Article

THE DIAGNOSIS: Lepromatous Leprosy

Histopathology showed collections of epithelioid to sarcoidal granulomas throughout the dermis and clustered around nerve bundles with a grenz zone at the dermoepidermal junction. Fite stain was positive for acid-fast bacteria, which were confirmed to be Mycobacterium leprae by by the National Hansen’s Disease program. Based on these findings, a diagnosis of lepromatous leprosy (LL) was made. The patient was treated by the infectious disease department with multidrug therapy that included monthly rifampin, moxifloxacin, and minocycline; weekly methotrexate with daily folic acid; and an extended prednisone taper with prophylactic cholecalciferol.

Lepromatous leprosy is characterized by high antibody titers to the acid-fast, gram-positive bacillus Mycobacterium leprae as well as a high bacillary load.¹ Patients typically present with muscle weakness, anesthetic skin patches, and claw hands. Patients also may present with foot drop, ulcerations of the hands and feet, autonomic dysfunction with anhidrosis or impaired sweating, and localized alopecia.² Over months to years, LL may progress to extensive sensory loss and indurated lesions that infiltrate the skin and cause thickening, especially on the face (known as leonine facies). Furthermore, LL is characterized by extensive bilaterally symmetric cutaneous lesions with poorly defined borders and raised indurated centers.³

Lepromatous leprosy transmission is not fully understood but is thought to occur via airborne droplets from coughing/sneezing and nasal secretions.² Histopathology generally shows a dense and diffuse granulomatous infiltrate that involves the dermis but is separated from the epidermis by a zone of collagen (grenz zone).³ Histology is characterized by the presence of lymphocytes and numerous foamy macrophages (lepra or Virchow cells) containing M leprae organisms. In persistent lesions, the high density of uncleared bacilli forms spherical cytoplasmic clumps known as globi within enlarged foamy histiocytes (Figure 1).⁴ The macrophages form granulomatous lesions in the skin and around nerve bundles, resulting in tissue damage and decreased sensation. The current standard of care for LL is a multidrug combination of dapsone, rifampin, and clofazimine. Early diagnosis and complete treatment of LL is crucial, as this approach typically leads to complete cure of the disease.

The differential diagnosis for LL includes granuloma annulare (GA), mycosis fungoides (MF), sarcoidosis, and subacute cutaneous lupus erythematosus (SCLE). Granuloma annulare is a noninfectious inflammatory granulomatous skin disease that manifests in a localized, generalized, or subcutaneous pattern. Localized GA is the most common form and manifests as self-resolving, flesh-colored or erythematous papules or plaques limited to the extremities.^5,6 Generalized GA is defined by more than 10 widespread annular plaques involving the trunk and extremities and can persist for decades.⁶ This form can be associated with hyperlipidemia, diabetes, autoimmune disease and immunodeficiency (eg, HIV), and rarely with lymphoma or solid tumors. On histology, GA shows necrobiosis surrounded by palisading histiocytes and mucin (palisading GA) or patchy interstitial histiocytes and lymphocytes (interstitial GA)(Figure 2).⁶ This palisading pattern differs from the histiocytes in LL, which contain numerous acid-fast bacilli and bacterial clumps. Topical and intralesional corticosteroids are first-line therapies for GA.

Mycosis fungoides is a cutaneous T-cell lymphoma characterized by proliferation of CD4+ T cells.⁷ In the early stages of MF, patients may present with multiple erythematous and scaly patches, plaques, or nodules that most commonly develop on unexposed areas of the skin, but specific variants frequently may cause lesions on the face or scalp.⁸ Tumors may be solitary, localized, or generalized and may be observed alongside patches and plaques or in the absence of cutaneous lesions.⁷ The pathologic features of MF include fibrosis of the papillary dermis, individual haloed atypical lymphocytes in the epidermis, and atypical lymphoid cells with cerebriform nuclei (Figure 3).⁹ Granulomatous MF is characterized by diffuse nodular and perivascular infiltrates of histiocytes with small lymphocytes without atypia, eosinophils, and plasma cells. Small lymphocytes with cerebriform nuclei and larger lymphocytes with hyperconvoluted nuclei also may be seen, in addition to multinucleated histiocytic giant cells. Although MF commonly manifests with epidermotropism, it typically is absent in granulomatous MF (GMF).¹⁰ Granulomatous MF may manifest similarly to LL. Noduloulcerative lesions and infiltration of atypical lymphocytes into the epidermis (epidermotropism) are much more common in GMF than in LL; however, although ulcerative nodules are not a common feature in patients with leprosy (except during reactional states [ie, Lucio phenomenon]) or secondary to neuropathies, they also can occur in LL.¹¹ In GMF, the infiltrate does not follow a specific pattern, whereas LL infiltrates tend to follow a nerve distribution. Treatment for MF is determined by disease severity.¹² First-line therapy includes local corticosteroids and phototherapy with UVB irradiation.

Sarcoidosis is a multisystem disease that demonstrates nonspecific clinical manifestations affecting the lungs, eyes, liver, and skin.¹³ Environmental exposures to silica and inorganic matter have been linked to an increased risk for sarcoidosis, with patients presenting with fatigue, fever, and arthralgia.¹³ Skin manifestations include subcutaneous nodules, polymorphous plaques, and erythema nodosum—nodosum—the most common cutaneous presentation of sarcoidosis. Erythema nodosum manifests as symmetrically distributed, nonulcerative, painful red nodules on the skin, especially the lower legs. The histopathology of sarcoidosis shows noncaseating granulomas with activated T-lymphocytes, epithelioid cells, and multinucleated giant cells (Figure 4). Although granulomas occur in both LL and sarcoidosis, those in sarcoidosis typically consist of epithelioid cells surrounded by a rim of lymphocytes, whereas LL granulomas contain foamy histiocytes and multinucleated giant cells. Treatment of sarcoidosis depends on disease progression and generally involves oral corticosteroids, followed by corticosteroid-sparing regimens.

Subacute cutaneous lupus erythematosus is a chronic autoimmune disease that predominantly affects younger women. Common findings in SCLE include red scaly plaques and ring-shaped lesions on sun-exposed areas of the skin.¹⁴ Subacute cutaneous lupus erythematosus primarily is characterized by a photosensitive rash, often with arthralgia, myalgia, and/or oral ulcers; less commonly, a small percentage of patients can experience central nervous system involvement, vasculitis, or nephritis. The histologic findings of SCLE include hydropic degeneration of the basal cell layer and periadnexal infiltrates (Figure 5). The incidence of SCLE often is associated with anti-Ro (SSA) and anti-La (SSB) antibodies.¹⁵ Treatment of SCLE focuses on managing skin symptoms with corticosteroids, antimalarials, and sun protection.

THE DIAGNOSIS: Lepromatous Leprosy

Histopathology showed collections of epithelioid to sarcoidal granulomas throughout the dermis and clustered around nerve bundles with a grenz zone at the dermoepidermal junction. Fite stain was positive for acid-fast bacteria, which were confirmed to be Mycobacterium leprae by by the National Hansen’s Disease program. Based on these findings, a diagnosis of lepromatous leprosy (LL) was made. The patient was treated by the infectious disease department with multidrug therapy that included monthly rifampin, moxifloxacin, and minocycline; weekly methotrexate with daily folic acid; and an extended prednisone taper with prophylactic cholecalciferol.

Lepromatous leprosy is characterized by high antibody titers to the acid-fast, gram-positive bacillus Mycobacterium leprae as well as a high bacillary load.¹ Patients typically present with muscle weakness, anesthetic skin patches, and claw hands. Patients also may present with foot drop, ulcerations of the hands and feet, autonomic dysfunction with anhidrosis or impaired sweating, and localized alopecia.² Over months to years, LL may progress to extensive sensory loss and indurated lesions that infiltrate the skin and cause thickening, especially on the face (known as leonine facies). Furthermore, LL is characterized by extensive bilaterally symmetric cutaneous lesions with poorly defined borders and raised indurated centers.³

Lepromatous leprosy transmission is not fully understood but is thought to occur via airborne droplets from coughing/sneezing and nasal secretions.² Histopathology generally shows a dense and diffuse granulomatous infiltrate that involves the dermis but is separated from the epidermis by a zone of collagen (grenz zone).³ Histology is characterized by the presence of lymphocytes and numerous foamy macrophages (lepra or Virchow cells) containing M leprae organisms. In persistent lesions, the high density of uncleared bacilli forms spherical cytoplasmic clumps known as globi within enlarged foamy histiocytes (Figure 1).⁴ The macrophages form granulomatous lesions in the skin and around nerve bundles, resulting in tissue damage and decreased sensation. The current standard of care for LL is a multidrug combination of dapsone, rifampin, and clofazimine. Early diagnosis and complete treatment of LL is crucial, as this approach typically leads to complete cure of the disease.

The differential diagnosis for LL includes granuloma annulare (GA), mycosis fungoides (MF), sarcoidosis, and subacute cutaneous lupus erythematosus (SCLE). Granuloma annulare is a noninfectious inflammatory granulomatous skin disease that manifests in a localized, generalized, or subcutaneous pattern. Localized GA is the most common form and manifests as self-resolving, flesh-colored or erythematous papules or plaques limited to the extremities.^5,6 Generalized GA is defined by more than 10 widespread annular plaques involving the trunk and extremities and can persist for decades.⁶ This form can be associated with hyperlipidemia, diabetes, autoimmune disease and immunodeficiency (eg, HIV), and rarely with lymphoma or solid tumors. On histology, GA shows necrobiosis surrounded by palisading histiocytes and mucin (palisading GA) or patchy interstitial histiocytes and lymphocytes (interstitial GA)(Figure 2).⁶ This palisading pattern differs from the histiocytes in LL, which contain numerous acid-fast bacilli and bacterial clumps. Topical and intralesional corticosteroids are first-line therapies for GA.

Mycosis fungoides is a cutaneous T-cell lymphoma characterized by proliferation of CD4+ T cells.⁷ In the early stages of MF, patients may present with multiple erythematous and scaly patches, plaques, or nodules that most commonly develop on unexposed areas of the skin, but specific variants frequently may cause lesions on the face or scalp.⁸ Tumors may be solitary, localized, or generalized and may be observed alongside patches and plaques or in the absence of cutaneous lesions.⁷ The pathologic features of MF include fibrosis of the papillary dermis, individual haloed atypical lymphocytes in the epidermis, and atypical lymphoid cells with cerebriform nuclei (Figure 3).⁹ Granulomatous MF is characterized by diffuse nodular and perivascular infiltrates of histiocytes with small lymphocytes without atypia, eosinophils, and plasma cells. Small lymphocytes with cerebriform nuclei and larger lymphocytes with hyperconvoluted nuclei also may be seen, in addition to multinucleated histiocytic giant cells. Although MF commonly manifests with epidermotropism, it typically is absent in granulomatous MF (GMF).¹⁰ Granulomatous MF may manifest similarly to LL. Noduloulcerative lesions and infiltration of atypical lymphocytes into the epidermis (epidermotropism) are much more common in GMF than in LL; however, although ulcerative nodules are not a common feature in patients with leprosy (except during reactional states [ie, Lucio phenomenon]) or secondary to neuropathies, they also can occur in LL.¹¹ In GMF, the infiltrate does not follow a specific pattern, whereas LL infiltrates tend to follow a nerve distribution. Treatment for MF is determined by disease severity.¹² First-line therapy includes local corticosteroids and phototherapy with UVB irradiation.

Sarcoidosis is a multisystem disease that demonstrates nonspecific clinical manifestations affecting the lungs, eyes, liver, and skin.¹³ Environmental exposures to silica and inorganic matter have been linked to an increased risk for sarcoidosis, with patients presenting with fatigue, fever, and arthralgia.¹³ Skin manifestations include subcutaneous nodules, polymorphous plaques, and erythema nodosum—nodosum—the most common cutaneous presentation of sarcoidosis. Erythema nodosum manifests as symmetrically distributed, nonulcerative, painful red nodules on the skin, especially the lower legs. The histopathology of sarcoidosis shows noncaseating granulomas with activated T-lymphocytes, epithelioid cells, and multinucleated giant cells (Figure 4). Although granulomas occur in both LL and sarcoidosis, those in sarcoidosis typically consist of epithelioid cells surrounded by a rim of lymphocytes, whereas LL granulomas contain foamy histiocytes and multinucleated giant cells. Treatment of sarcoidosis depends on disease progression and generally involves oral corticosteroids, followed by corticosteroid-sparing regimens.

Subacute cutaneous lupus erythematosus is a chronic autoimmune disease that predominantly affects younger women. Common findings in SCLE include red scaly plaques and ring-shaped lesions on sun-exposed areas of the skin.¹⁴ Subacute cutaneous lupus erythematosus primarily is characterized by a photosensitive rash, often with arthralgia, myalgia, and/or oral ulcers; less commonly, a small percentage of patients can experience central nervous system involvement, vasculitis, or nephritis. The histologic findings of SCLE include hydropic degeneration of the basal cell layer and periadnexal infiltrates (Figure 5). The incidence of SCLE often is associated with anti-Ro (SSA) and anti-La (SSB) antibodies.¹⁵ Treatment of SCLE focuses on managing skin symptoms with corticosteroids, antimalarials, and sun protection.

THE DIAGNOSIS: Lepromatous Leprosy

Histopathology showed collections of epithelioid to sarcoidal granulomas throughout the dermis and clustered around nerve bundles with a grenz zone at the dermoepidermal junction. Fite stain was positive for acid-fast bacteria, which were confirmed to be Mycobacterium leprae by by the National Hansen’s Disease program. Based on these findings, a diagnosis of lepromatous leprosy (LL) was made. The patient was treated by the infectious disease department with multidrug therapy that included monthly rifampin, moxifloxacin, and minocycline; weekly methotrexate with daily folic acid; and an extended prednisone taper with prophylactic cholecalciferol.

Lepromatous leprosy is characterized by high antibody titers to the acid-fast, gram-positive bacillus Mycobacterium leprae as well as a high bacillary load.¹ Patients typically present with muscle weakness, anesthetic skin patches, and claw hands. Patients also may present with foot drop, ulcerations of the hands and feet, autonomic dysfunction with anhidrosis or impaired sweating, and localized alopecia.² Over months to years, LL may progress to extensive sensory loss and indurated lesions that infiltrate the skin and cause thickening, especially on the face (known as leonine facies). Furthermore, LL is characterized by extensive bilaterally symmetric cutaneous lesions with poorly defined borders and raised indurated centers.³

Lepromatous leprosy transmission is not fully understood but is thought to occur via airborne droplets from coughing/sneezing and nasal secretions.² Histopathology generally shows a dense and diffuse granulomatous infiltrate that involves the dermis but is separated from the epidermis by a zone of collagen (grenz zone).³ Histology is characterized by the presence of lymphocytes and numerous foamy macrophages (lepra or Virchow cells) containing M leprae organisms. In persistent lesions, the high density of uncleared bacilli forms spherical cytoplasmic clumps known as globi within enlarged foamy histiocytes (Figure 1).⁴ The macrophages form granulomatous lesions in the skin and around nerve bundles, resulting in tissue damage and decreased sensation. The current standard of care for LL is a multidrug combination of dapsone, rifampin, and clofazimine. Early diagnosis and complete treatment of LL is crucial, as this approach typically leads to complete cure of the disease.

The differential diagnosis for LL includes granuloma annulare (GA), mycosis fungoides (MF), sarcoidosis, and subacute cutaneous lupus erythematosus (SCLE). Granuloma annulare is a noninfectious inflammatory granulomatous skin disease that manifests in a localized, generalized, or subcutaneous pattern. Localized GA is the most common form and manifests as self-resolving, flesh-colored or erythematous papules or plaques limited to the extremities.^5,6 Generalized GA is defined by more than 10 widespread annular plaques involving the trunk and extremities and can persist for decades.⁶ This form can be associated with hyperlipidemia, diabetes, autoimmune disease and immunodeficiency (eg, HIV), and rarely with lymphoma or solid tumors. On histology, GA shows necrobiosis surrounded by palisading histiocytes and mucin (palisading GA) or patchy interstitial histiocytes and lymphocytes (interstitial GA)(Figure 2).⁶ This palisading pattern differs from the histiocytes in LL, which contain numerous acid-fast bacilli and bacterial clumps. Topical and intralesional corticosteroids are first-line therapies for GA.

Mycosis fungoides is a cutaneous T-cell lymphoma characterized by proliferation of CD4+ T cells.⁷ In the early stages of MF, patients may present with multiple erythematous and scaly patches, plaques, or nodules that most commonly develop on unexposed areas of the skin, but specific variants frequently may cause lesions on the face or scalp.⁸ Tumors may be solitary, localized, or generalized and may be observed alongside patches and plaques or in the absence of cutaneous lesions.⁷ The pathologic features of MF include fibrosis of the papillary dermis, individual haloed atypical lymphocytes in the epidermis, and atypical lymphoid cells with cerebriform nuclei (Figure 3).⁹ Granulomatous MF is characterized by diffuse nodular and perivascular infiltrates of histiocytes with small lymphocytes without atypia, eosinophils, and plasma cells. Small lymphocytes with cerebriform nuclei and larger lymphocytes with hyperconvoluted nuclei also may be seen, in addition to multinucleated histiocytic giant cells. Although MF commonly manifests with epidermotropism, it typically is absent in granulomatous MF (GMF).¹⁰ Granulomatous MF may manifest similarly to LL. Noduloulcerative lesions and infiltration of atypical lymphocytes into the epidermis (epidermotropism) are much more common in GMF than in LL; however, although ulcerative nodules are not a common feature in patients with leprosy (except during reactional states [ie, Lucio phenomenon]) or secondary to neuropathies, they also can occur in LL.¹¹ In GMF, the infiltrate does not follow a specific pattern, whereas LL infiltrates tend to follow a nerve distribution. Treatment for MF is determined by disease severity.¹² First-line therapy includes local corticosteroids and phototherapy with UVB irradiation.

Sarcoidosis is a multisystem disease that demonstrates nonspecific clinical manifestations affecting the lungs, eyes, liver, and skin.¹³ Environmental exposures to silica and inorganic matter have been linked to an increased risk for sarcoidosis, with patients presenting with fatigue, fever, and arthralgia.¹³ Skin manifestations include subcutaneous nodules, polymorphous plaques, and erythema nodosum—nodosum—the most common cutaneous presentation of sarcoidosis. Erythema nodosum manifests as symmetrically distributed, nonulcerative, painful red nodules on the skin, especially the lower legs. The histopathology of sarcoidosis shows noncaseating granulomas with activated T-lymphocytes, epithelioid cells, and multinucleated giant cells (Figure 4). Although granulomas occur in both LL and sarcoidosis, those in sarcoidosis typically consist of epithelioid cells surrounded by a rim of lymphocytes, whereas LL granulomas contain foamy histiocytes and multinucleated giant cells. Treatment of sarcoidosis depends on disease progression and generally involves oral corticosteroids, followed by corticosteroid-sparing regimens.

