticosteroid use may further obscure the diagnosis of a dermatophyte infection by masking its hallmark features such as scale and annularity.³ This steroid-altered dermatophyte infection is referred to as tinea incognita and may be misdiagnosed as acne or another inflammatory dermatosis. When dermatophytes extend from the stratum corneum into the dermis due to local immunosuppression (eg, corticosteroid use), trauma, shaving, or occlusion, the resulting deep follicular infection is known as Majocchi granuloma.

Further complicating the diagnostic picture is the substantial anatomic and epidemiologic overlap between dermatophyte infections and acne vulgaris. Acne preferentially affects sebum-rich areas, including the face, chest, and back.² Dermatophytes, by contrast, thrive in keratinized tissue.¹ Because areas with a higher density of hair follicles contain abundant keratin, dermatophyte infections often involve the same sebum-rich regions affected by acne. Both acne and tinea are observed frequently in adolescents, possibly due to hormonal changes that increase sebum production and create an environment conducive to fungal growth.⁴

Pityrosporum Folliculitis Manifesting as Acne Vulgaris

Although it has been widely popularized in lay and social media, the term fungal acne is a misnomer; this entity more accurately represents a fungal folliculitis manifesting as an acneform eruption. In most cases, fungal acne refers to Malassezia folliculitis, also called pityrosporum folliculitis, which is caused by Malassezia species. Malassezia are not dermatophytes but rather lipophilic yeasts found in the normal skin flora. Whereas dermatophytes are drawn to highly keratinized tissue, Malassezia are drawn to lipid-rich environments of the skin. In these conditions, including sweating and hot or humid environments, Malassezia may proliferate to pathogenic levels within the hair follicle.⁵

Clinically, Malassezia folliculitis manifests as monomorphic, folliculocentric, dome-shaped papules and pustules with occasional progression to nodules or cysts in more severe cases.⁵ Lesions typically are intensely pruritic, a distinguishing feature that helps differentiate them from acne vulgaris.⁶ The eruption predominantly involves sebum-rich areas, including the face, hairline, chest, and upper back (Figure 1).⁵ Overall, the clinical presentation often more closely resembles steroid-induced acne than classic acne vulgaris. Antibiotic exposure is an important risk factor, potentially due to disruption of the normal skin microbiome and subsequent yeast overgrowth; for example, in a retrospective review of 110 patients (age range, 0-21 years) with Malassezia folliculitis, more than 75% had recently received antibiotics for treatment of acne.⁶ Additional predisposing factors include corticosteroid use and immunosuppression.⁵

Importantly, Malassezia folliculitis and acne vulgaris may coexist, further complicating diagnosis. In a study of 217 patients with acne vulgaris, cytologic evaluation demonstrated Malassezia overgrowth (defined as >6 spores per high-power field) in approximately 25% of patients, of whom 70% responded to antifungal therapy.⁷ Similarly, a study of 300 patients with newly diagnosed acne found a prevalence of Malassezia folliculitis of almost 30%. Patients with concurrent Malassezia folliculitis and acne were more likely to report pruritus and have involvement of the scalp, hairline, and upper back compared to those with acne alone.⁸

Tinea Faciei and Tinea Barbae Manifesting as Facial Acne

Tinea faciei describes a dermatophyte infection of the nonbearded area of the face, whereas infection of the beard-bearing region is known as tinea barbae. In North America, Trichophyton species are the leading cause of tinea faciei.¹ Clinically, tinea faciei manifests as one or more erythematous scaly plaques on the face, often associated with pruritus. Lesions often assume an annular shape with an advancing border along which pustules, vesicles, or crusting can be observed. In cases of inappropriate treatment with topical corticosteroids, lesions may lose their characteristic scale and annularity and instead become papular, mimicking the acneform eruptions of facial acne vulgaris (Figure 2).

Like tinea faciei, tinea barbae most commonly develops from infection with Trichophyton species but differs in its clinical presentation. While superficial scaly variants exist, tinea barbae more frequently manifests as a deep, papular, inflammatory folliculitis. This deeper form typically is caused by follicular infiltration by zoophilic dermatophytes such as Trichophyton verrucosum and Microsporum canis. Not surprisingly, infection by these zoophilic dermatophytes is associated with exposure to animals such as cattle, horses, dogs, and cats, and a history of agricultural work may offer a helpful clue to diagnosis.⁹ The tender, nodular, or nodulocystic lesions of severe tinea barbae infections may closely resemble nodulocystic acne.