Subacute cutaneous lupus erythematosus is a chronic autoimmune disease that predominantly affects younger women. Common findings in SCLE include red scaly plaques and ring-shaped lesions on sun-exposed areas of the skin.¹⁴ Subacute cutaneous lupus erythematosus primarily is characterized by a photosensitive rash, often with arthralgia, myalgia, and/or oral ulcers; less commonly, a small percentage of patients can experience central nervous system involvement, vasculitis, or nephritis. The histologic findings of SCLE include hydropic degeneration of the basal cell layer and periadnexal infiltrates (Figure 5). The incidence of SCLE often is associated with anti-Ro (SSA) and anti-La (SSB) antibodies.¹⁵ Treatment of SCLE focuses on managing skin symptoms with corticosteroids, antimalarials, and sun protection.

To the Editor:  

For many years, topical treatment of plaque psoriasis was limited to steroids, calcineurin inhibitors, vitamin D analogs, retinoids, coal tar products, and anthralin. In recent years, 2 new nonsteroidal treatment options with alternative mechanisms of action, roflumilast 0.3% and tapinarof 1%, have been approved by the US Food and Drug Administration.¹ Roflumilast 0.3%, a topical phosphodiesterase 4 inhibitor, was shown in phase 3 clinical trials to reach an Investigator Global Assessment response of 37.5% to 42.2% in 8 weeks using once-daily application with minimal cutaneous adverse effects.¹ Furthermore, it has demonstrated efficacy in treating psoriasis in intertriginous areas in subset analyses.¹ Tapinarof is an aryl hydrocarbon receptor agonist that suppresses Th17 cell differentiation by downregulating IL-17, IL-22, and IL-23.¹ In phase 3 clinical trials, 35% to 40% of patients who used tapinarof cream 1% once daily demonstrated improvement in psoriasis compared with 6% who used the vehicle alone.² In these studies, 18% to 24% of patients who used tapinarof cream 1% experienced folliculitis.²

Acute generalized exanthematous pustulosis (AGEP) is a nonfollicular pustular drug reaction with systemic symptoms that typically occurs within 2 weeks of exposure to an inciting medication. Systemic antibiotics are the most commonly reported cause of AGEP.³ There are few reports in the literature of AGEP induced by topical agents.^4,5 We report a case of AGEP in a young man following the use of tapinarof cream 1%.

A 23-year-old man with a history of psoriasis presented to the emergency department with fever and a pustular rash. One week prior to presentation, he developed a pustular eruption around plaques of psoriasis on the arms and legs. The patient had been prescribed tapinarof cream 1% by an outside dermatologist and was applying the medication to the affected areas once daily for 1 month prior to onset of symptoms. He discontinued tapinarof a few days prior to the eruption starting, but the rash progressed centrifugally and was associated with fevers and fatigue despite treatment with a brief course of empiric cephalexin prescribed by his primary care provider.

At presentation to our institution, the patient had widespread erythematous patches studded with pustules located on the arms, legs, and flexural areas as well as plaques of psoriasis involving approximately 20% of the body surface area (Figure 1). Furthermore, the patient was noted to have large noninflammatory bullae along the legs. The new eruption occurred on areas that were both treated and spared from the tapinarof cream 1%. Laboratory evaluation showed neutrophil-­predominant leukocytosis (white blood cell count, 15.9×10³/µL ­[reference range, 4.0-11.0×10³/µL]; absolute neutrophil count, 10.3×10³/µL [reference range, 1.5-8.0×10³/µL]), absolute eosinophilia (1930/µL [reference range, 0-0.5×10³/µL]), hypocalcemia (8.4 mg/dL ­[reference range, 8.5-10.5 mg/dL]), and a mild transaminitis ­(aspartate aminotransferase, 37 IU/L [reference range, 10-40 IU/L]; alanine aminotransferase, 53 IU/L ­[reference range, 7-56 U/L]). Histopathology demonstrated spongiosis with subcorneal and intraepidermal pustules and mixed dermal inflammation containing eosinophils (Figure 2). Direct immunofluorescence revealed mild granular staining of C3 at the basement membrane zone.

The patient was started on 1 mg/kg/d of prednisone tapered over 20 days, and he rapidly improved. Alanine aminotransferase levels peaked at 120 IU/L 2 weeks later. At that time, he had complete resolution of the original eruption and was transitioned to topical steroids for continued management of the psoriasis (Figure 3).

The differential diagnosis for our patient included AGEP, generalized pustular psoriasis (GPP), miliaria pustulosa, generalized cutaneous candidiasis, exuberant allergic contact dermatitis (ACD), and linear IgA bullous dermatosis (LABD). Based on the clinical manifestations, laboratory results, and histopathologic evaluation, we made the diagnosis of AGEP secondary to tapinarof with systemic absorption. Acute generalized exanthematous pustulosis has been reported with topical use of morphine and diphenhydramine, among other agents.^4,5 To our knowledge, AGEP due to tapinarof cream 1% has not been reported. In the original clinical trials of tapinarof, folliculitis was contained to sites of application.² Our patient developed pustules at sites distant to areas of application, as well as systemic symptoms and laboratory abnormalities, indicating a systemic reaction. It can be difficult to distinguish AGEP clinically and histologically from GPP. Both conditions can manifest with fever, hypocalcemia, and sterile pustules on a background of erythema that favors intertriginous areas.⁶ Infection, rapid oral steroid withdrawal, pregnancy, and rarely oral medications have been reported causes of GPP.⁶ Our patient did not have any of these exposures. There is overlap in the histology of AGEP and GPP. One retrospective series compared histologic samples to help distinguish these 2 entities. Reliable markers that favored AGEP over GPP included eosinophilic spongiosis, interface dermatitis, and dermal eosinophilia (>2/mm²).⁷ In contrast, the presence of CD161 positivity in the dermis with at least 10 cells favored a diagnosis of GPP.⁷ In our case, the presence of spongiosis with eosinophils in the dermis favored a diagnosis of AGEP over GPP. 

Miliaria pustulosa is a benign condition caused by the occlusion of the epidermal portion of eccrine glands related to either high fever or hot and humid environmental conditions. While it can be present in intertriginous areas like AGEP, miliaria pustulosa can be seen extensively on the back, most commonly in immobile hospitalized patients.⁸ Generalized cutaneous candidiasis usually is caused by the yeast Candida albicans and can take on multiple morphologies, including folliculitis.⁹ The eruption may be disseminated but often is accentuated in intertriginous areas and the anogenital folds. Predisposing factors include immunosuppression, endocrinopathies, recent use of systemic antibiotics or steroids, chemotherapy, and indwelling catheters.⁹ Outside of recent antibiotic use, our patient did not have any risk factors for miliaria pustulosa, making this diagnosis unlikely.

Given the presence of overlapping bullae along the lower extremities, an exuberant ACD and LABD were considered. Bullae formation can occur in ACD secondary to robust inflammation and edema leading to acantholysis.¹⁰ While a delayed hypersensitivity reaction to topical tapinarof cream 1% was considered given that the patient used the medication for approximately 1 month prior to the onset of symptoms, it would be unlikely for ACD to present with a concomitant pustular eruption. Linear IgA bullous dermatosis is an autoimmune blistering disease in which antibodies target bullous pemphigoid antigen 2, and there is characteristically linear deposition of IgA at the dermal-epidermal junction that leads to subepidermal blistering.¹¹ This often manifests clinically as widespread tense vesicles in an annular or string-of-pearls appearance. However, morphologies can vary, and large bullae may be seen. In adults, LABD typically is associated with inflammatory bowel disease, malignancy, or medications, notably vancomycin.^11,12 Our patient did not have any of these predisposing factors, and his biopsy for direct immunofluorescence did not reveal the classic pattern described above.

Interestingly, there have been reports in the literature of bullous AGEP in the setting of oral anti-infectives. One report described a 62-year-old woman who developed widespread nonfollicular pustules with multiple tense serous blisters 24 hours after taking oral terbinafine.¹³ Another case described an 80-year-old woman with a similar presentation following a course of ciprofloxacin (although the timeline of medication administration was not described).¹⁴ In this case, patch testing to the culprit medication reproduced the response.¹⁴ In both cases, a biopsy revealed subcorneal and intraepidermal pustules with marked dermal edema.^13,14 As previously described, spongiosis is a common feature of AGEP. We hypothesize that, similar to these reports, our patient had a robust inflammatory response leading to spongiosis, acantholysis, and blister formation secondary to AGEP.

Dermatologists should be aware of this case of AGEP secondary to tapinarof cream 1%, as reports in the literature are rare and it is a reminder that topical medications can cause serious systemic reactions.

To the Editor:  

For many years, topical treatment of plaque psoriasis was limited to steroids, calcineurin inhibitors, vitamin D analogs, retinoids, coal tar products, and anthralin. In recent years, 2 new nonsteroidal treatment options with alternative mechanisms of action, roflumilast 0.3% and tapinarof 1%, have been approved by the US Food and Drug Administration.¹ Roflumilast 0.3%, a topical phosphodiesterase 4 inhibitor, was shown in phase 3 clinical trials to reach an Investigator Global Assessment response of 37.5% to 42.2% in 8 weeks using once-daily application with minimal cutaneous adverse effects.¹ Furthermore, it has demonstrated efficacy in treating psoriasis in intertriginous areas in subset analyses.¹ Tapinarof is an aryl hydrocarbon receptor agonist that suppresses Th17 cell differentiation by downregulating IL-17, IL-22, and IL-23.¹ In phase 3 clinical trials, 35% to 40% of patients who used tapinarof cream 1% once daily demonstrated improvement in psoriasis compared with 6% who used the vehicle alone.² In these studies, 18% to 24% of patients who used tapinarof cream 1% experienced folliculitis.²

Acute generalized exanthematous pustulosis (AGEP) is a nonfollicular pustular drug reaction with systemic symptoms that typically occurs within 2 weeks of exposure to an inciting medication. Systemic antibiotics are the most commonly reported cause of AGEP.³ There are few reports in the literature of AGEP induced by topical agents.^4,5 We report a case of AGEP in a young man following the use of tapinarof cream 1%.

A 23-year-old man with a history of psoriasis presented to the emergency department with fever and a pustular rash. One week prior to presentation, he developed a pustular eruption around plaques of psoriasis on the arms and legs. The patient had been prescribed tapinarof cream 1% by an outside dermatologist and was applying the medication to the affected areas once daily for 1 month prior to onset of symptoms. He discontinued tapinarof a few days prior to the eruption starting, but the rash progressed centrifugally and was associated with fevers and fatigue despite treatment with a brief course of empiric cephalexin prescribed by his primary care provider.

At presentation to our institution, the patient had widespread erythematous patches studded with pustules located on the arms, legs, and flexural areas as well as plaques of psoriasis involving approximately 20% of the body surface area (Figure 1). Furthermore, the patient was noted to have large noninflammatory bullae along the legs. The new eruption occurred on areas that were both treated and spared from the tapinarof cream 1%. Laboratory evaluation showed neutrophil-­predominant leukocytosis (white blood cell count, 15.9×10³/µL ­[reference range, 4.0-11.0×10³/µL]; absolute neutrophil count, 10.3×10³/µL [reference range, 1.5-8.0×10³/µL]), absolute eosinophilia (1930/µL [reference range, 0-0.5×10³/µL]), hypocalcemia (8.4 mg/dL ­[reference range, 8.5-10.5 mg/dL]), and a mild transaminitis ­(aspartate aminotransferase, 37 IU/L [reference range, 10-40 IU/L]; alanine aminotransferase, 53 IU/L ­[reference range, 7-56 U/L]). Histopathology demonstrated spongiosis with subcorneal and intraepidermal pustules and mixed dermal inflammation containing eosinophils (Figure 2). Direct immunofluorescence revealed mild granular staining of C3 at the basement membrane zone.

The patient was started on 1 mg/kg/d of prednisone tapered over 20 days, and he rapidly improved. Alanine aminotransferase levels peaked at 120 IU/L 2 weeks later. At that time, he had complete resolution of the original eruption and was transitioned to topical steroids for continued management of the psoriasis (Figure 3).

The differential diagnosis for our patient included AGEP, generalized pustular psoriasis (GPP), miliaria pustulosa, generalized cutaneous candidiasis, exuberant allergic contact dermatitis (ACD), and linear IgA bullous dermatosis (LABD). Based on the clinical manifestations, laboratory results, and histopathologic evaluation, we made the diagnosis of AGEP secondary to tapinarof with systemic absorption. Acute generalized exanthematous pustulosis has been reported with topical use of morphine and diphenhydramine, among other agents.^4,5 To our knowledge, AGEP due to tapinarof cream 1% has not been reported. In the original clinical trials of tapinarof, folliculitis was contained to sites of application.² Our patient developed pustules at sites distant to areas of application, as well as systemic symptoms and laboratory abnormalities, indicating a systemic reaction. It can be difficult to distinguish AGEP clinically and histologically from GPP. Both conditions can manifest with fever, hypocalcemia, and sterile pustules on a background of erythema that favors intertriginous areas.⁶ Infection, rapid oral steroid withdrawal, pregnancy, and rarely oral medications have been reported causes of GPP.⁶ Our patient did not have any of these exposures. There is overlap in the histology of AGEP and GPP. One retrospective series compared histologic samples to help distinguish these 2 entities. Reliable markers that favored AGEP over GPP included eosinophilic spongiosis, interface dermatitis, and dermal eosinophilia (>2/mm²).⁷ In contrast, the presence of CD161 positivity in the dermis with at least 10 cells favored a diagnosis of GPP.⁷ In our case, the presence of spongiosis with eosinophils in the dermis favored a diagnosis of AGEP over GPP. 

Miliaria pustulosa is a benign condition caused by the occlusion of the epidermal portion of eccrine glands related to either high fever or hot and humid environmental conditions. While it can be present in intertriginous areas like AGEP, miliaria pustulosa can be seen extensively on the back, most commonly in immobile hospitalized patients.⁸ Generalized cutaneous candidiasis usually is caused by the yeast Candida albicans and can take on multiple morphologies, including folliculitis.⁹ The eruption may be disseminated but often is accentuated in intertriginous areas and the anogenital folds. Predisposing factors include immunosuppression, endocrinopathies, recent use of systemic antibiotics or steroids, chemotherapy, and indwelling catheters.⁹ Outside of recent antibiotic use, our patient did not have any risk factors for miliaria pustulosa, making this diagnosis unlikely.

Given the presence of overlapping bullae along the lower extremities, an exuberant ACD and LABD were considered. Bullae formation can occur in ACD secondary to robust inflammation and edema leading to acantholysis.¹⁰ While a delayed hypersensitivity reaction to topical tapinarof cream 1% was considered given that the patient used the medication for approximately 1 month prior to the onset of symptoms, it would be unlikely for ACD to present with a concomitant pustular eruption. Linear IgA bullous dermatosis is an autoimmune blistering disease in which antibodies target bullous pemphigoid antigen 2, and there is characteristically linear deposition of IgA at the dermal-epidermal junction that leads to subepidermal blistering.¹¹ This often manifests clinically as widespread tense vesicles in an annular or string-of-pearls appearance. However, morphologies can vary, and large bullae may be seen. In adults, LABD typically is associated with inflammatory bowel disease, malignancy, or medications, notably vancomycin.^11,12 Our patient did not have any of these predisposing factors, and his biopsy for direct immunofluorescence did not reveal the classic pattern described above.

Interestingly, there have been reports in the literature of bullous AGEP in the setting of oral anti-infectives. One report described a 62-year-old woman who developed widespread nonfollicular pustules with multiple tense serous blisters 24 hours after taking oral terbinafine.¹³ Another case described an 80-year-old woman with a similar presentation following a course of ciprofloxacin (although the timeline of medication administration was not described).¹⁴ In this case, patch testing to the culprit medication reproduced the response.¹⁴ In both cases, a biopsy revealed subcorneal and intraepidermal pustules with marked dermal edema.^13,14 As previously described, spongiosis is a common feature of AGEP. We hypothesize that, similar to these reports, our patient had a robust inflammatory response leading to spongiosis, acantholysis, and blister formation secondary to AGEP.

Dermatologists should be aware of this case of AGEP secondary to tapinarof cream 1%, as reports in the literature are rare and it is a reminder that topical medications can cause serious systemic reactions.

To the Editor:  

For many years, topical treatment of plaque psoriasis was limited to steroids, calcineurin inhibitors, vitamin D analogs, retinoids, coal tar products, and anthralin. In recent years, 2 new nonsteroidal treatment options with alternative mechanisms of action, roflumilast 0.3% and tapinarof 1%, have been approved by the US Food and Drug Administration.¹ Roflumilast 0.3%, a topical phosphodiesterase 4 inhibitor, was shown in phase 3 clinical trials to reach an Investigator Global Assessment response of 37.5% to 42.2% in 8 weeks using once-daily application with minimal cutaneous adverse effects.¹ Furthermore, it has demonstrated efficacy in treating psoriasis in intertriginous areas in subset analyses.¹ Tapinarof is an aryl hydrocarbon receptor agonist that suppresses Th17 cell differentiation by downregulating IL-17, IL-22, and IL-23.¹ In phase 3 clinical trials, 35% to 40% of patients who used tapinarof cream 1% once daily demonstrated improvement in psoriasis compared with 6% who used the vehicle alone.² In these studies, 18% to 24% of patients who used tapinarof cream 1% experienced folliculitis.²

Acute generalized exanthematous pustulosis (AGEP) is a nonfollicular pustular drug reaction with systemic symptoms that typically occurs within 2 weeks of exposure to an inciting medication. Systemic antibiotics are the most commonly reported cause of AGEP.³ There are few reports in the literature of AGEP induced by topical agents.^4,5 We report a case of AGEP in a young man following the use of tapinarof cream 1%.

A 23-year-old man with a history of psoriasis presented to the emergency department with fever and a pustular rash. One week prior to presentation, he developed a pustular eruption around plaques of psoriasis on the arms and legs. The patient had been prescribed tapinarof cream 1% by an outside dermatologist and was applying the medication to the affected areas once daily for 1 month prior to onset of symptoms. He discontinued tapinarof a few days prior to the eruption starting, but the rash progressed centrifugally and was associated with fevers and fatigue despite treatment with a brief course of empiric cephalexin prescribed by his primary care provider.

At presentation to our institution, the patient had widespread erythematous patches studded with pustules located on the arms, legs, and flexural areas as well as plaques of psoriasis involving approximately 20% of the body surface area (Figure 1). Furthermore, the patient was noted to have large noninflammatory bullae along the legs. The new eruption occurred on areas that were both treated and spared from the tapinarof cream 1%. Laboratory evaluation showed neutrophil-­predominant leukocytosis (white blood cell count, 15.9×10³/µL ­[reference range, 4.0-11.0×10³/µL]; absolute neutrophil count, 10.3×10³/µL [reference range, 1.5-8.0×10³/µL]), absolute eosinophilia (1930/µL [reference range, 0-0.5×10³/µL]), hypocalcemia (8.4 mg/dL ­[reference range, 8.5-10.5 mg/dL]), and a mild transaminitis ­(aspartate aminotransferase, 37 IU/L [reference range, 10-40 IU/L]; alanine aminotransferase, 53 IU/L ­[reference range, 7-56 U/L]). Histopathology demonstrated spongiosis with subcorneal and intraepidermal pustules and mixed dermal inflammation containing eosinophils (Figure 2). Direct immunofluorescence revealed mild granular staining of C3 at the basement membrane zone.

The patient was started on 1 mg/kg/d of prednisone tapered over 20 days, and he rapidly improved. Alanine aminotransferase levels peaked at 120 IU/L 2 weeks later. At that time, he had complete resolution of the original eruption and was transitioned to topical steroids for continued management of the psoriasis (Figure 3).

The differential diagnosis for our patient included AGEP, generalized pustular psoriasis (GPP), miliaria pustulosa, generalized cutaneous candidiasis, exuberant allergic contact dermatitis (ACD), and linear IgA bullous dermatosis (LABD). Based on the clinical manifestations, laboratory results, and histopathologic evaluation, we made the diagnosis of AGEP secondary to tapinarof with systemic absorption. Acute generalized exanthematous pustulosis has been reported with topical use of morphine and diphenhydramine, among other agents.^4,5 To our knowledge, AGEP due to tapinarof cream 1% has not been reported. In the original clinical trials of tapinarof, folliculitis was contained to sites of application.² Our patient developed pustules at sites distant to areas of application, as well as systemic symptoms and laboratory abnormalities, indicating a systemic reaction. It can be difficult to distinguish AGEP clinically and histologically from GPP. Both conditions can manifest with fever, hypocalcemia, and sterile pustules on a background of erythema that favors intertriginous areas.⁶ Infection, rapid oral steroid withdrawal, pregnancy, and rarely oral medications have been reported causes of GPP.⁶ Our patient did not have any of these exposures. There is overlap in the histology of AGEP and GPP. One retrospective series compared histologic samples to help distinguish these 2 entities. Reliable markers that favored AGEP over GPP included eosinophilic spongiosis, interface dermatitis, and dermal eosinophilia (>2/mm²).⁷ In contrast, the presence of CD161 positivity in the dermis with at least 10 cells favored a diagnosis of GPP.⁷ In our case, the presence of spongiosis with eosinophils in the dermis favored a diagnosis of AGEP over GPP. 

Miliaria pustulosa is a benign condition caused by the occlusion of the epidermal portion of eccrine glands related to either high fever or hot and humid environmental conditions. While it can be present in intertriginous areas like AGEP, miliaria pustulosa can be seen extensively on the back, most commonly in immobile hospitalized patients.⁸ Generalized cutaneous candidiasis usually is caused by the yeast Candida albicans and can take on multiple morphologies, including folliculitis.⁹ The eruption may be disseminated but often is accentuated in intertriginous areas and the anogenital folds. Predisposing factors include immunosuppression, endocrinopathies, recent use of systemic antibiotics or steroids, chemotherapy, and indwelling catheters.⁹ Outside of recent antibiotic use, our patient did not have any risk factors for miliaria pustulosa, making this diagnosis unlikely.

Given the presence of overlapping bullae along the lower extremities, an exuberant ACD and LABD were considered. Bullae formation can occur in ACD secondary to robust inflammation and edema leading to acantholysis.¹⁰ While a delayed hypersensitivity reaction to topical tapinarof cream 1% was considered given that the patient used the medication for approximately 1 month prior to the onset of symptoms, it would be unlikely for ACD to present with a concomitant pustular eruption. Linear IgA bullous dermatosis is an autoimmune blistering disease in which antibodies target bullous pemphigoid antigen 2, and there is characteristically linear deposition of IgA at the dermal-epidermal junction that leads to subepidermal blistering.¹¹ This often manifests clinically as widespread tense vesicles in an annular or string-of-pearls appearance. However, morphologies can vary, and large bullae may be seen. In adults, LABD typically is associated with inflammatory bowel disease, malignancy, or medications, notably vancomycin.^11,12 Our patient did not have any of these predisposing factors, and his biopsy for direct immunofluorescence did not reveal the classic pattern described above.

Interestingly, there have been reports in the literature of bullous AGEP in the setting of oral anti-infectives. One report described a 62-year-old woman who developed widespread nonfollicular pustules with multiple tense serous blisters 24 hours after taking oral terbinafine.¹³ Another case described an 80-year-old woman with a similar presentation following a course of ciprofloxacin (although the timeline of medication administration was not described).¹⁴ In this case, patch testing to the culprit medication reproduced the response.¹⁴ In both cases, a biopsy revealed subcorneal and intraepidermal pustules with marked dermal edema.^13,14 As previously described, spongiosis is a common feature of AGEP. We hypothesize that, similar to these reports, our patient had a robust inflammatory response leading to spongiosis, acantholysis, and blister formation secondary to AGEP.

Dermatologists should be aware of this case of AGEP secondary to tapinarof cream 1%, as reports in the literature are rare and it is a reminder that topical medications can cause serious systemic reactions.

The Diagnosis: Glomangiomyoma

The nail unit excision specimen showed collections of cuboidal cells and spindled cells within the corium that were consistent with a diagnosis of a glomangiomyoma, a rare glomus tumor variant (Figure). Glomus tumors are benign neoplasms comprising glomus bodies, which are arteriovenous anastomoses involved in thermoregulation.¹ They develop in areas densely populated by glomus bodies, including the fingers, toes, and subungual areas. Glomus tumors most commonly develop in middle-aged women.² Clinically, they manifest with a characteristic triad of intense pain, point tenderness, and cold sensitivity and may appear as reddish-pink or blue macules under the nail plate and/or longitudinal erythronychia.^2-6 The presence of multiple glomus tumors is associated with neurofibromatosis type 1.⁷ 

Advanced imaging including ultrasonography and magnetic resonance imaging (MRI) may help confirm the diagnosis but may not be cost effective, as excision with histopathology is needed to relieve symptoms and render a definitive diagnosis. Radiography is highly insensitive in identifying bone erosions associated with glomus tumors.⁸ With ultrasonography, glomus tumors appear hypoechoic; with Doppler ultrasonography, they appear hypervascular. With MRI, glomus tumors appear as well-defined nodular lesions with hypointense signal intensity on T1-weighted sequence and hyperintense signal intensity on T2-weighted sequence, with strong enhancement using gadolinium-based contrast.^9,10 On histopathology, a glomus tumor appears as a nodular tumor with sheets of oval-nucleated cells arranged in multicellular layers surrounding blood vessels and are immunoreactive for α-smooth muscle actin, muscle-specific actin, and type IV collagen.^11,12 

There are several glomus tumor variants. The most common is a solid glomus tumor, which predominantly is composed of glomus cells, followed by glomangioma, which mainly is composed of blood vessels. Glomangiomyoma, which mostly is composed of smooth muscle cells, is the rarest variant.¹³ 

While glomus tumors are common in the subungual areas, it is an uncommon location for glomangiomyomas, which have been reported in the nail unit in only 7 prior case reports identified through searches of PubMed and Google Scholar using the terms glomangiomyoma, glomangiomyoma nail, and subungual glomangiomyoma (Table).^13-19 Glomangiomyomas more commonly are described in solid organs, including the stomach, kidney, pancreas, and bladder.¹⁶ The mean age of patients with subungual glomangiomyomas, including our patient, was 40.4 years (range, 3-61 years), with the majority being female (75.0% [6/8]). Most patients presented with fingernail involvement (75.0% [6/8]), nail dystrophy (eg, nail plate thinning, longitudinal grooves, splinter hemorrhages, longitudinal erythronychia)(62.5% [5/8]), and intermittent pain and/or point tenderness in the affected nail (75.0% [6/8]).^13-19 Notably, only our patient had longitudinal erythronychia as a clinical feature, and only one other case described MRI findings, which included a lobulated mass with intense contrast and distal phalanx destruction.¹⁸ One patient was a 3-year-old girl with a family history of generalized multiple glomangiomyomas. Although subungual glomangiomyoma was not confirmed on histopathology, the diagnosis in this patient was presumed based on her family history.¹³ On histopathology, glomangiomyomas are composed of oval-nucleated cells surrounding blood vessels. These oval-nucleated cells then gradually transition to smooth muscle cells.²⁰ 

A myxoid cyst is composed of a pseudocyst, which lacks a cyst lining, and is a result of synovial fluid from the distal interphalangeal joint entering the pseudocyst space.² It typically manifests with a longitudinal groove in the nail plate. A flesh-colored nodule may be appreciated between the cuticle and the distal interphalangeal joint.² The depth of the longitudinal groove may vary depending on the volume of synovial fluid within the myxoid cyst.²¹ In a series of 35 cases of subungual myxoid cysts, none manifested with longitudinal erythronychia. Due to their composition, myxoid cysts can be distinguished easily from solid tumors of the nail unit via transillumination.²² Pain is a much less common with myxoid cysts vs glomus tumors, as the filling of the pseudocyst space with synovial fluid typically is gradual, allowing the surrounding tissue to accommodate and adapt over time.²¹ In equivocal cases, MRI or high-resolution ultrasonography may be used to distinguish myxoid cysts and glomus tumors.⁸ Histopathology shows accumulation of mucin in the dermis with surrounding fibrous stroma.²³

Subungual neuromas are painful benign tumors that develop due to disorganized neural proliferation following disruption to peripheral nerves secondary to trauma or surgery. In 3 case reports, subungual neuromas manifested as painful subungual nodules, with proximal nail plate ridging, or onycholysis.^24-26 Since neuromas have only rarely been described in the subungual region, reports of MRI and ultrasonography findings are unknown. Histopathology is needed to distinguish neuromas from glomus tumors. Histopathology shows an acapsular structure consisting of disorganized spindle-cell proliferation and nerve fibers arranged in a tangle of fascicles within fibrotic tissue.²⁵ On immunochemistry, spindle cells typically are positive for cellular antigen protein S100.²⁶ 

Leiomyomas are benign neoplasms derived from smooth muscle, typically localized to the uterus or gastrointestinal tract, and have been described rarely in the nail unit.^27,28 It is hypothesized that subungual leiomyomas originate from the vascular smooth muscle in the subcutaneous layer of the nail unit.²⁸ Like glomus tumors, leiomyomas of the subungual region often manifest with pain and longitudinal erythronychia.^27-30 Subungual leiomyomas may be distinguished from glomus tumors via advanced imaging techniques, including ultrasonography and MRI. Cutaneous leiomyomas have been described with mild to moderate internal low flow vascularity on Doppler ultrasonography, while glomus tumors typically reveal high internal vascularity.²⁸ Biopsy with histopathology is needed for definitive diagnosis. On histopathology, leiomyomas demonstrate bland-appearing spindle-shaped cells with elongated nuclei arranged in fascicles.²⁷ They typically are positive for α-smooth muscle actin and caldesmon on immunostaining. 

Eccrine spiradenomas are benign adnexal tumors likely of apocrine origin with limited case reports in the literature.^31,32 Clinically, eccrine spiradenomas involving the nail unit may manifest with longitudinal nail splitting of the nail or as a papule on the proximal nail fold, with associated tenderness.^31,32 In a report of a 50-year-old woman with a histopathologically confirmed eccrine spiradenoma manifesting with longitudinal splitting of the nail and pain in the proximal nail fold, the mass appeared hypoechoic on ultrasonography with increased intramass vascularity on Doppler, while MRI showed an intensely enhancing lesion.³¹ These imaging features, combined with a classically manifesting feature of pain, make eccrine spiradenomas difficult to distinguish from glomus tumors; therefore, histopathologic examination can provide a definitive diagnosis, and surgical excision is used for treatment.³¹ On histopathology, these tumors are well circumscribed and composed of both small dark basaloid cells with peripheral compact nuclei and larger cells with central pale nuclei, which may be arranged in tubules.^31,32

The Diagnosis: Glomangiomyoma

The nail unit excision specimen showed collections of cuboidal cells and spindled cells within the corium that were consistent with a diagnosis of a glomangiomyoma, a rare glomus tumor variant (Figure). Glomus tumors are benign neoplasms comprising glomus bodies, which are arteriovenous anastomoses involved in thermoregulation.¹ They develop in areas densely populated by glomus bodies, including the fingers, toes, and subungual areas. Glomus tumors most commonly develop in middle-aged women.² Clinically, they manifest with a characteristic triad of intense pain, point tenderness, and cold sensitivity and may appear as reddish-pink or blue macules under the nail plate and/or longitudinal erythronychia.^2-6 The presence of multiple glomus tumors is associated with neurofibromatosis type 1.⁷ 

Advanced imaging including ultrasonography and magnetic resonance imaging (MRI) may help confirm the diagnosis but may not be cost effective, as excision with histopathology is needed to relieve symptoms and render a definitive diagnosis. Radiography is highly insensitive in identifying bone erosions associated with glomus tumors.⁸ With ultrasonography, glomus tumors appear hypoechoic; with Doppler ultrasonography, they appear hypervascular. With MRI, glomus tumors appear as well-defined nodular lesions with hypointense signal intensity on T1-weighted sequence and hyperintense signal intensity on T2-weighted sequence, with strong enhancement using gadolinium-based contrast.^9,10 On histopathology, a glomus tumor appears as a nodular tumor with sheets of oval-nucleated cells arranged in multicellular layers surrounding blood vessels and are immunoreactive for α-smooth muscle actin, muscle-specific actin, and type IV collagen.^11,12 

There are several glomus tumor variants. The most common is a solid glomus tumor, which predominantly is composed of glomus cells, followed by glomangioma, which mainly is composed of blood vessels. Glomangiomyoma, which mostly is composed of smooth muscle cells, is the rarest variant.¹³ 

While glomus tumors are common in the subungual areas, it is an uncommon location for glomangiomyomas, which have been reported in the nail unit in only 7 prior case reports identified through searches of PubMed and Google Scholar using the terms glomangiomyoma, glomangiomyoma nail, and subungual glomangiomyoma (Table).^13-19 Glomangiomyomas more commonly are described in solid organs, including the stomach, kidney, pancreas, and bladder.¹⁶ The mean age of patients with subungual glomangiomyomas, including our patient, was 40.4 years (range, 3-61 years), with the majority being female (75.0% [6/8]). Most patients presented with fingernail involvement (75.0% [6/8]), nail dystrophy (eg, nail plate thinning, longitudinal grooves, splinter hemorrhages, longitudinal erythronychia)(62.5% [5/8]), and intermittent pain and/or point tenderness in the affected nail (75.0% [6/8]).^13-19 Notably, only our patient had longitudinal erythronychia as a clinical feature, and only one other case described MRI findings, which included a lobulated mass with intense contrast and distal phalanx destruction.¹⁸ One patient was a 3-year-old girl with a family history of generalized multiple glomangiomyomas. Although subungual glomangiomyoma was not confirmed on histopathology, the diagnosis in this patient was presumed based on her family history.¹³ On histopathology, glomangiomyomas are composed of oval-nucleated cells surrounding blood vessels. These oval-nucleated cells then gradually transition to smooth muscle cells.²⁰ 

A myxoid cyst is composed of a pseudocyst, which lacks a cyst lining, and is a result of synovial fluid from the distal interphalangeal joint entering the pseudocyst space.² It typically manifests with a longitudinal groove in the nail plate. A flesh-colored nodule may be appreciated between the cuticle and the distal interphalangeal joint.² The depth of the longitudinal groove may vary depending on the volume of synovial fluid within the myxoid cyst.²¹ In a series of 35 cases of subungual myxoid cysts, none manifested with longitudinal erythronychia. Due to their composition, myxoid cysts can be distinguished easily from solid tumors of the nail unit via transillumination.²² Pain is a much less common with myxoid cysts vs glomus tumors, as the filling of the pseudocyst space with synovial fluid typically is gradual, allowing the surrounding tissue to accommodate and adapt over time.²¹ In equivocal cases, MRI or high-resolution ultrasonography may be used to distinguish myxoid cysts and glomus tumors.⁸ Histopathology shows accumulation of mucin in the dermis with surrounding fibrous stroma.²³

Subungual neuromas are painful benign tumors that develop due to disorganized neural proliferation following disruption to peripheral nerves secondary to trauma or surgery. In 3 case reports, subungual neuromas manifested as painful subungual nodules, with proximal nail plate ridging, or onycholysis.^24-26 Since neuromas have only rarely been described in the subungual region, reports of MRI and ultrasonography findings are unknown. Histopathology is needed to distinguish neuromas from glomus tumors. Histopathology shows an acapsular structure consisting of disorganized spindle-cell proliferation and nerve fibers arranged in a tangle of fascicles within fibrotic tissue.²⁵ On immunochemistry, spindle cells typically are positive for cellular antigen protein S100.²⁶ 

Leiomyomas are benign neoplasms derived from smooth muscle, typically localized to the uterus or gastrointestinal tract, and have been described rarely in the nail unit.^27,28 It is hypothesized that subungual leiomyomas originate from the vascular smooth muscle in the subcutaneous layer of the nail unit.²⁸ Like glomus tumors, leiomyomas of the subungual region often manifest with pain and longitudinal erythronychia.^27-30 Subungual leiomyomas may be distinguished from glomus tumors via advanced imaging techniques, including ultrasonography and MRI. Cutaneous leiomyomas have been described with mild to moderate internal low flow vascularity on Doppler ultrasonography, while glomus tumors typically reveal high internal vascularity.²⁸ Biopsy with histopathology is needed for definitive diagnosis. On histopathology, leiomyomas demonstrate bland-appearing spindle-shaped cells with elongated nuclei arranged in fascicles.²⁷ They typically are positive for α-smooth muscle actin and caldesmon on immunostaining. 