Misdiagnosis, inappropriate treatment, and diagnostic delays are common in patients with tinea faciei and tinea barbae. In a retrospective study of 818 cases of tinea faciei, approximately 30% of patients had received prior corticosteroid treatment at the time of diagnosis.¹⁰ Similarly, a cross-sectional study of 7 adult patients with tinea barbae in a Portuguese hospital found that 3 cases initially were misdiagnosed and that in 2 cases potent topical steroids were previously applied.¹¹ Finally, in a retrospective review of 38 patients with mycologically confirmed tinea faciei, the mean duration from symptom onset to diagnosis was 3.4 months.¹⁰ Notably, nearly 60% of patients had concomitant dermatophyte infections at other body sites, most commonly involving the feet and toes, highlighting that recognition of dermatophyte infections elsewhere on physical examination may provide an important diagnostic clue.¹²

Tinea Corporis Manifesting as Truncal Acne

Tinea corporis refers to a dermatophyte infection involving the glabrous, or hairless, skin of the trunk and extremities. Trichophyton rubrum accounts for 80% to 90% of the pathogenic strains that cause tinea corporis.¹ As with other variants of superficial dermatophyte infections, tinea corporis classically manifests as annular erythematous plaques with peripheral scale and central clearing, distinguished by its involvement of the trunk. Pruritus of lesions is variable.¹

Inappropriate treatment of tinea corporis with topical corticosteroids may induce a morphologic change in the infection so that it resembles the lesions of truncal acne, which characteristically involves the chest, upper back, and shoulders, and less frequently the lower back and abdomen.² As in other forms of acne vulgaris, the lesions are characterized by a mixture of inflammatory papules, pustules, and comedones. When differentiating tinea corporis and truncal acne, consider the distribution and symmetry of the lesions. Dermatophyte infections often are localized to one area of the trunk and are asymmetric. In contrast, acne typically is generalized and manifests more symmetrically.

Additional clinical clues may aid in differentiation. An acneform eruption involving other seborrheic areas of the body (eg, the face) supports a diagnosis of truncal acne. Conversely, the presence of tinea elsewhere, particularly on the hands or feet, may suggest tinea corporis. Finally, although pustules can be seen with tinea corporis, the presence of true comedones is a key distinguishing factor favoring acne vulgaris.

Importantly, resistant dermatophyte infections have emerged as a growing concern among public health experts over the past decade. A recently described species, Trichophyton indotineae, has played a substantial role in driving these cases.¹³ While early US cases largely were limited to patients who had travelled to Bangladesh, infections now are increasingly reported in individuals without travel history.¹³ Trichophyton indotineae most commonly involves the trunk, extremities, and groin, which mirrors the distribution of truncal acne. Further complicating the clinical picture is the lack of response to standard antifungal therapies such as oral terbinafine in these patients.¹³ Failure to consider this diagnosis, particularly given its recent recognition, may lead physicians to empirically switch treatment to topical or systemic corticosteroids. This can further alter lesion morphology and increase the likelihood of misdiagnosis.

Helpful Bedside Diagnostic Tools

When clinical findings are equivocal, bedside diagnostic tools, including dermoscopy, a Wood lamp, potassium hydroxide (KOH) preparation, and histopathology, may be helpful in differentiating cutaneous fungal infections from acne.

Dermoscopy—In an observational study of 81 patients with fungal folliculitis, dermoscopy demonstrated a diagnostic accuracy of 76.5%.¹⁴ Dermoscopic findings in a cohort of 45 patients with KOH-confirmed Malassezia folliculitis included folliculocentric lesions and background erythema (100%); dotted, linear, or tortuous vessels (89%); fine white scale (78%); perifollicular hypopigmentation (64%); coiled or looped hairs (58%); and broken hairs (13%).¹⁵ Moreover, in a study comparing 36 microscopically confirmed tinea cases with 40 negative cases, peripheral scales (odds ratio [OR], 5.2; 95% CI, 2.0-13.5), moth-eaten scales (OR, 3.9; 95% CI, 1.9-8.1), broken hairs (OR, 5.8; 95% CI, 2.0-16.6), and outward-peeling scales (OR, 14.3; 95% CI, 1.3-155.2) were predictive of tinea.¹⁶ Dermoscopic findings in a cross-sectional study of 100 clinically diagnosed tinea cases included diffuse erythema with whitish scars (100.0%), follicular micropustules (36.7%), brown spots with a white-yellow halo (20.0%), wavy or broken hairs (13.0%), and Morse code– like vellus hairs (3.0%).¹⁷ In tinea incognito, features such as Morse code–like hairs, deformable translucent hairs, comma and corkscrew hairs, and perifollicular scaling may persist despite corticosteroid use.^18,19

Wood Lamp Examination—Wood lamp examination may be a helpful adjunctive tool for diagnosis of Malassezia folliculitis. In a study of 264 patients with folliculitis (49 of whom were diagnosed with Malassezia folliculitis), Wood lamp examination demonstrated yellow-green fluorescence in 66.7% of cases.²⁰ In contrast, this method has limited utility in diagnosing common dermatophyte infections, as only Microsporum and a small subset of Trichophyton species fluoresce.²¹ In a study of 50 pediatric patients with tinea capitis, Microsporum cases were identified via Wood lamp examination by bright green fluorescence. Wood lamp examination demonstrated 73% sensitivity and 100% specificity for Microsporum canis, confirmed by microscopy and culture, indicating that positive results are highly reliable for this genus, though false negatives may occur.²²

Some dermatoscopes incorporate a Wood lamp, enabling UV-induced fluorescence dermoscopy (UVFD). In a study of 208 patients with nonneoplastic dermatoses, UVFD of tinea showed light green hair shaft concretions in 27% (4/15) of patients and no fluorescence in 73% (11/15), whereas Malassezia folliculitis demonstrated blue follicular concretions in 85% (11/13) and acne showed disruption of uniform follicular red fluorescence in 81% (13/16).23 However, these dermatoscopes are not widely available.