Eccrine spiradenomas are benign adnexal tumors likely of apocrine origin with limited case reports in the literature.^31,32 Clinically, eccrine spiradenomas involving the nail unit may manifest with longitudinal nail splitting of the nail or as a papule on the proximal nail fold, with associated tenderness.^31,32 In a report of a 50-year-old woman with a histopathologically confirmed eccrine spiradenoma manifesting with longitudinal splitting of the nail and pain in the proximal nail fold, the mass appeared hypoechoic on ultrasonography with increased intramass vascularity on Doppler, while MRI showed an intensely enhancing lesion.³¹ These imaging features, combined with a classically manifesting feature of pain, make eccrine spiradenomas difficult to distinguish from glomus tumors; therefore, histopathologic examination can provide a definitive diagnosis, and surgical excision is used for treatment.³¹ On histopathology, these tumors are well circumscribed and composed of both small dark basaloid cells with peripheral compact nuclei and larger cells with central pale nuclei, which may be arranged in tubules.^31,32

The Diagnosis: Glomangiomyoma

The nail unit excision specimen showed collections of cuboidal cells and spindled cells within the corium that were consistent with a diagnosis of a glomangiomyoma, a rare glomus tumor variant (Figure). Glomus tumors are benign neoplasms comprising glomus bodies, which are arteriovenous anastomoses involved in thermoregulation.¹ They develop in areas densely populated by glomus bodies, including the fingers, toes, and subungual areas. Glomus tumors most commonly develop in middle-aged women.² Clinically, they manifest with a characteristic triad of intense pain, point tenderness, and cold sensitivity and may appear as reddish-pink or blue macules under the nail plate and/or longitudinal erythronychia.^2-6 The presence of multiple glomus tumors is associated with neurofibromatosis type 1.⁷ 

Advanced imaging including ultrasonography and magnetic resonance imaging (MRI) may help confirm the diagnosis but may not be cost effective, as excision with histopathology is needed to relieve symptoms and render a definitive diagnosis. Radiography is highly insensitive in identifying bone erosions associated with glomus tumors.⁸ With ultrasonography, glomus tumors appear hypoechoic; with Doppler ultrasonography, they appear hypervascular. With MRI, glomus tumors appear as well-defined nodular lesions with hypointense signal intensity on T1-weighted sequence and hyperintense signal intensity on T2-weighted sequence, with strong enhancement using gadolinium-based contrast.^9,10 On histopathology, a glomus tumor appears as a nodular tumor with sheets of oval-nucleated cells arranged in multicellular layers surrounding blood vessels and are immunoreactive for α-smooth muscle actin, muscle-specific actin, and type IV collagen.^11,12 

There are several glomus tumor variants. The most common is a solid glomus tumor, which predominantly is composed of glomus cells, followed by glomangioma, which mainly is composed of blood vessels. Glomangiomyoma, which mostly is composed of smooth muscle cells, is the rarest variant.¹³ 

While glomus tumors are common in the subungual areas, it is an uncommon location for glomangiomyomas, which have been reported in the nail unit in only 7 prior case reports identified through searches of PubMed and Google Scholar using the terms glomangiomyoma, glomangiomyoma nail, and subungual glomangiomyoma (Table).^13-19 Glomangiomyomas more commonly are described in solid organs, including the stomach, kidney, pancreas, and bladder.¹⁶ The mean age of patients with subungual glomangiomyomas, including our patient, was 40.4 years (range, 3-61 years), with the majority being female (75.0% [6/8]). Most patients presented with fingernail involvement (75.0% [6/8]), nail dystrophy (eg, nail plate thinning, longitudinal grooves, splinter hemorrhages, longitudinal erythronychia)(62.5% [5/8]), and intermittent pain and/or point tenderness in the affected nail (75.0% [6/8]).^13-19 Notably, only our patient had longitudinal erythronychia as a clinical feature, and only one other case described MRI findings, which included a lobulated mass with intense contrast and distal phalanx destruction.¹⁸ One patient was a 3-year-old girl with a family history of generalized multiple glomangiomyomas. Although subungual glomangiomyoma was not confirmed on histopathology, the diagnosis in this patient was presumed based on her family history.¹³ On histopathology, glomangiomyomas are composed of oval-nucleated cells surrounding blood vessels. These oval-nucleated cells then gradually transition to smooth muscle cells.²⁰ 

A myxoid cyst is composed of a pseudocyst, which lacks a cyst lining, and is a result of synovial fluid from the distal interphalangeal joint entering the pseudocyst space.² It typically manifests with a longitudinal groove in the nail plate. A flesh-colored nodule may be appreciated between the cuticle and the distal interphalangeal joint.² The depth of the longitudinal groove may vary depending on the volume of synovial fluid within the myxoid cyst.²¹ In a series of 35 cases of subungual myxoid cysts, none manifested with longitudinal erythronychia. Due to their composition, myxoid cysts can be distinguished easily from solid tumors of the nail unit via transillumination.²² Pain is a much less common with myxoid cysts vs glomus tumors, as the filling of the pseudocyst space with synovial fluid typically is gradual, allowing the surrounding tissue to accommodate and adapt over time.²¹ In equivocal cases, MRI or high-resolution ultrasonography may be used to distinguish myxoid cysts and glomus tumors.⁸ Histopathology shows accumulation of mucin in the dermis with surrounding fibrous stroma.²³

Subungual neuromas are painful benign tumors that develop due to disorganized neural proliferation following disruption to peripheral nerves secondary to trauma or surgery. In 3 case reports, subungual neuromas manifested as painful subungual nodules, with proximal nail plate ridging, or onycholysis.^24-26 Since neuromas have only rarely been described in the subungual region, reports of MRI and ultrasonography findings are unknown. Histopathology is needed to distinguish neuromas from glomus tumors. Histopathology shows an acapsular structure consisting of disorganized spindle-cell proliferation and nerve fibers arranged in a tangle of fascicles within fibrotic tissue.²⁵ On immunochemistry, spindle cells typically are positive for cellular antigen protein S100.²⁶ 

Leiomyomas are benign neoplasms derived from smooth muscle, typically localized to the uterus or gastrointestinal tract, and have been described rarely in the nail unit.^27,28 It is hypothesized that subungual leiomyomas originate from the vascular smooth muscle in the subcutaneous layer of the nail unit.²⁸ Like glomus tumors, leiomyomas of the subungual region often manifest with pain and longitudinal erythronychia.^27-30 Subungual leiomyomas may be distinguished from glomus tumors via advanced imaging techniques, including ultrasonography and MRI. Cutaneous leiomyomas have been described with mild to moderate internal low flow vascularity on Doppler ultrasonography, while glomus tumors typically reveal high internal vascularity.²⁸ Biopsy with histopathology is needed for definitive diagnosis. On histopathology, leiomyomas demonstrate bland-appearing spindle-shaped cells with elongated nuclei arranged in fascicles.²⁷ They typically are positive for α-smooth muscle actin and caldesmon on immunostaining. 

Eccrine spiradenomas are benign adnexal tumors likely of apocrine origin with limited case reports in the literature.^31,32 Clinically, eccrine spiradenomas involving the nail unit may manifest with longitudinal nail splitting of the nail or as a papule on the proximal nail fold, with associated tenderness.^31,32 In a report of a 50-year-old woman with a histopathologically confirmed eccrine spiradenoma manifesting with longitudinal splitting of the nail and pain in the proximal nail fold, the mass appeared hypoechoic on ultrasonography with increased intramass vascularity on Doppler, while MRI showed an intensely enhancing lesion.³¹ These imaging features, combined with a classically manifesting feature of pain, make eccrine spiradenomas difficult to distinguish from glomus tumors; therefore, histopathologic examination can provide a definitive diagnosis, and surgical excision is used for treatment.³¹ On histopathology, these tumors are well circumscribed and composed of both small dark basaloid cells with peripheral compact nuclei and larger cells with central pale nuclei, which may be arranged in tubules.^31,32

The requisites of government are that there be sufficiency of food, sufficiency of military equipment, and the confidence of the people in their ruler.

Analects by Confucius¹

From ancient festivals to modern holidays, autumn has long been associated with the gathering of the harvest. Friends and families come together around tables laden with delicious food to enjoy the pleasures of peace and plenty. During these celebrations, we must never forget that without the strength of the nation’s military and the service of its veterans, this freedom and abundance would not be possible. Our debt of gratitude to the current and former members of the armed services makes the fact that a substantial minority experiences food insecurity not only a human tragedy, but a travesty of the nation’s promise to support those who wear or have worn the uniform.

The National Defense Authorization Act for Fiscal Year 2020 charged the Secretary of Defense to investigate food insecurity among active-duty service members and their dependents.² The RAND Corporation conducted the assessment and, based on the results of its analysis, made recommendations to reduce hunger among armed forces members and their families.³

The RAND study found that 10% of active-duty military met US Department of Agriculture (USDA) criteria for very low food security; another 15% were classified as having low food security. The USDA defines food insecurity with hunger as “reports of multiple indications of disrupted eating patterns and reduced food intake.” USDA defines low food security as “reports of reduced quality, variety, or desirability of diet. Little or no indication of reduced food intake.”⁴

As someone who grew up on an Army base with the commissary a short trip from military housing, I was unpleasantly surprised that food insecurity was more common among in-service members living on post. I was even more dismayed to read that a variety of factors constrained 14% of active-duty military experiencing food insecurity to seek public assistance to feed themselves and their families. As with so many health care and social services, (eg, mental health care), those wearing the uniform were concerned that participating in a food assistance program would damage their career or stigmatize them. Others did not seek help, perhaps because they believed they were not eligible, and in many cases were correct: they did not qualify for food banks or food stamps due to receiving other benefits. A variety of factors contribute to periods of food insecurity among military families, including remote or rural bases that lack access to grocery stores or jobs for partners or other family members, and low base military pay.⁵

Food insecurity is an even more serious concern among veterans who are frequently older and have more comorbidities, often leading to unemployment and homelessness. Feeding America, the nation’s largest organization of community food banks, estimates that 1 in 9 working-age veterans are food insecure.⁵ US Department of Veterans Affairs (VA) statistics indicate that veterans are 7% more likely to experience food insecurity than other sectors of the population.⁶ The Veterans Health Administration has recognized that food insecurity is directly related to medical problems already common among veterans, including diabetes, obesity, and depression. Women and minority veterans are the most at risk of food insecurity.⁷

Recognizing that many veterans are at risk of food insecurity, the US Department of Defense and VA have taken steps to try and reduce hunger among those who serve. In response to the shocking statistic that food insecurity was found in 27% of Iraq and Afghanistan veterans, the VA and Rockefeller Foundation are partnering on the Food as Medicine initiative to improve veteran nutrition as a means of improving nutrition-related health consequences of food insecurity.⁸

Like many federal practitioners, I was unaware of the food insecurity assistance available to active-duty service members or veterans, or how to help individuals access it. In addition to the resources outlined in the Table, there are many community-based options open to anyone, including veterans and service members. 

I have written columns on many difficult issues in my years as the Editor-in-Chief of Federal Practitioner, but personally this is one of the most distressing editorials I have ever published. That individuals dedicated to defending our rights and protecting our safety should be compelled to go hungry or not know if they have enough money at the end of the month to buy food is manifestly unjust. It is challenging when faced with such a large-scale injustice to think we cannot make a difference, but that resignation or abdication only magnifies this inequity. I have a friend who kept giving back even after they retired from federal service: they volunteered at a community garden and brought produce to the local food bank and helped distribute it. That may seem too much for those still working yet almost anyone can pick up a few items on their weekly shopping trip and donate them to a food drive. 

As we approach Veterans Day, let’s not just express our gratitude to our military and veterans in words but in deeds like feeding the hungry and urging elected representatives to fulfill their commitment to ensure that service members and veterans and their families do not experience food insecurity. Confucian wisdom written in a very distant time and vastly dissimilar context still rings true: there are direct and critical links between food and trust and between hunger and the military.¹

The requisites of government are that there be sufficiency of food, sufficiency of military equipment, and the confidence of the people in their ruler.

Analects by Confucius¹

From ancient festivals to modern holidays, autumn has long been associated with the gathering of the harvest. Friends and families come together around tables laden with delicious food to enjoy the pleasures of peace and plenty. During these celebrations, we must never forget that without the strength of the nation’s military and the service of its veterans, this freedom and abundance would not be possible. Our debt of gratitude to the current and former members of the armed services makes the fact that a substantial minority experiences food insecurity not only a human tragedy, but a travesty of the nation’s promise to support those who wear or have worn the uniform.

The National Defense Authorization Act for Fiscal Year 2020 charged the Secretary of Defense to investigate food insecurity among active-duty service members and their dependents.² The RAND Corporation conducted the assessment and, based on the results of its analysis, made recommendations to reduce hunger among armed forces members and their families.³

The RAND study found that 10% of active-duty military met US Department of Agriculture (USDA) criteria for very low food security; another 15% were classified as having low food security. The USDA defines food insecurity with hunger as “reports of multiple indications of disrupted eating patterns and reduced food intake.” USDA defines low food security as “reports of reduced quality, variety, or desirability of diet. Little or no indication of reduced food intake.”⁴

As someone who grew up on an Army base with the commissary a short trip from military housing, I was unpleasantly surprised that food insecurity was more common among in-service members living on post. I was even more dismayed to read that a variety of factors constrained 14% of active-duty military experiencing food insecurity to seek public assistance to feed themselves and their families. As with so many health care and social services, (eg, mental health care), those wearing the uniform were concerned that participating in a food assistance program would damage their career or stigmatize them. Others did not seek help, perhaps because they believed they were not eligible, and in many cases were correct: they did not qualify for food banks or food stamps due to receiving other benefits. A variety of factors contribute to periods of food insecurity among military families, including remote or rural bases that lack access to grocery stores or jobs for partners or other family members, and low base military pay.⁵

Food insecurity is an even more serious concern among veterans who are frequently older and have more comorbidities, often leading to unemployment and homelessness. Feeding America, the nation’s largest organization of community food banks, estimates that 1 in 9 working-age veterans are food insecure.⁵ US Department of Veterans Affairs (VA) statistics indicate that veterans are 7% more likely to experience food insecurity than other sectors of the population.⁶ The Veterans Health Administration has recognized that food insecurity is directly related to medical problems already common among veterans, including diabetes, obesity, and depression. Women and minority veterans are the most at risk of food insecurity.⁷

Recognizing that many veterans are at risk of food insecurity, the US Department of Defense and VA have taken steps to try and reduce hunger among those who serve. In response to the shocking statistic that food insecurity was found in 27% of Iraq and Afghanistan veterans, the VA and Rockefeller Foundation are partnering on the Food as Medicine initiative to improve veteran nutrition as a means of improving nutrition-related health consequences of food insecurity.⁸

Like many federal practitioners, I was unaware of the food insecurity assistance available to active-duty service members or veterans, or how to help individuals access it. In addition to the resources outlined in the Table, there are many community-based options open to anyone, including veterans and service members. 

I have written columns on many difficult issues in my years as the Editor-in-Chief of Federal Practitioner, but personally this is one of the most distressing editorials I have ever published. That individuals dedicated to defending our rights and protecting our safety should be compelled to go hungry or not know if they have enough money at the end of the month to buy food is manifestly unjust. It is challenging when faced with such a large-scale injustice to think we cannot make a difference, but that resignation or abdication only magnifies this inequity. I have a friend who kept giving back even after they retired from federal service: they volunteered at a community garden and brought produce to the local food bank and helped distribute it. That may seem too much for those still working yet almost anyone can pick up a few items on their weekly shopping trip and donate them to a food drive. 

As we approach Veterans Day, let’s not just express our gratitude to our military and veterans in words but in deeds like feeding the hungry and urging elected representatives to fulfill their commitment to ensure that service members and veterans and their families do not experience food insecurity. Confucian wisdom written in a very distant time and vastly dissimilar context still rings true: there are direct and critical links between food and trust and between hunger and the military.¹

The requisites of government are that there be sufficiency of food, sufficiency of military equipment, and the confidence of the people in their ruler.

Analects by Confucius¹

From ancient festivals to modern holidays, autumn has long been associated with the gathering of the harvest. Friends and families come together around tables laden with delicious food to enjoy the pleasures of peace and plenty. During these celebrations, we must never forget that without the strength of the nation’s military and the service of its veterans, this freedom and abundance would not be possible. Our debt of gratitude to the current and former members of the armed services makes the fact that a substantial minority experiences food insecurity not only a human tragedy, but a travesty of the nation’s promise to support those who wear or have worn the uniform.

The National Defense Authorization Act for Fiscal Year 2020 charged the Secretary of Defense to investigate food insecurity among active-duty service members and their dependents.² The RAND Corporation conducted the assessment and, based on the results of its analysis, made recommendations to reduce hunger among armed forces members and their families.³

The RAND study found that 10% of active-duty military met US Department of Agriculture (USDA) criteria for very low food security; another 15% were classified as having low food security. The USDA defines food insecurity with hunger as “reports of multiple indications of disrupted eating patterns and reduced food intake.” USDA defines low food security as “reports of reduced quality, variety, or desirability of diet. Little or no indication of reduced food intake.”⁴

As someone who grew up on an Army base with the commissary a short trip from military housing, I was unpleasantly surprised that food insecurity was more common among in-service members living on post. I was even more dismayed to read that a variety of factors constrained 14% of active-duty military experiencing food insecurity to seek public assistance to feed themselves and their families. As with so many health care and social services, (eg, mental health care), those wearing the uniform were concerned that participating in a food assistance program would damage their career or stigmatize them. Others did not seek help, perhaps because they believed they were not eligible, and in many cases were correct: they did not qualify for food banks or food stamps due to receiving other benefits. A variety of factors contribute to periods of food insecurity among military families, including remote or rural bases that lack access to grocery stores or jobs for partners or other family members, and low base military pay.⁵

Food insecurity is an even more serious concern among veterans who are frequently older and have more comorbidities, often leading to unemployment and homelessness. Feeding America, the nation’s largest organization of community food banks, estimates that 1 in 9 working-age veterans are food insecure.⁵ US Department of Veterans Affairs (VA) statistics indicate that veterans are 7% more likely to experience food insecurity than other sectors of the population.⁶ The Veterans Health Administration has recognized that food insecurity is directly related to medical problems already common among veterans, including diabetes, obesity, and depression. Women and minority veterans are the most at risk of food insecurity.⁷

Recognizing that many veterans are at risk of food insecurity, the US Department of Defense and VA have taken steps to try and reduce hunger among those who serve. In response to the shocking statistic that food insecurity was found in 27% of Iraq and Afghanistan veterans, the VA and Rockefeller Foundation are partnering on the Food as Medicine initiative to improve veteran nutrition as a means of improving nutrition-related health consequences of food insecurity.⁸

Like many federal practitioners, I was unaware of the food insecurity assistance available to active-duty service members or veterans, or how to help individuals access it. In addition to the resources outlined in the Table, there are many community-based options open to anyone, including veterans and service members. 

I have written columns on many difficult issues in my years as the Editor-in-Chief of Federal Practitioner, but personally this is one of the most distressing editorials I have ever published. That individuals dedicated to defending our rights and protecting our safety should be compelled to go hungry or not know if they have enough money at the end of the month to buy food is manifestly unjust. It is challenging when faced with such a large-scale injustice to think we cannot make a difference, but that resignation or abdication only magnifies this inequity. I have a friend who kept giving back even after they retired from federal service: they volunteered at a community garden and brought produce to the local food bank and helped distribute it. That may seem too much for those still working yet almost anyone can pick up a few items on their weekly shopping trip and donate them to a food drive. 

As we approach Veterans Day, let’s not just express our gratitude to our military and veterans in words but in deeds like feeding the hungry and urging elected representatives to fulfill their commitment to ensure that service members and veterans and their families do not experience food insecurity. Confucian wisdom written in a very distant time and vastly dissimilar context still rings true: there are direct and critical links between food and trust and between hunger and the military.¹

In 2020, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (CRC) increased the recommended colon polyp surveillance interval for 1 to 2 subcentimeter tubular adenomas from 5 to 10 years to 7 to 10 years.¹ This change was prompted by emerging research indicating that rates of CRC and advanced neoplasia among patients with a history of only 1 to 2 subcentimeter tubular adenomas are lower than initially estimated.^2,3 This extension provides an opportunity to increase endoscopy capacity and improve access to colonoscopies by retroactively applying the 2020 guidelines to surveillance interval recommendations made before their introduction. For example, based on the updated guidelines, patients previously recommended to undergo colon polyp surveillance colonoscopy 5 years after an index colonoscopy could extend their surveillance interval by 2 to 5 years. Increasing endoscopic capacity could address the growing demand for colonoscopies from new screening guidelines that reduced the age of initial CRC screening from 50 years to 45 years and the backlog of procedures due to COVID-19 restrictions.⁴

As part of a project to increase endoscopic capacity at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS), this study assessed the potential impact of retroactively applying the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity. These results may be informative for other VA and private-sector health care systems seeking to identify strategies to improve endoscopy capacity.

Methods

VAPHS is an integrated health care system in the Veterans Health Administration (VHA) serving 85,000 patients across 8 health care institutions in Pennsylvania, Ohio, and West Virginia. VAPHS manages colorectal screening recommendations for patients receiving medical care in the health care system regardless of whether their prior colonoscopy was performed at VAPHS or external facilities. The VA maintains a national CRC screening and surveillance electronic medical record reminder that prompts health care practitioners to order colon polyp surveillance based on interval recommendations from the index colonoscopy. This study reviewed all patients from the VAPHS panel with a reminder to undergo colonoscopy for screening for CRC or surveillance of colon polyps within 12 months from September 1, 2022.

Among patients with a reminder, 3 investigators reviewed index colonoscopy and pathology reports to identify CRC risk category, colonoscopy indication, procedural quality, and recommended repeat colonoscopy interval. Per the USMSTF guidelines, patients with incomplete colonoscopy or pathology records, high-risk indications (ie, personal history of inflammatory bowel disease, personal history of CRC, or family history of CRC), or inadequate bowel preparation (Boston Bowel Preparation Score < 6) were excluded. Additionally, patients who had CRC screening or surveillance discontinued due to age or comorbidities, had completed a subsequent follow-up colonoscopy, or were deceased at the time of review were excluded.

Retroactive Interval Reclassification

Among eligible patients, this study compared the repeat colonoscopy interval recommended by the prior endoscopist with those from the 2020 USMSTF guidelines. In cases where the interval was documented as a range of years, the lower end was considered the recommendation. Similarly, the lower end of the range from the 2020 USMSTF guidelines was used for the reclassified surveillance interval. Years extended per patient were quantified relative to September 1, 2023 (ie, 1 year after the review date). For example, if the index colonoscopy was completed on September 1, 2016, the initial surveillance recommendation was 5 years, and the reclassified recommendation was 7 years, the interval extension beyond September 1, 2023, was 0 years.

Furthermore, because index surveillance recommendations are not always guideline concordant, the years extended per patient were calculated by harmonizing the index endoscopist’s recommendations with the guidelines at the time of the index colonoscopy.⁵ For example, if the index colonoscopy was completed on September 1, 2018, and the endoscopist recommended a 5-year follow-up for a patient with average risk for CRC, adequate bowel preparation, and no colorectal polyps, that patient is eligible to extend their colonoscopy to September 1, 2028, based on guideline recommendations at the time of index endoscopy recommending that the next colonoscopy occur in 10 years. In this analysis the 2012 USMSTF guidelines were applied to all index colonoscopies completed in 2021 or earlier to allow time for adoption of the 2020 guidelines. 

This project fulfilled a facility mandate to increase capacity to conduct endoscopic procedures. Institutional review board approval was not required by VAPHS policy relating to clinical operations projects. Approval for publication of clinical operations activity was obtained from the VAPHS facility director.

Results

Within 1 year of the September 1, 2022, review date, 637 patients receiving care at VAPHS had clinical reminders for an upcoming colonoscopy. Of these, 54 (8.4%) were already up to date or were deceased at the time of review. Of the 583 eligible patients, 96% were male, the median age was 74 years, the median index colonoscopy year was 2016, and 178 (30.5%) had an average-risk CRC screening indication at the index colonoscopy (Table).

Of the 583 patients due for colonoscopy, 331 (56.7%) had both colonoscopy and pathology reports available. The majority of those with incomplete records had the index colonoscopy completed outside VAPHS. Among these patients, 222 (67.0%) had adequate bowel preparation. Of those with adequate bowel preparation, 43 were not eligible for interval extension because of high-risk conditions and 13 were not eligible because there was no index surveillance interval recommendation from the index endoscopist. Of the patients due for colonoscopy, 166 (28.4%) were potentially eligible for surveillance interval extension (Figure).  

Sixty-five (39.2%) of the 166 patients had 1 to 2 subcentimeter tubular adenomas on their index colonoscopy. Sixty-two patients were eligible for interval extension to 7 years, but this only resulted in ≥ 1 year of extension beyond the review date for 36 (6% of all 583 patients due for colonoscopy). The 36 patients were extended 63 years. By harmonizing the index endoscopists’ surveillance interval recommendation with the guideline at the time of the index colonoscopy, 29 additional patients could have their colonoscopy extended by ≥ 1 year. Harmonization extended colonoscopy intervals by 93 years. Retroactively applying the 2020 USMSTF polyp surveillance guidelines and harmonizing recommendations to guidelines extended the time of index colonoscopy by 153 years.

Discussion

With retroactive application of the 2020 USMSTF polyp surveillance guidelines, 6% of patients due for an upcoming colonoscopy could extend their follow-up by ≥ 1 year by extending the surveillance interval for 1 to 2 subcentimeter tubular adenomas to 7 years. An additional 5% of patients could extend their interval by harmonizing the index endoscopist’s interval recommendation with polyp surveillance guidelines at the time of the index colonoscopy. These findings are consistent with the results of 2 studies that demonstrated that about 14% of patients due for colonoscopy could have their interval extended.^6,7 The current study enhances those insights by separating the contribution of 2020 USMSTF polyp surveillance guidelines from the contribution of harmonizing surveillance intervals with guidelines for other polyp histologies. This study found that there is an opportunity to improve endoscopic capacity by harmonizing recommendations with guidelines. This complements a 2023 study showing that even when knowledgeable about guidelines, clinicians do not necessarily follow recommendations.⁸ While this and previous research have identified that 11% to 14% of patients are eligible for extension, these individuals would also have to be willing to have their polyp surveillance intervals extended for there to be a real-world impact on endoscopic capacity. A 2024 study found that only 19% to 37% of patients with 1 to 2 small tubular adenomas were willing to have polyps surveillance interval extension.⁹ This suggests the actual effect on capacity may be even lower than reported.

Limitations

The overall impact of the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity was blunted by the high prevalence of incomplete index colonoscopy records among the study population. Without data on bowel preparation quality or procedure indications, this study could not assess whether 43% of patients were eligible for surveillance interval extension. Most index colonoscopies with incomplete documentation were completed at community-care gastroenterology facilities. This high rate of incomplete documentation is likely generalizable to other VA health care systems—especially in the era of the Veterans Access, Choice, and Accountability Act of 2014, which increased veteran access to non-VA community care.¹⁰ Veterans due for colon polyp surveillance colonoscopies are more likely to have had their prior colonoscopy in community care compared with prior eras.¹¹ Furthermore, because the VHA is among the most established integrated health care systems offering primary and subspecialty care in the US, private sector health care systems may have even greater rates of care fragmentation for longitudinal CRC screening and colon polyp surveillance, as these systems have only begun to regionally integrate recently.^12,13

Another limitation is that nearly one-third of the individuals with documentation had inadequate bowel preparation for surveillance recommendations. This results in shorter surveillance follow-up colonoscopies and increases downstream demand for future colonoscopies. The low yield of extending colon polyp surveillance interval in this study emphasizes that improved efforts to obtain colonoscopy and pathology reports from community care, right-sizing the colon polyp surveillance intervals recommended by endoscopists, and improving quality of bowel preparation could have downstream health care system benefits in the future. These efforts could increase colonoscopy capacity at VA health care systems, thereby shortening colonoscopy wait times, decreasing fragmentation of care, and increasing the number of veterans who receive high-quality colonoscopies at VA health care systems.¹⁴

Conclusions

Eleven percent of patients in this study due for a colonoscopy could extend their follow-up by ≥ 1 year. About half of these extensions were directly due to the 2020 USMSTF polyp surveillance interval extension for 1 to 2 subcentimeter tubular adenomas. The rest resulted from harmonizing recommendations with guidelines at the time of the procedure. To determine whether retroactively applying polyp surveillance guidelines to follow-up interval recommendations will result in improved endoscopic capacity, health care system administrators should consider the degree of CRC screening care fragmentation in their patient population. Greater long-term gains in endoscopic capacity may be achieved by proactively supporting endoscopists in making guideline-concordant screening recommendations at the time of colonoscopy.

In 2020, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (CRC) increased the recommended colon polyp surveillance interval for 1 to 2 subcentimeter tubular adenomas from 5 to 10 years to 7 to 10 years.¹ This change was prompted by emerging research indicating that rates of CRC and advanced neoplasia among patients with a history of only 1 to 2 subcentimeter tubular adenomas are lower than initially estimated.^2,3 This extension provides an opportunity to increase endoscopy capacity and improve access to colonoscopies by retroactively applying the 2020 guidelines to surveillance interval recommendations made before their introduction. For example, based on the updated guidelines, patients previously recommended to undergo colon polyp surveillance colonoscopy 5 years after an index colonoscopy could extend their surveillance interval by 2 to 5 years. Increasing endoscopic capacity could address the growing demand for colonoscopies from new screening guidelines that reduced the age of initial CRC screening from 50 years to 45 years and the backlog of procedures due to COVID-19 restrictions.⁴

As part of a project to increase endoscopic capacity at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS), this study assessed the potential impact of retroactively applying the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity. These results may be informative for other VA and private-sector health care systems seeking to identify strategies to improve endoscopy capacity.

Methods

VAPHS is an integrated health care system in the Veterans Health Administration (VHA) serving 85,000 patients across 8 health care institutions in Pennsylvania, Ohio, and West Virginia. VAPHS manages colorectal screening recommendations for patients receiving medical care in the health care system regardless of whether their prior colonoscopy was performed at VAPHS or external facilities. The VA maintains a national CRC screening and surveillance electronic medical record reminder that prompts health care practitioners to order colon polyp surveillance based on interval recommendations from the index colonoscopy. This study reviewed all patients from the VAPHS panel with a reminder to undergo colonoscopy for screening for CRC or surveillance of colon polyps within 12 months from September 1, 2022.

Among patients with a reminder, 3 investigators reviewed index colonoscopy and pathology reports to identify CRC risk category, colonoscopy indication, procedural quality, and recommended repeat colonoscopy interval. Per the USMSTF guidelines, patients with incomplete colonoscopy or pathology records, high-risk indications (ie, personal history of inflammatory bowel disease, personal history of CRC, or family history of CRC), or inadequate bowel preparation (Boston Bowel Preparation Score < 6) were excluded. Additionally, patients who had CRC screening or surveillance discontinued due to age or comorbidities, had completed a subsequent follow-up colonoscopy, or were deceased at the time of review were excluded.

Retroactive Interval Reclassification

Among eligible patients, this study compared the repeat colonoscopy interval recommended by the prior endoscopist with those from the 2020 USMSTF guidelines. In cases where the interval was documented as a range of years, the lower end was considered the recommendation. Similarly, the lower end of the range from the 2020 USMSTF guidelines was used for the reclassified surveillance interval. Years extended per patient were quantified relative to September 1, 2023 (ie, 1 year after the review date). For example, if the index colonoscopy was completed on September 1, 2016, the initial surveillance recommendation was 5 years, and the reclassified recommendation was 7 years, the interval extension beyond September 1, 2023, was 0 years.

Furthermore, because index surveillance recommendations are not always guideline concordant, the years extended per patient were calculated by harmonizing the index endoscopist’s recommendations with the guidelines at the time of the index colonoscopy.⁵ For example, if the index colonoscopy was completed on September 1, 2018, and the endoscopist recommended a 5-year follow-up for a patient with average risk for CRC, adequate bowel preparation, and no colorectal polyps, that patient is eligible to extend their colonoscopy to September 1, 2028, based on guideline recommendations at the time of index endoscopy recommending that the next colonoscopy occur in 10 years. In this analysis the 2012 USMSTF guidelines were applied to all index colonoscopies completed in 2021 or earlier to allow time for adoption of the 2020 guidelines. 

This project fulfilled a facility mandate to increase capacity to conduct endoscopic procedures. Institutional review board approval was not required by VAPHS policy relating to clinical operations projects. Approval for publication of clinical operations activity was obtained from the VAPHS facility director.

Results

Within 1 year of the September 1, 2022, review date, 637 patients receiving care at VAPHS had clinical reminders for an upcoming colonoscopy. Of these, 54 (8.4%) were already up to date or were deceased at the time of review. Of the 583 eligible patients, 96% were male, the median age was 74 years, the median index colonoscopy year was 2016, and 178 (30.5%) had an average-risk CRC screening indication at the index colonoscopy (Table).

Of the 583 patients due for colonoscopy, 331 (56.7%) had both colonoscopy and pathology reports available. The majority of those with incomplete records had the index colonoscopy completed outside VAPHS. Among these patients, 222 (67.0%) had adequate bowel preparation. Of those with adequate bowel preparation, 43 were not eligible for interval extension because of high-risk conditions and 13 were not eligible because there was no index surveillance interval recommendation from the index endoscopist. Of the patients due for colonoscopy, 166 (28.4%) were potentially eligible for surveillance interval extension (Figure).  

Sixty-five (39.2%) of the 166 patients had 1 to 2 subcentimeter tubular adenomas on their index colonoscopy. Sixty-two patients were eligible for interval extension to 7 years, but this only resulted in ≥ 1 year of extension beyond the review date for 36 (6% of all 583 patients due for colonoscopy). The 36 patients were extended 63 years. By harmonizing the index endoscopists’ surveillance interval recommendation with the guideline at the time of the index colonoscopy, 29 additional patients could have their colonoscopy extended by ≥ 1 year. Harmonization extended colonoscopy intervals by 93 years. Retroactively applying the 2020 USMSTF polyp surveillance guidelines and harmonizing recommendations to guidelines extended the time of index colonoscopy by 153 years.

Discussion

With retroactive application of the 2020 USMSTF polyp surveillance guidelines, 6% of patients due for an upcoming colonoscopy could extend their follow-up by ≥ 1 year by extending the surveillance interval for 1 to 2 subcentimeter tubular adenomas to 7 years. An additional 5% of patients could extend their interval by harmonizing the index endoscopist’s interval recommendation with polyp surveillance guidelines at the time of the index colonoscopy. These findings are consistent with the results of 2 studies that demonstrated that about 14% of patients due for colonoscopy could have their interval extended.^6,7 The current study enhances those insights by separating the contribution of 2020 USMSTF polyp surveillance guidelines from the contribution of harmonizing surveillance intervals with guidelines for other polyp histologies. This study found that there is an opportunity to improve endoscopic capacity by harmonizing recommendations with guidelines. This complements a 2023 study showing that even when knowledgeable about guidelines, clinicians do not necessarily follow recommendations.⁸ While this and previous research have identified that 11% to 14% of patients are eligible for extension, these individuals would also have to be willing to have their polyp surveillance intervals extended for there to be a real-world impact on endoscopic capacity. A 2024 study found that only 19% to 37% of patients with 1 to 2 small tubular adenomas were willing to have polyps surveillance interval extension.⁹ This suggests the actual effect on capacity may be even lower than reported.

Limitations

The overall impact of the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity was blunted by the high prevalence of incomplete index colonoscopy records among the study population. Without data on bowel preparation quality or procedure indications, this study could not assess whether 43% of patients were eligible for surveillance interval extension. Most index colonoscopies with incomplete documentation were completed at community-care gastroenterology facilities. This high rate of incomplete documentation is likely generalizable to other VA health care systems—especially in the era of the Veterans Access, Choice, and Accountability Act of 2014, which increased veteran access to non-VA community care.¹⁰ Veterans due for colon polyp surveillance colonoscopies are more likely to have had their prior colonoscopy in community care compared with prior eras.¹¹ Furthermore, because the VHA is among the most established integrated health care systems offering primary and subspecialty care in the US, private sector health care systems may have even greater rates of care fragmentation for longitudinal CRC screening and colon polyp surveillance, as these systems have only begun to regionally integrate recently.^12,13

Another limitation is that nearly one-third of the individuals with documentation had inadequate bowel preparation for surveillance recommendations. This results in shorter surveillance follow-up colonoscopies and increases downstream demand for future colonoscopies. The low yield of extending colon polyp surveillance interval in this study emphasizes that improved efforts to obtain colonoscopy and pathology reports from community care, right-sizing the colon polyp surveillance intervals recommended by endoscopists, and improving quality of bowel preparation could have downstream health care system benefits in the future. These efforts could increase colonoscopy capacity at VA health care systems, thereby shortening colonoscopy wait times, decreasing fragmentation of care, and increasing the number of veterans who receive high-quality colonoscopies at VA health care systems.¹⁴

Conclusions

Eleven percent of patients in this study due for a colonoscopy could extend their follow-up by ≥ 1 year. About half of these extensions were directly due to the 2020 USMSTF polyp surveillance interval extension for 1 to 2 subcentimeter tubular adenomas. The rest resulted from harmonizing recommendations with guidelines at the time of the procedure. To determine whether retroactively applying polyp surveillance guidelines to follow-up interval recommendations will result in improved endoscopic capacity, health care system administrators should consider the degree of CRC screening care fragmentation in their patient population. Greater long-term gains in endoscopic capacity may be achieved by proactively supporting endoscopists in making guideline-concordant screening recommendations at the time of colonoscopy.