KOH Preparation—While the aforementioned tests are useful and require minimal effort, the diagnostic test of choice for cutaneous fungal infections remains the KOH preparation, which is fast and inexpensive and offers immediate results, often while the patient is still in the office. The test should be performed by obtaining scale, ideally from an active lesion border, by gently scraping the stratum corneum, often with a #15 blade. For sampling of pustules or when there is concern for Malassezia folliculitis, optimal technique involves unroofing a pustule and transferring its contents onto a slide for KOH preparation. The specimen then is treated with KOH, a keratolytic agent that dissolves keratinocytes and facilitates visualization of fungal elements under light microscopy. Reported sensitivity and specificity of KOH preparation are approximately 73% and 78%, respectively.²⁴ Notably, sensitivity and specificity of KOH is highly dependent on expertise. A fungal culture also can be collected and sent for microbiologic analysis, although results often are delayed. In one pooled analysis of tinea pedis using clinical assessment as the reference standard, fungal culture demonstrated a sensitivity of 42% and specificity of 78%, though these estimates are highly dependent on study design and sampling technique.²⁴

Histopathology—Finally, histopathologic evaluation may be considered in diagnostically challenging cases. Histology of Malassezia folliculitis demonstrates fungal spores within the follicular lumen, while histology of acne shows irregular keratin plugging, nuclear debris within the follicular lumen, and intrafollicular inflammation. Notably, perifollicular inflammatory infiltrates are histologically similar in acne and Malassezia folliculitis.²⁵

Practical Diagnostic Approach to Differentiating Dermatophyte Infections from Acne

For physicians encountering papulopustular eruptions in acne-prone regions, distinguishing acne vulgaris from dermatophyte infection can be challenging. A stepwise approach incorporating history, morphology, and distribution can improve diagnostic accuracy and guide appropriate management.

First, obtain a thorough treatment history. Presumed acne that has failed to respond to appropriate acne therapies should prompt reconsideration of the diagnosis. Prior treatment with topical corticosteroids should be specifically assessed. Patients may not volunteer this history unless directly asked. Corticosteroid use can alter the clinical appearance of dermatophyte infections, leading to diagnostic confusion.

Second, use morphologic features and lesion distribution as diagnostic clues. The presence of comedones favors acne vulgaris, whereas their absence should raise suspicion for tinea. It is important to note, however, that certain dermatophyte infections may manifest with folliculocentric pustules, which can mimic closed comedones or inflammatory lesions seen in acne. Acne vulgaris also typically demonstrates a bilateral and relatively symmetric distribution, particularly on the face, chest, and upper back. In contrast, dermatophyte infections are more often asymmetric or localized, especially in early stages.

Patient-reported symptoms and a complete skin examination can further aid in differentiation. While acne may occasionally be pruritic, pain or tenderness is more commonly reported. In contrast, dermatophyte infections often will have prominent pruritus, which frequently is the patient’s primary complaint. The presence of tinea on the hands or feet supports a diagnosis of dermatophyte infection, whereas concurrent acneform lesions in classic seborrheic regions favor acne vulgaris. The Table outlines key clinical features that help distinguish dermatophyte infections from acne vulgaris.

When the diagnosis remains unclear after clinical assessment, physicians may utilize both bedside and laboratory tests, including dermoscopy, Wood lamp examination, in-office KOH preparation, and/or fungal culture, as discussed previously. In cases of diagnostic uncertainty, empiric antifungal therapy is preferred over topical corticosteroid therapy, as corticosteroids may exacerbate an underlying dermatophyte infection. In refractory or diagnostically challenging cases, skin biopsy with periodic acid–Schiff staining may be considered to confirm the presence of fungal organisms. Biopsy generally is reserved for cases that fail to respond to empiric therapy or when diagnostic confirmation is strongly desired. Figure 3 provides an algorithmic approach to distinguishing acne vulgaris from dermatophyte infection.

Final Thoughts

Dermatophyte infections are a common but often overlooked mimic of acne vulgaris. Clinically, acne is characterized by comedones, whereas dermatophyte infections typically demonstrate scale, though these features can be less apparent in modified presentations. In cases of diagnostic uncertainty, physicians should keep dermatophyte infections in mind and be comfortable performing bedside KOH preparations to support timely diagnosis. Early recognition is important to reduce morbidity and avoid inappropriate treatments, particularly corticosteroids, which can worsen the infection and delay improvement.