In 2020, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (CRC) increased the recommended colon polyp surveillance interval for 1 to 2 subcentimeter tubular adenomas from 5 to 10 years to 7 to 10 years.¹ This change was prompted by emerging research indicating that rates of CRC and advanced neoplasia among patients with a history of only 1 to 2 subcentimeter tubular adenomas are lower than initially estimated.^2,3 This extension provides an opportunity to increase endoscopy capacity and improve access to colonoscopies by retroactively applying the 2020 guidelines to surveillance interval recommendations made before their introduction. For example, based on the updated guidelines, patients previously recommended to undergo colon polyp surveillance colonoscopy 5 years after an index colonoscopy could extend their surveillance interval by 2 to 5 years. Increasing endoscopic capacity could address the growing demand for colonoscopies from new screening guidelines that reduced the age of initial CRC screening from 50 years to 45 years and the backlog of procedures due to COVID-19 restrictions.⁴

As part of a project to increase endoscopic capacity at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS), this study assessed the potential impact of retroactively applying the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity. These results may be informative for other VA and private-sector health care systems seeking to identify strategies to improve endoscopy capacity.

Methods

VAPHS is an integrated health care system in the Veterans Health Administration (VHA) serving 85,000 patients across 8 health care institutions in Pennsylvania, Ohio, and West Virginia. VAPHS manages colorectal screening recommendations for patients receiving medical care in the health care system regardless of whether their prior colonoscopy was performed at VAPHS or external facilities. The VA maintains a national CRC screening and surveillance electronic medical record reminder that prompts health care practitioners to order colon polyp surveillance based on interval recommendations from the index colonoscopy. This study reviewed all patients from the VAPHS panel with a reminder to undergo colonoscopy for screening for CRC or surveillance of colon polyps within 12 months from September 1, 2022.

Among patients with a reminder, 3 investigators reviewed index colonoscopy and pathology reports to identify CRC risk category, colonoscopy indication, procedural quality, and recommended repeat colonoscopy interval. Per the USMSTF guidelines, patients with incomplete colonoscopy or pathology records, high-risk indications (ie, personal history of inflammatory bowel disease, personal history of CRC, or family history of CRC), or inadequate bowel preparation (Boston Bowel Preparation Score < 6) were excluded. Additionally, patients who had CRC screening or surveillance discontinued due to age or comorbidities, had completed a subsequent follow-up colonoscopy, or were deceased at the time of review were excluded.

Retroactive Interval Reclassification

Among eligible patients, this study compared the repeat colonoscopy interval recommended by the prior endoscopist with those from the 2020 USMSTF guidelines. In cases where the interval was documented as a range of years, the lower end was considered the recommendation. Similarly, the lower end of the range from the 2020 USMSTF guidelines was used for the reclassified surveillance interval. Years extended per patient were quantified relative to September 1, 2023 (ie, 1 year after the review date). For example, if the index colonoscopy was completed on September 1, 2016, the initial surveillance recommendation was 5 years, and the reclassified recommendation was 7 years, the interval extension beyond September 1, 2023, was 0 years.

Furthermore, because index surveillance recommendations are not always guideline concordant, the years extended per patient were calculated by harmonizing the index endoscopist’s recommendations with the guidelines at the time of the index colonoscopy.⁵ For example, if the index colonoscopy was completed on September 1, 2018, and the endoscopist recommended a 5-year follow-up for a patient with average risk for CRC, adequate bowel preparation, and no colorectal polyps, that patient is eligible to extend their colonoscopy to September 1, 2028, based on guideline recommendations at the time of index endoscopy recommending that the next colonoscopy occur in 10 years. In this analysis the 2012 USMSTF guidelines were applied to all index colonoscopies completed in 2021 or earlier to allow time for adoption of the 2020 guidelines. 

This project fulfilled a facility mandate to increase capacity to conduct endoscopic procedures. Institutional review board approval was not required by VAPHS policy relating to clinical operations projects. Approval for publication of clinical operations activity was obtained from the VAPHS facility director.

Results

Within 1 year of the September 1, 2022, review date, 637 patients receiving care at VAPHS had clinical reminders for an upcoming colonoscopy. Of these, 54 (8.4%) were already up to date or were deceased at the time of review. Of the 583 eligible patients, 96% were male, the median age was 74 years, the median index colonoscopy year was 2016, and 178 (30.5%) had an average-risk CRC screening indication at the index colonoscopy (Table).

Of the 583 patients due for colonoscopy, 331 (56.7%) had both colonoscopy and pathology reports available. The majority of those with incomplete records had the index colonoscopy completed outside VAPHS. Among these patients, 222 (67.0%) had adequate bowel preparation. Of those with adequate bowel preparation, 43 were not eligible for interval extension because of high-risk conditions and 13 were not eligible because there was no index surveillance interval recommendation from the index endoscopist. Of the patients due for colonoscopy, 166 (28.4%) were potentially eligible for surveillance interval extension (Figure).  

Sixty-five (39.2%) of the 166 patients had 1 to 2 subcentimeter tubular adenomas on their index colonoscopy. Sixty-two patients were eligible for interval extension to 7 years, but this only resulted in ≥ 1 year of extension beyond the review date for 36 (6% of all 583 patients due for colonoscopy). The 36 patients were extended 63 years. By harmonizing the index endoscopists’ surveillance interval recommendation with the guideline at the time of the index colonoscopy, 29 additional patients could have their colonoscopy extended by ≥ 1 year. Harmonization extended colonoscopy intervals by 93 years. Retroactively applying the 2020 USMSTF polyp surveillance guidelines and harmonizing recommendations to guidelines extended the time of index colonoscopy by 153 years.

Discussion

With retroactive application of the 2020 USMSTF polyp surveillance guidelines, 6% of patients due for an upcoming colonoscopy could extend their follow-up by ≥ 1 year by extending the surveillance interval for 1 to 2 subcentimeter tubular adenomas to 7 years. An additional 5% of patients could extend their interval by harmonizing the index endoscopist’s interval recommendation with polyp surveillance guidelines at the time of the index colonoscopy. These findings are consistent with the results of 2 studies that demonstrated that about 14% of patients due for colonoscopy could have their interval extended.^6,7 The current study enhances those insights by separating the contribution of 2020 USMSTF polyp surveillance guidelines from the contribution of harmonizing surveillance intervals with guidelines for other polyp histologies. This study found that there is an opportunity to improve endoscopic capacity by harmonizing recommendations with guidelines. This complements a 2023 study showing that even when knowledgeable about guidelines, clinicians do not necessarily follow recommendations.⁸ While this and previous research have identified that 11% to 14% of patients are eligible for extension, these individuals would also have to be willing to have their polyp surveillance intervals extended for there to be a real-world impact on endoscopic capacity. A 2024 study found that only 19% to 37% of patients with 1 to 2 small tubular adenomas were willing to have polyps surveillance interval extension.⁹ This suggests the actual effect on capacity may be even lower than reported.

Limitations

The overall impact of the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity was blunted by the high prevalence of incomplete index colonoscopy records among the study population. Without data on bowel preparation quality or procedure indications, this study could not assess whether 43% of patients were eligible for surveillance interval extension. Most index colonoscopies with incomplete documentation were completed at community-care gastroenterology facilities. This high rate of incomplete documentation is likely generalizable to other VA health care systems—especially in the era of the Veterans Access, Choice, and Accountability Act of 2014, which increased veteran access to non-VA community care.¹⁰ Veterans due for colon polyp surveillance colonoscopies are more likely to have had their prior colonoscopy in community care compared with prior eras.¹¹ Furthermore, because the VHA is among the most established integrated health care systems offering primary and subspecialty care in the US, private sector health care systems may have even greater rates of care fragmentation for longitudinal CRC screening and colon polyp surveillance, as these systems have only begun to regionally integrate recently.^12,13

Another limitation is that nearly one-third of the individuals with documentation had inadequate bowel preparation for surveillance recommendations. This results in shorter surveillance follow-up colonoscopies and increases downstream demand for future colonoscopies. The low yield of extending colon polyp surveillance interval in this study emphasizes that improved efforts to obtain colonoscopy and pathology reports from community care, right-sizing the colon polyp surveillance intervals recommended by endoscopists, and improving quality of bowel preparation could have downstream health care system benefits in the future. These efforts could increase colonoscopy capacity at VA health care systems, thereby shortening colonoscopy wait times, decreasing fragmentation of care, and increasing the number of veterans who receive high-quality colonoscopies at VA health care systems.¹⁴

Conclusions

Eleven percent of patients in this study due for a colonoscopy could extend their follow-up by ≥ 1 year. About half of these extensions were directly due to the 2020 USMSTF polyp surveillance interval extension for 1 to 2 subcentimeter tubular adenomas. The rest resulted from harmonizing recommendations with guidelines at the time of the procedure. To determine whether retroactively applying polyp surveillance guidelines to follow-up interval recommendations will result in improved endoscopic capacity, health care system administrators should consider the degree of CRC screening care fragmentation in their patient population. Greater long-term gains in endoscopic capacity may be achieved by proactively supporting endoscopists in making guideline-concordant screening recommendations at the time of colonoscopy.

Tracheal deviation mostly occurs from mechanical compression of the trachea, and can be caused by a variety of clinical conditions, including trauma,¹ pharyngeal abscess,² neck hematoma,³ thyroid enlargement,⁴ and kyphoscoliosis.⁵ These conditions often result in lateral tracheal deviation, which can be associated with tracheal compression and reduction in tracheal caliber.

Anterior-posterior (A-P) tracheal deviation has rarely been reported. Kyphoscoliosis, scarring after a tracheostomy, or innominate vein compression are probable causes of A-P tracheal deviation and can be associated with tracheal narrowing and vascular fistula formation. This report describes a case of difficult endotracheal tube (ETT) advancement secondary to unexpected acute posterior tracheal deviation encountered during cardiopulmonary resuscitation (CPR). A waiver of patient consent was obtained from the Human Research Protection Program at the US Department of Veterans Affairs (VA) Puget Sound Health Care System.

Case Presentation

A 50-year-old male with a history of chronic cerebral venous sinus thrombosis and taking enoxaparin, presented to the emergency department for recurrent headaches. He experienced sudden cardiac arrest, and CPR in the form of chest compression and bag mask ventilation was immediately initiated. With the patient's head in an extended position and using a video laryngoscope, a Cormack–Lehane grade 1 view of the glottic opening was obtained and the trachea was intubated with an 8 mm (internal diameter) polyvinyl chloride ETT. Tracheal intubation was confirmed by utilizing continuous EtCO₂ monitoring. The ETT was secured at 22 cm measured at the teeth.

After about 40 minutes of CPR, spontaneous circulation restarted and a portable A-P chest X-ray with the head in a neutral position indicated the ETT tip was at the level of the first rib (Figure 1). This finding, along with a persistent air leak, prompted blind advancement of the ETT to 26 cm at the teeth, but resistance to advancement was noted. A subsequent chest computed tomography (CT) with the head in a neutral position revealed the ETT remained inappropriately positioned with the tip measured 8.2 cm above the carina (Figure 2A). Concurrently, a sagittal CT view demonstrated significant posterior deviation of the mid and lower trachea. This deviation was determined to be the most likely cause of the difficulty encountered in advancing the ETT. No masses or lesions contributing to the acute tracheal angulation could be identified. Comparing CT imaging from 2 months prior, the trachea was of normal caliber and ordinarily aligned with the vertebral column (Figure 2B).

With the patient in Fowler position with the head midline, a flexible fiber-optic bronchoscopy was performed. Acute, almost 90-degree tracheal angulation was encountered and navigated by retroflexion of the flexible bronchoscope. Once the posterior tracheal wall was encountered, retroflexion was relaxed and the carina was visualized. The bronchoscope tip was placed near the carina, and the ETT was advanced over the fiber-optic bronchoscope to terminate 3 cm above the carina. A subsequent chest X-ray confirmed appropriate ETT position (Figure 3).

Discussion

Tracheal deviation in the A-P dimension resulting in difficult tracheal intubation has rarely been reported. Previous reports have described anatomical lesions contributing to similar tracheal deviation, such as retro-tracheal thyroid tissue, pronounced cervical lordosis, and severe kyphoscoliosis with destructive cervical fusion.^5-8 In a study of the anatomical correlation of double lumen tube placement while using positron emission tomography CT, Cameron et al evaluated the size and angulation of the glottis and proximal trachea using calibrated CT measurements and an online digital protractor and note nearly perfect alignment of the pharynx and glottis.⁹ However, the trachea turned posteriorly relative to the glottis, resulting in an overall posterior angle of the proximal trachea compared to the glottis of 30.4 to 50.1 degrees, with no sex differences. The need to maneuver similar proximal tracheal angulation during endotracheal intubation has been reported as a cause of difficult intubation.¹⁰

In this case, the posterior angulation was not encountered in the proximal trachea but rather in the more distal trachea. The extreme A-P tracheal deviation was not associated with any identifiable masses or lesions. A CT performed 2 months prior demonstrated normal tracheal anatomy, and there was no interval history of neck trauma or tracheal obstruction suggestive of a likely cause for this deviation. This change in the patient’s tracheal anatomy was only discovered after CPR had been performed and as part of the workup for cardiac arrest. Iatrogenic injuries are known to occur during CPR. Common CPR-related airway injuries include tracheal mucosal injury from traumatic intubation and bony injuries to the chest wall from compressions.¹¹ Laryngeal cartilage damage from intubation may also occur, but tracheal displacement following CPR has not been previously reported.¹¹

This case of tracheal deviation is unlikely to be related to patient positioning, as the A-P deviation persisted in 3 separate head and neck alignments. First, during indirect laryngoscopy, performed in a standard sniffing position. Second, during the CT, performed in the supine position, with no head support. The acute A-P deviation seen in Figure 2 was clearly noted in this position. Lastly, flexible fiber-optic bronchoscopy was performed in a semiupright position with the head supported on a pillow. A-P deviation was encountered and navigated in this position during flexible fiber-optic guided ETT repositioning. 

Using magnetic resonance imaging, alterations in the alignment of pharyngeal and tracheal axes have been described with changes in neck positioning; however, tracheal deviation has not been described with changes in head and neck alignment.¹² Although the clinical presentation in this case was consistent with prior reports, we were unable to identify any previously reported anatomic cause for the tracheal deviation.^5,6,8 Initial glottic visualization with a video laryngoscope was unremarkable, but resistance to sufficient ETT advancement past the vocal cords and a persistent air leak due to cuff herniation through the glottic opening was noticeable. The ETT was maneuvered to an appropriate position in the trachea using a flexible fiber-optic bronchoscope. The acute angulation of the trachea that was appreciated on bronchoscopy did not result in kinking of the ETT both initially and after in-situ thermosoftening of the polyvinyl chloride tube.¹³ Previously reported instances of A-P tracheal deviation have outlined the necessity of using alternative techniques to establish a patent airway, including the use of a laryngeal mask airway and a cuffless ETT with saline-soaked gauze packing.^5,8 In 1 reported case, awake fiber-optic intubation was performed when difficult tracheal intubation was anticipated due to known A-P tracheal deviation.⁶

Failure of ETT advancement can be due to obstruction from the arytenoids and at the level of the vocal cords.¹⁴ When the ETT has been visualized to have traversed the vocal cords, tracheal A-P deviation should be considered as a cause of difficult ETT advancement. If an adequate endotracheal airway cannot be established, prompt consideration should be given to placement of a supraglottic airway. Early fiber-optic bronchoscopy should be used to establish the diagnosis and assist with proper ETT positioning.

Conclusions

This case illustrates the rare occurrence of A-P tracheal deviation leading to difficult intubation during CPR. The findings underscore the importance of considering A-P deviation as a potential cause of airway complications in emergency settings, especially in patients with previously normal tracheal anatomy. The successful use of flexible fiber-optic bronchoscopy in this case provides a valuable technique for addressing acute tracheal angulation. This report contributes to the limited literature on A-P tracheal deviation and serves as a reminder for clinicians to maintain a high index of suspicion for unusual airway challenges during critical interventions.

Tracheal deviation mostly occurs from mechanical compression of the trachea, and can be caused by a variety of clinical conditions, including trauma,¹ pharyngeal abscess,² neck hematoma,³ thyroid enlargement,⁴ and kyphoscoliosis.⁵ These conditions often result in lateral tracheal deviation, which can be associated with tracheal compression and reduction in tracheal caliber.

Anterior-posterior (A-P) tracheal deviation has rarely been reported. Kyphoscoliosis, scarring after a tracheostomy, or innominate vein compression are probable causes of A-P tracheal deviation and can be associated with tracheal narrowing and vascular fistula formation. This report describes a case of difficult endotracheal tube (ETT) advancement secondary to unexpected acute posterior tracheal deviation encountered during cardiopulmonary resuscitation (CPR). A waiver of patient consent was obtained from the Human Research Protection Program at the US Department of Veterans Affairs (VA) Puget Sound Health Care System.

Case Presentation

A 50-year-old male with a history of chronic cerebral venous sinus thrombosis and taking enoxaparin, presented to the emergency department for recurrent headaches. He experienced sudden cardiac arrest, and CPR in the form of chest compression and bag mask ventilation was immediately initiated. With the patient's head in an extended position and using a video laryngoscope, a Cormack–Lehane grade 1 view of the glottic opening was obtained and the trachea was intubated with an 8 mm (internal diameter) polyvinyl chloride ETT. Tracheal intubation was confirmed by utilizing continuous EtCO₂ monitoring. The ETT was secured at 22 cm measured at the teeth.

After about 40 minutes of CPR, spontaneous circulation restarted and a portable A-P chest X-ray with the head in a neutral position indicated the ETT tip was at the level of the first rib (Figure 1). This finding, along with a persistent air leak, prompted blind advancement of the ETT to 26 cm at the teeth, but resistance to advancement was noted. A subsequent chest computed tomography (CT) with the head in a neutral position revealed the ETT remained inappropriately positioned with the tip measured 8.2 cm above the carina (Figure 2A). Concurrently, a sagittal CT view demonstrated significant posterior deviation of the mid and lower trachea. This deviation was determined to be the most likely cause of the difficulty encountered in advancing the ETT. No masses or lesions contributing to the acute tracheal angulation could be identified. Comparing CT imaging from 2 months prior, the trachea was of normal caliber and ordinarily aligned with the vertebral column (Figure 2B).

With the patient in Fowler position with the head midline, a flexible fiber-optic bronchoscopy was performed. Acute, almost 90-degree tracheal angulation was encountered and navigated by retroflexion of the flexible bronchoscope. Once the posterior tracheal wall was encountered, retroflexion was relaxed and the carina was visualized. The bronchoscope tip was placed near the carina, and the ETT was advanced over the fiber-optic bronchoscope to terminate 3 cm above the carina. A subsequent chest X-ray confirmed appropriate ETT position (Figure 3).

Discussion

Tracheal deviation in the A-P dimension resulting in difficult tracheal intubation has rarely been reported. Previous reports have described anatomical lesions contributing to similar tracheal deviation, such as retro-tracheal thyroid tissue, pronounced cervical lordosis, and severe kyphoscoliosis with destructive cervical fusion.^5-8 In a study of the anatomical correlation of double lumen tube placement while using positron emission tomography CT, Cameron et al evaluated the size and angulation of the glottis and proximal trachea using calibrated CT measurements and an online digital protractor and note nearly perfect alignment of the pharynx and glottis.⁹ However, the trachea turned posteriorly relative to the glottis, resulting in an overall posterior angle of the proximal trachea compared to the glottis of 30.4 to 50.1 degrees, with no sex differences. The need to maneuver similar proximal tracheal angulation during endotracheal intubation has been reported as a cause of difficult intubation.¹⁰

In this case, the posterior angulation was not encountered in the proximal trachea but rather in the more distal trachea. The extreme A-P tracheal deviation was not associated with any identifiable masses or lesions. A CT performed 2 months prior demonstrated normal tracheal anatomy, and there was no interval history of neck trauma or tracheal obstruction suggestive of a likely cause for this deviation. This change in the patient’s tracheal anatomy was only discovered after CPR had been performed and as part of the workup for cardiac arrest. Iatrogenic injuries are known to occur during CPR. Common CPR-related airway injuries include tracheal mucosal injury from traumatic intubation and bony injuries to the chest wall from compressions.¹¹ Laryngeal cartilage damage from intubation may also occur, but tracheal displacement following CPR has not been previously reported.¹¹

This case of tracheal deviation is unlikely to be related to patient positioning, as the A-P deviation persisted in 3 separate head and neck alignments. First, during indirect laryngoscopy, performed in a standard sniffing position. Second, during the CT, performed in the supine position, with no head support. The acute A-P deviation seen in Figure 2 was clearly noted in this position. Lastly, flexible fiber-optic bronchoscopy was performed in a semiupright position with the head supported on a pillow. A-P deviation was encountered and navigated in this position during flexible fiber-optic guided ETT repositioning. 

Using magnetic resonance imaging, alterations in the alignment of pharyngeal and tracheal axes have been described with changes in neck positioning; however, tracheal deviation has not been described with changes in head and neck alignment.¹² Although the clinical presentation in this case was consistent with prior reports, we were unable to identify any previously reported anatomic cause for the tracheal deviation.^5,6,8 Initial glottic visualization with a video laryngoscope was unremarkable, but resistance to sufficient ETT advancement past the vocal cords and a persistent air leak due to cuff herniation through the glottic opening was noticeable. The ETT was maneuvered to an appropriate position in the trachea using a flexible fiber-optic bronchoscope. The acute angulation of the trachea that was appreciated on bronchoscopy did not result in kinking of the ETT both initially and after in-situ thermosoftening of the polyvinyl chloride tube.¹³ Previously reported instances of A-P tracheal deviation have outlined the necessity of using alternative techniques to establish a patent airway, including the use of a laryngeal mask airway and a cuffless ETT with saline-soaked gauze packing.^5,8 In 1 reported case, awake fiber-optic intubation was performed when difficult tracheal intubation was anticipated due to known A-P tracheal deviation.⁶

Failure of ETT advancement can be due to obstruction from the arytenoids and at the level of the vocal cords.¹⁴ When the ETT has been visualized to have traversed the vocal cords, tracheal A-P deviation should be considered as a cause of difficult ETT advancement. If an adequate endotracheal airway cannot be established, prompt consideration should be given to placement of a supraglottic airway. Early fiber-optic bronchoscopy should be used to establish the diagnosis and assist with proper ETT positioning.

Conclusions

This case illustrates the rare occurrence of A-P tracheal deviation leading to difficult intubation during CPR. The findings underscore the importance of considering A-P deviation as a potential cause of airway complications in emergency settings, especially in patients with previously normal tracheal anatomy. The successful use of flexible fiber-optic bronchoscopy in this case provides a valuable technique for addressing acute tracheal angulation. This report contributes to the limited literature on A-P tracheal deviation and serves as a reminder for clinicians to maintain a high index of suspicion for unusual airway challenges during critical interventions.

Tracheal deviation mostly occurs from mechanical compression of the trachea, and can be caused by a variety of clinical conditions, including trauma,¹ pharyngeal abscess,² neck hematoma,³ thyroid enlargement,⁴ and kyphoscoliosis.⁵ These conditions often result in lateral tracheal deviation, which can be associated with tracheal compression and reduction in tracheal caliber.

Anterior-posterior (A-P) tracheal deviation has rarely been reported. Kyphoscoliosis, scarring after a tracheostomy, or innominate vein compression are probable causes of A-P tracheal deviation and can be associated with tracheal narrowing and vascular fistula formation. This report describes a case of difficult endotracheal tube (ETT) advancement secondary to unexpected acute posterior tracheal deviation encountered during cardiopulmonary resuscitation (CPR). A waiver of patient consent was obtained from the Human Research Protection Program at the US Department of Veterans Affairs (VA) Puget Sound Health Care System.

Case Presentation

A 50-year-old male with a history of chronic cerebral venous sinus thrombosis and taking enoxaparin, presented to the emergency department for recurrent headaches. He experienced sudden cardiac arrest, and CPR in the form of chest compression and bag mask ventilation was immediately initiated. With the patient's head in an extended position and using a video laryngoscope, a Cormack–Lehane grade 1 view of the glottic opening was obtained and the trachea was intubated with an 8 mm (internal diameter) polyvinyl chloride ETT. Tracheal intubation was confirmed by utilizing continuous EtCO₂ monitoring. The ETT was secured at 22 cm measured at the teeth.

After about 40 minutes of CPR, spontaneous circulation restarted and a portable A-P chest X-ray with the head in a neutral position indicated the ETT tip was at the level of the first rib (Figure 1). This finding, along with a persistent air leak, prompted blind advancement of the ETT to 26 cm at the teeth, but resistance to advancement was noted. A subsequent chest computed tomography (CT) with the head in a neutral position revealed the ETT remained inappropriately positioned with the tip measured 8.2 cm above the carina (Figure 2A). Concurrently, a sagittal CT view demonstrated significant posterior deviation of the mid and lower trachea. This deviation was determined to be the most likely cause of the difficulty encountered in advancing the ETT. No masses or lesions contributing to the acute tracheal angulation could be identified. Comparing CT imaging from 2 months prior, the trachea was of normal caliber and ordinarily aligned with the vertebral column (Figure 2B).

With the patient in Fowler position with the head midline, a flexible fiber-optic bronchoscopy was performed. Acute, almost 90-degree tracheal angulation was encountered and navigated by retroflexion of the flexible bronchoscope. Once the posterior tracheal wall was encountered, retroflexion was relaxed and the carina was visualized. The bronchoscope tip was placed near the carina, and the ETT was advanced over the fiber-optic bronchoscope to terminate 3 cm above the carina. A subsequent chest X-ray confirmed appropriate ETT position (Figure 3).

Discussion

Tracheal deviation in the A-P dimension resulting in difficult tracheal intubation has rarely been reported. Previous reports have described anatomical lesions contributing to similar tracheal deviation, such as retro-tracheal thyroid tissue, pronounced cervical lordosis, and severe kyphoscoliosis with destructive cervical fusion.^5-8 In a study of the anatomical correlation of double lumen tube placement while using positron emission tomography CT, Cameron et al evaluated the size and angulation of the glottis and proximal trachea using calibrated CT measurements and an online digital protractor and note nearly perfect alignment of the pharynx and glottis.⁹ However, the trachea turned posteriorly relative to the glottis, resulting in an overall posterior angle of the proximal trachea compared to the glottis of 30.4 to 50.1 degrees, with no sex differences. The need to maneuver similar proximal tracheal angulation during endotracheal intubation has been reported as a cause of difficult intubation.¹⁰

In this case, the posterior angulation was not encountered in the proximal trachea but rather in the more distal trachea. The extreme A-P tracheal deviation was not associated with any identifiable masses or lesions. A CT performed 2 months prior demonstrated normal tracheal anatomy, and there was no interval history of neck trauma or tracheal obstruction suggestive of a likely cause for this deviation. This change in the patient’s tracheal anatomy was only discovered after CPR had been performed and as part of the workup for cardiac arrest. Iatrogenic injuries are known to occur during CPR. Common CPR-related airway injuries include tracheal mucosal injury from traumatic intubation and bony injuries to the chest wall from compressions.¹¹ Laryngeal cartilage damage from intubation may also occur, but tracheal displacement following CPR has not been previously reported.¹¹

This case of tracheal deviation is unlikely to be related to patient positioning, as the A-P deviation persisted in 3 separate head and neck alignments. First, during indirect laryngoscopy, performed in a standard sniffing position. Second, during the CT, performed in the supine position, with no head support. The acute A-P deviation seen in Figure 2 was clearly noted in this position. Lastly, flexible fiber-optic bronchoscopy was performed in a semiupright position with the head supported on a pillow. A-P deviation was encountered and navigated in this position during flexible fiber-optic guided ETT repositioning. 

Using magnetic resonance imaging, alterations in the alignment of pharyngeal and tracheal axes have been described with changes in neck positioning; however, tracheal deviation has not been described with changes in head and neck alignment.¹² Although the clinical presentation in this case was consistent with prior reports, we were unable to identify any previously reported anatomic cause for the tracheal deviation.^5,6,8 Initial glottic visualization with a video laryngoscope was unremarkable, but resistance to sufficient ETT advancement past the vocal cords and a persistent air leak due to cuff herniation through the glottic opening was noticeable. The ETT was maneuvered to an appropriate position in the trachea using a flexible fiber-optic bronchoscope. The acute angulation of the trachea that was appreciated on bronchoscopy did not result in kinking of the ETT both initially and after in-situ thermosoftening of the polyvinyl chloride tube.¹³ Previously reported instances of A-P tracheal deviation have outlined the necessity of using alternative techniques to establish a patent airway, including the use of a laryngeal mask airway and a cuffless ETT with saline-soaked gauze packing.^5,8 In 1 reported case, awake fiber-optic intubation was performed when difficult tracheal intubation was anticipated due to known A-P tracheal deviation.⁶

Failure of ETT advancement can be due to obstruction from the arytenoids and at the level of the vocal cords.¹⁴ When the ETT has been visualized to have traversed the vocal cords, tracheal A-P deviation should be considered as a cause of difficult ETT advancement. If an adequate endotracheal airway cannot be established, prompt consideration should be given to placement of a supraglottic airway. Early fiber-optic bronchoscopy should be used to establish the diagnosis and assist with proper ETT positioning.

Conclusions

This case illustrates the rare occurrence of A-P tracheal deviation leading to difficult intubation during CPR. The findings underscore the importance of considering A-P deviation as a potential cause of airway complications in emergency settings, especially in patients with previously normal tracheal anatomy. The successful use of flexible fiber-optic bronchoscopy in this case provides a valuable technique for addressing acute tracheal angulation. This report contributes to the limited literature on A-P tracheal deviation and serves as a reminder for clinicians to maintain a high index of suspicion for unusual airway challenges during critical interventions.

To the Editor:

Necrobiotic xanthogranuloma (NXG) is classified as a cutaneous non–Langerhans cell histiocytosis, often seen with monoclonal gammopathy of undetermined significance or multiple myeloma.¹ Clinically, it appears as a red or yellow plaque with occasional ulceration and telangiectasias, most commonly seen periorbitally and on the trunk. On pathology, NXG appears as necrobiosis, giant cells, and various inflammatory cells extending into the subcutaneous tissue.² In this article, we describe a rare presentation of NXG in location and skin type.

A 52-year-old woman with a history of systemic lupus erythematosus (SLE) presented with alopecia and a tender lesion on the scalp of 5 years’ duration (Figure 1). The patient had no history of a similar lesion, and no other lesions were present. A biopsy performed at an outside clinic a few weeks to months prior to the initial presentation to our clinic showed NXG (Figure 2). Evaluation at our clinic revealed a 4x4-cm orange-brown annular plaque on the left parietal scalp. Serum and urine protein electrophoresis studies were negative. The patient reported she was up to date with recommended screenings such as mammography and colonoscopy. 

We started the patient on topical triamcinolone and topical ruxolitinib and administered intralesional triamcinolone. She was already taking hydroxychloroquine and leflunomide for SLE. Three weeks later, she returned with improved symptoms and appearance (Figure 1). She remained on intralesional triamcinolone and ruxolitinib and continues to experience improvement.

Necrobiotic xanthogranuloma is rare and typically is associated with monoclonal gammopathy.² In one study, 83 of 100 of patients with NXG presented with or were found to have a monoclonal gammopathy.² In another study, paraproteinemia was detected in 82.1% of patients.³ The majority of case reports and systematic reviews detail periorbital or thoracic lesions.⁴ The location on the scalp and lack of association with paraproteinemia make this a rare presentation of NXG. Studies may be warranted to explore any association of SLE with NXG if more cases present.

In a multicenter cross-sectional study and systematic review of 235 patients with NXG, 87% were White, 12% were Asian, and only 1% were Black or African American.³ The limited representation of skin of color raises concern for the possibility of missed diagnoses and delays in care. 

Treatment of NXG often is multimodal with use of intravenous immunoglobulin, oral steroids, chlorambucil, melphalan, and other alkylating agents, and response is variable.^3-6 Recent studies show treatment effectiveness with Janus kinase inhibitors in granulomatous dermatitides.^7-9 As our patient was not responding to prior treatments, we decided to try ruxolitinib, and she has continued to improve with it.^10,11 Interestingly, the patient experienced continued improvement with intralesional triamcinolone, which is not often reported in the literature.^2-6 Overall, NXG is an extremely rare condition that requires special care in workup to rule out paraproteinemia and a thoughtful approach to treatment modalities.

To the Editor:

Necrobiotic xanthogranuloma (NXG) is classified as a cutaneous non–Langerhans cell histiocytosis, often seen with monoclonal gammopathy of undetermined significance or multiple myeloma.¹ Clinically, it appears as a red or yellow plaque with occasional ulceration and telangiectasias, most commonly seen periorbitally and on the trunk. On pathology, NXG appears as necrobiosis, giant cells, and various inflammatory cells extending into the subcutaneous tissue.² In this article, we describe a rare presentation of NXG in location and skin type.

A 52-year-old woman with a history of systemic lupus erythematosus (SLE) presented with alopecia and a tender lesion on the scalp of 5 years’ duration (Figure 1). The patient had no history of a similar lesion, and no other lesions were present. A biopsy performed at an outside clinic a few weeks to months prior to the initial presentation to our clinic showed NXG (Figure 2). Evaluation at our clinic revealed a 4x4-cm orange-brown annular plaque on the left parietal scalp. Serum and urine protein electrophoresis studies were negative. The patient reported she was up to date with recommended screenings such as mammography and colonoscopy. 

We started the patient on topical triamcinolone and topical ruxolitinib and administered intralesional triamcinolone. She was already taking hydroxychloroquine and leflunomide for SLE. Three weeks later, she returned with improved symptoms and appearance (Figure 1). She remained on intralesional triamcinolone and ruxolitinib and continues to experience improvement.

Necrobiotic xanthogranuloma is rare and typically is associated with monoclonal gammopathy.² In one study, 83 of 100 of patients with NXG presented with or were found to have a monoclonal gammopathy.² In another study, paraproteinemia was detected in 82.1% of patients.³ The majority of case reports and systematic reviews detail periorbital or thoracic lesions.⁴ The location on the scalp and lack of association with paraproteinemia make this a rare presentation of NXG. Studies may be warranted to explore any association of SLE with NXG if more cases present.

In a multicenter cross-sectional study and systematic review of 235 patients with NXG, 87% were White, 12% were Asian, and only 1% were Black or African American.³ The limited representation of skin of color raises concern for the possibility of missed diagnoses and delays in care. 

Treatment of NXG often is multimodal with use of intravenous immunoglobulin, oral steroids, chlorambucil, melphalan, and other alkylating agents, and response is variable.^3-6 Recent studies show treatment effectiveness with Janus kinase inhibitors in granulomatous dermatitides.^7-9 As our patient was not responding to prior treatments, we decided to try ruxolitinib, and she has continued to improve with it.^10,11 Interestingly, the patient experienced continued improvement with intralesional triamcinolone, which is not often reported in the literature.^2-6 Overall, NXG is an extremely rare condition that requires special care in workup to rule out paraproteinemia and a thoughtful approach to treatment modalities.

To the Editor:

Necrobiotic xanthogranuloma (NXG) is classified as a cutaneous non–Langerhans cell histiocytosis, often seen with monoclonal gammopathy of undetermined significance or multiple myeloma.¹ Clinically, it appears as a red or yellow plaque with occasional ulceration and telangiectasias, most commonly seen periorbitally and on the trunk. On pathology, NXG appears as necrobiosis, giant cells, and various inflammatory cells extending into the subcutaneous tissue.² In this article, we describe a rare presentation of NXG in location and skin type.

A 52-year-old woman with a history of systemic lupus erythematosus (SLE) presented with alopecia and a tender lesion on the scalp of 5 years’ duration (Figure 1). The patient had no history of a similar lesion, and no other lesions were present. A biopsy performed at an outside clinic a few weeks to months prior to the initial presentation to our clinic showed NXG (Figure 2). Evaluation at our clinic revealed a 4x4-cm orange-brown annular plaque on the left parietal scalp. Serum and urine protein electrophoresis studies were negative. The patient reported she was up to date with recommended screenings such as mammography and colonoscopy. 

We started the patient on topical triamcinolone and topical ruxolitinib and administered intralesional triamcinolone. She was already taking hydroxychloroquine and leflunomide for SLE. Three weeks later, she returned with improved symptoms and appearance (Figure 1). She remained on intralesional triamcinolone and ruxolitinib and continues to experience improvement.

Necrobiotic xanthogranuloma is rare and typically is associated with monoclonal gammopathy.² In one study, 83 of 100 of patients with NXG presented with or were found to have a monoclonal gammopathy.² In another study, paraproteinemia was detected in 82.1% of patients.³ The majority of case reports and systematic reviews detail periorbital or thoracic lesions.⁴ The location on the scalp and lack of association with paraproteinemia make this a rare presentation of NXG. Studies may be warranted to explore any association of SLE with NXG if more cases present.

In a multicenter cross-sectional study and systematic review of 235 patients with NXG, 87% were White, 12% were Asian, and only 1% were Black or African American.³ The limited representation of skin of color raises concern for the possibility of missed diagnoses and delays in care. 

Treatment of NXG often is multimodal with use of intravenous immunoglobulin, oral steroids, chlorambucil, melphalan, and other alkylating agents, and response is variable.^3-6 Recent studies show treatment effectiveness with Janus kinase inhibitors in granulomatous dermatitides.^7-9 As our patient was not responding to prior treatments, we decided to try ruxolitinib, and she has continued to improve with it.^10,11 Interestingly, the patient experienced continued improvement with intralesional triamcinolone, which is not often reported in the literature.^2-6 Overall, NXG is an extremely rare condition that requires special care in workup to rule out paraproteinemia and a thoughtful approach to treatment modalities.

As the health care landscape continues to shift, direct care (also known as direct pay) models have emerged as attractive alternatives to traditional insurance-based practice. For dermatology residents poised to enter the workforce, the direct care model offers potential advantages in autonomy, patient relationships, and work-life balance, but not without considerable risks and operational challenges. This article explores the key benefits and drawbacks of starting a direct care dermatology practice, providing a framework to help early-career dermatologists determine whether this path aligns with their personal and professional goals.

The transition from dermatology residency to clinical practice allows for a variety of paths, from large academic institutions to private practice to corporate entities (private equity–owned groups). In recent years, the direct care model has gained traction, particularly among physicians seeking greater autonomy and a more sustainable pace of practice.

Direct care dermatology practices operate outside the constraints of third-party payers, offering patients transparent pricing and direct access to care in exchange for fees paid out of pocket. By eliminating insurance companies as the middleman, it allows for less overhead, longer visits with patients, and increased access to care; however, though this model may seem appealing, direct care practices are not without their own set of challenges, especially amid rising concerns over physician burnout and administrative burden. 

This article explores the key benefits and drawbacks of starting a direct care dermatology practice, providing a framework to help early-career dermatologists determine whether this path aligns with their personal and professional goals.

The Case for Direct Care Dermatology

Autonomy and Control—Perhaps the most compelling advantage of the direct care model is clinical and operational autonomy. Without insurance contracts dictating codes, coverage limitations, and documentation demands, physicians regain full control over their practice—how much time they spend with each patient, what treatments they offer, and how they structure their schedules. This option is ideal for those who want to practice medicine the way they were trained—thoroughly, thoughtfully, and without rushing.

Improved Work-Life Balance—The direct care model allows for smaller patient panels, longer visits, and more flexible hours. In contrast to the high patient volumes required to maintain profitability in insurance-based models, direct care dermatologists often can sustain their practice with a smaller number of daily appointments. This results in reduced administrative overhead and the potential for substantial reduction in burnout, a concern that has been well documented among dermatologists in high-volume settings.^1-3 As a result, physicians are less likely to rush through patient visits or be consumed by concerns of falling behind, ultimately causing them to question their career choice.

Closer Patient Relationships—With fewer patients and longer visits, dermatologists often find the direct care model fosters a stronger therapeutic alliance that can improve treatment adherence, outcomes, and overall patient satisfaction. Additionally, patients often appreciate transparent pricing, the ability to reach their dermatologist more directly, and a sense of being truly seen and heard. This, in turn, can make dermatology more rewarding for the provider.

Entrepreneurial Opportunity—Direct care offers entrepreneurial individuals the chance to build a brand and shape a niche. It also provides the flexibility to explore complementary or alternative practice models.

The Challenges of Going Direct

Despite its appeal, starting a direct care practice is not without substantial risks and hurdles—particularly for residents just out of training. These challenges include financial risks and startup costs, market uncertainty, lack of mentorship or support, and limitations in treating complex dermatologic conditions.

Financial Risk and Startup Costs—Launching any solo practice involves a considerable financial investment up front, including rent, medical equipment, electronic medical record systems, malpractice insurance, marketing, and staffing. In a direct care model, there is the added pressure of building a patient base without the referral stream of insurance contracts. In the first 6 to 12 months, income may be minimal, making this route challenging without savings, a financial cushion, or external funding.

Market Uncertainty—The success of direct care dermatology depends heavily on local market dynamics. In affluent or health-literate communities, patients may be more willing to pay out of pocket for expedited or personalized care; however, in other areas, patients may be unwilling or unable to do so—especially if they are accustomed to using insurance. Physicians may find that some of their patients will choose to see a different dermatologist for certain procedures because it is covered by their insurance.

Lack of Immediate Mentorship or Support—Transitioning from residency to independent practice (in any model) can be difficult. Residency provides a structured, team-based environment with colleagues and mentors at every turn. A solo or small-group direct care practice may feel isolating, especially in the early months. Without senior physicians to consult with on challenging cases or administrative decisions, the learning curve can be steep. Early-career dermatologists must be confident in their clinical acumen and be prepared to seek out alternative mentorship or continuing education opportunities.

Limitations in Complex Medical Dermatology—While direct care excels in most general dermatology visit types (from medical and cosmetic to minor surgical), this model may be less suited for patients requiring complex care coordination. Patients with high-cost conditions such as immunobullous diseases or those needing systemic immunosuppressives may still require referral to academic centers or insurance-covered specialists. Additionally, costlier procedures such as Mohs micrographic surgery may not fit well into a direct pay model, which may limit the scope of practice for direct care dermatologists in this subspecialty.

Considerations for Residents

Before committing to practicing via a direct care model, dermatology residents should reflect on the following:

• Risk tolerance: Are you comfortable navigating the business and financial risk?
• Location: Does your target community have patients willing and able to pay out of pocket?
• Scope of interest: Will a direct care practice align with your clinical passions?
• Support systems: Do you have access to mentors, legal and financial advisors, and operational support?
• Long-term goals: Are you building a lifestyle practice, a scalable business, or a stepping stone to a future opportunity?

Ultimately, the decision to pursue a direct care model requires careful reflection on personal values, financial preparedness, and the unique needs of the community one intends to serve.

Final Thoughts

The direct care dermatology model offers an appealing alternative to traditional practice, especially for those prioritizing autonomy, patient connection, and work-life balance; however, it demands an entrepreneurial spirit as well as careful planning and an acceptance of financial uncertainty—factors that may pose challenges for new graduates. For dermatology residents, the decision to pursue direct care should be grounded in personal values, practical considerations, and a clear understanding of both the opportunities and limitations of this evolving practice model.

As the health care landscape continues to shift, direct care (also known as direct pay) models have emerged as attractive alternatives to traditional insurance-based practice. For dermatology residents poised to enter the workforce, the direct care model offers potential advantages in autonomy, patient relationships, and work-life balance, but not without considerable risks and operational challenges. This article explores the key benefits and drawbacks of starting a direct care dermatology practice, providing a framework to help early-career dermatologists determine whether this path aligns with their personal and professional goals.

The transition from dermatology residency to clinical practice allows for a variety of paths, from large academic institutions to private practice to corporate entities (private equity–owned groups). In recent years, the direct care model has gained traction, particularly among physicians seeking greater autonomy and a more sustainable pace of practice.

Direct care dermatology practices operate outside the constraints of third-party payers, offering patients transparent pricing and direct access to care in exchange for fees paid out of pocket. By eliminating insurance companies as the middleman, it allows for less overhead, longer visits with patients, and increased access to care; however, though this model may seem appealing, direct care practices are not without their own set of challenges, especially amid rising concerns over physician burnout and administrative burden. 

This article explores the key benefits and drawbacks of starting a direct care dermatology practice, providing a framework to help early-career dermatologists determine whether this path aligns with their personal and professional goals.

The Case for Direct Care Dermatology

Autonomy and Control—Perhaps the most compelling advantage of the direct care model is clinical and operational autonomy. Without insurance contracts dictating codes, coverage limitations, and documentation demands, physicians regain full control over their practice—how much time they spend with each patient, what treatments they offer, and how they structure their schedules. This option is ideal for those who want to practice medicine the way they were trained—thoroughly, thoughtfully, and without rushing.

Improved Work-Life Balance—The direct care model allows for smaller patient panels, longer visits, and more flexible hours. In contrast to the high patient volumes required to maintain profitability in insurance-based models, direct care dermatologists often can sustain their practice with a smaller number of daily appointments. This results in reduced administrative overhead and the potential for substantial reduction in burnout, a concern that has been well documented among dermatologists in high-volume settings.^1-3 As a result, physicians are less likely to rush through patient visits or be consumed by concerns of falling behind, ultimately causing them to question their career choice.

Closer Patient Relationships—With fewer patients and longer visits, dermatologists often find the direct care model fosters a stronger therapeutic alliance that can improve treatment adherence, outcomes, and overall patient satisfaction. Additionally, patients often appreciate transparent pricing, the ability to reach their dermatologist more directly, and a sense of being truly seen and heard. This, in turn, can make dermatology more rewarding for the provider.

Entrepreneurial Opportunity—Direct care offers entrepreneurial individuals the chance to build a brand and shape a niche. It also provides the flexibility to explore complementary or alternative practice models.

The Challenges of Going Direct

Despite its appeal, starting a direct care practice is not without substantial risks and hurdles—particularly for residents just out of training. These challenges include financial risks and startup costs, market uncertainty, lack of mentorship or support, and limitations in treating complex dermatologic conditions.

Financial Risk and Startup Costs—Launching any solo practice involves a considerable financial investment up front, including rent, medical equipment, electronic medical record systems, malpractice insurance, marketing, and staffing. In a direct care model, there is the added pressure of building a patient base without the referral stream of insurance contracts. In the first 6 to 12 months, income may be minimal, making this route challenging without savings, a financial cushion, or external funding.

Market Uncertainty—The success of direct care dermatology depends heavily on local market dynamics. In affluent or health-literate communities, patients may be more willing to pay out of pocket for expedited or personalized care; however, in other areas, patients may be unwilling or unable to do so—especially if they are accustomed to using insurance. Physicians may find that some of their patients will choose to see a different dermatologist for certain procedures because it is covered by their insurance.

Lack of Immediate Mentorship or Support—Transitioning from residency to independent practice (in any model) can be difficult. Residency provides a structured, team-based environment with colleagues and mentors at every turn. A solo or small-group direct care practice may feel isolating, especially in the early months. Without senior physicians to consult with on challenging cases or administrative decisions, the learning curve can be steep. Early-career dermatologists must be confident in their clinical acumen and be prepared to seek out alternative mentorship or continuing education opportunities.

Limitations in Complex Medical Dermatology—While direct care excels in most general dermatology visit types (from medical and cosmetic to minor surgical), this model may be less suited for patients requiring complex care coordination. Patients with high-cost conditions such as immunobullous diseases or those needing systemic immunosuppressives may still require referral to academic centers or insurance-covered specialists. Additionally, costlier procedures such as Mohs micrographic surgery may not fit well into a direct pay model, which may limit the scope of practice for direct care dermatologists in this subspecialty.

Considerations for Residents

Before committing to practicing via a direct care model, dermatology residents should reflect on the following:

• Risk tolerance: Are you comfortable navigating the business and financial risk?
• Location: Does your target community have patients willing and able to pay out of pocket?
• Scope of interest: Will a direct care practice align with your clinical passions?
• Support systems: Do you have access to mentors, legal and financial advisors, and operational support?
• Long-term goals: Are you building a lifestyle practice, a scalable business, or a stepping stone to a future opportunity?

Ultimately, the decision to pursue a direct care model requires careful reflection on personal values, financial preparedness, and the unique needs of the community one intends to serve.

Final Thoughts

The direct care dermatology model offers an appealing alternative to traditional practice, especially for those prioritizing autonomy, patient connection, and work-life balance; however, it demands an entrepreneurial spirit as well as careful planning and an acceptance of financial uncertainty—factors that may pose challenges for new graduates. For dermatology residents, the decision to pursue direct care should be grounded in personal values, practical considerations, and a clear understanding of both the opportunities and limitations of this evolving practice model.

As the health care landscape continues to shift, direct care (also known as direct pay) models have emerged as attractive alternatives to traditional insurance-based practice. For dermatology residents poised to enter the workforce, the direct care model offers potential advantages in autonomy, patient relationships, and work-life balance, but not without considerable risks and operational challenges. This article explores the key benefits and drawbacks of starting a direct care dermatology practice, providing a framework to help early-career dermatologists determine whether this path aligns with their personal and professional goals.

The transition from dermatology residency to clinical practice allows for a variety of paths, from large academic institutions to private practice to corporate entities (private equity–owned groups). In recent years, the direct care model has gained traction, particularly among physicians seeking greater autonomy and a more sustainable pace of practice.

Direct care dermatology practices operate outside the constraints of third-party payers, offering patients transparent pricing and direct access to care in exchange for fees paid out of pocket. By eliminating insurance companies as the middleman, it allows for less overhead, longer visits with patients, and increased access to care; however, though this model may seem appealing, direct care practices are not without their own set of challenges, especially amid rising concerns over physician burnout and administrative burden. 

This article explores the key benefits and drawbacks of starting a direct care dermatology practice, providing a framework to help early-career dermatologists determine whether this path aligns with their personal and professional goals.

The Case for Direct Care Dermatology

Autonomy and Control—Perhaps the most compelling advantage of the direct care model is clinical and operational autonomy. Without insurance contracts dictating codes, coverage limitations, and documentation demands, physicians regain full control over their practice—how much time they spend with each patient, what treatments they offer, and how they structure their schedules. This option is ideal for those who want to practice medicine the way they were trained—thoroughly, thoughtfully, and without rushing.

Improved Work-Life Balance—The direct care model allows for smaller patient panels, longer visits, and more flexible hours. In contrast to the high patient volumes required to maintain profitability in insurance-based models, direct care dermatologists often can sustain their practice with a smaller number of daily appointments. This results in reduced administrative overhead and the potential for substantial reduction in burnout, a concern that has been well documented among dermatologists in high-volume settings.^1-3 As a result, physicians are less likely to rush through patient visits or be consumed by concerns of falling behind, ultimately causing them to question their career choice.

Closer Patient Relationships—With fewer patients and longer visits, dermatologists often find the direct care model fosters a stronger therapeutic alliance that can improve treatment adherence, outcomes, and overall patient satisfaction. Additionally, patients often appreciate transparent pricing, the ability to reach their dermatologist more directly, and a sense of being truly seen and heard. This, in turn, can make dermatology more rewarding for the provider.

Entrepreneurial Opportunity—Direct care offers entrepreneurial individuals the chance to build a brand and shape a niche. It also provides the flexibility to explore complementary or alternative practice models.

The Challenges of Going Direct

Despite its appeal, starting a direct care practice is not without substantial risks and hurdles—particularly for residents just out of training. These challenges include financial risks and startup costs, market uncertainty, lack of mentorship or support, and limitations in treating complex dermatologic conditions.

Financial Risk and Startup Costs—Launching any solo practice involves a considerable financial investment up front, including rent, medical equipment, electronic medical record systems, malpractice insurance, marketing, and staffing. In a direct care model, there is the added pressure of building a patient base without the referral stream of insurance contracts. In the first 6 to 12 months, income may be minimal, making this route challenging without savings, a financial cushion, or external funding.

Market Uncertainty—The success of direct care dermatology depends heavily on local market dynamics. In affluent or health-literate communities, patients may be more willing to pay out of pocket for expedited or personalized care; however, in other areas, patients may be unwilling or unable to do so—especially if they are accustomed to using insurance. Physicians may find that some of their patients will choose to see a different dermatologist for certain procedures because it is covered by their insurance.

Lack of Immediate Mentorship or Support—Transitioning from residency to independent practice (in any model) can be difficult. Residency provides a structured, team-based environment with colleagues and mentors at every turn. A solo or small-group direct care practice may feel isolating, especially in the early months. Without senior physicians to consult with on challenging cases or administrative decisions, the learning curve can be steep. Early-career dermatologists must be confident in their clinical acumen and be prepared to seek out alternative mentorship or continuing education opportunities.

Limitations in Complex Medical Dermatology—While direct care excels in most general dermatology visit types (from medical and cosmetic to minor surgical), this model may be less suited for patients requiring complex care coordination. Patients with high-cost conditions such as immunobullous diseases or those needing systemic immunosuppressives may still require referral to academic centers or insurance-covered specialists. Additionally, costlier procedures such as Mohs micrographic surgery may not fit well into a direct pay model, which may limit the scope of practice for direct care dermatologists in this subspecialty.

Considerations for Residents

Before committing to practicing via a direct care model, dermatology residents should reflect on the following:

• Risk tolerance: Are you comfortable navigating the business and financial risk?
• Location: Does your target community have patients willing and able to pay out of pocket?
• Scope of interest: Will a direct care practice align with your clinical passions?
• Support systems: Do you have access to mentors, legal and financial advisors, and operational support?
• Long-term goals: Are you building a lifestyle practice, a scalable business, or a stepping stone to a future opportunity?

Ultimately, the decision to pursue a direct care model requires careful reflection on personal values, financial preparedness, and the unique needs of the community one intends to serve.

Final Thoughts

The direct care dermatology model offers an appealing alternative to traditional practice, especially for those prioritizing autonomy, patient connection, and work-life balance; however, it demands an entrepreneurial spirit as well as careful planning and an acceptance of financial uncertainty—factors that may pose challenges for new graduates. For dermatology residents, the decision to pursue direct care should be grounded in personal values, practical considerations, and a clear understanding of both the opportunities and limitations of this evolving practice model.