Pemphigus Vulgaris Successfully Treated With Doxycycline Monotherapy

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Pemphigus Vulgaris Successfully Treated With Doxycycline Monotherapy

To the Editor:

Pemphigus vulgaris (PV) is an acquired autoimmune bullous disease with notable morbidity and mortality if not treated appropriately due to loss of epidermal barrier function and subsequent infection and loss of body fluids. Although the use of systemic corticosteroids and immunosuppressive agents has improved the prognosis, these drugs also may have severe adverse effects, especially in elderly patients. Hence, alternative and safer therapies with anti-inflammatory and immunomodulatory agents such as tetracyclines and nicotinamide have been used with variable results. We report a case of PV that was successfully treated with doxycycline.

An 81-year-old man presented with well-demarcated erosions with overlying yellow crust as well as vesicles and pustules on the scalp (Figure 1A), forehead, bilateral cheeks, and upper back (Figure 1B) of 6 months’ duration. He used topical fluorouracil in the month prior to presentation for suspected actinic keratosis but had stopped its use after 2 weeks. At the first visit, a diagnosis of a reaction to topical fluorouracil with secondary bacterial infection was made and he was prescribed doxycycline hyclate 100 mg twice daily. The patient returned 4 weeks later for follow-up and reported initial notable improvement with subsequent worsening of lesions after he ran out of doxycycline. On physical examination the lesions had considerably improved from the last visit, but he still had a few erosions on the scalp and a few in the oral mucosa. A 1-cm shallow erosion with minimal surrounding erythema on the forehead was present, along with fewer scattered, edematous, erythematous plaques on the back and chest. Pemphigus vulgaris was suspected and 2 shave biopsies from the lesions on the back and cheek were obtained for confirmation. Histopathologic examination revealed epidermal hyperplasia and suprabasal acantholysis as well as moderate perivascular and perifollicular lymphocytic infiltrate with several eosinophils and plasma cells, characteristic of PV (Figure 2). Direct immunofluorescence showed moderate intercellular deposition of IgG within the basal layer and to a lesser extent within suprabasal layers as well as moderate intercellular deposition of C3 within the basal layer, characteristic of PV. IgA and IgM were not present. Indirect immunofluorescence using monkey esophagus revealed no antibodies against the intercellular space of the basement membrane zone. Due to the dramatic response, he continued on doxycycline 100 mg twice daily and remained in complete remission. Ten months after initiating treatment he discontinued doxycycline for 2 days and developed a 1-cm lesion on the left cheek. He resumed treatment with clearing of lesions and was slowly tapered to 50 mg of doxycycline once daily, remaining in complete remission (Figure 3). Doxycycline was discontinued 16 months after initiation; he has remained clear at 13 weeks.

Figure 1. Initial presentation showed well-demarcated erosions with overlying yellow crust as well as vesicles and pustules on the scalp (A) and upper back (B).

Figure 2. Histopathology showed epidermal hyperplasia and suprabasal acantholysis (H&E, original magnification ×40).

Figure 3. Treatment with doxycycline resulted in complete remission of the lesions on the scalp (A) and upper back (B).

The treatment of PV is challenging given the multiple side effects of steroids, especially in elderly patients. Tetracyclines have an advantageous side-effect profile and they have been shown to be efficacious in treating PV when combined with nicotinamide or when used as adjuvant therapy to steroids.1-3 Our case shows a patient who was treated exclusively with doxycycline and achieved complete remission.

 

 

Tetracyclines have multiple biological activities in addition to their antimicrobial function that may provide a therapeutic benefit in PV. They possess immunomodulatory and anti-inflammatory effects by inhibiting leukocyte chemotaxis and activation4-8 and inhibiting cytokine release. They inhibit matrix metalloproteinases, which are the major enzymes responsible for breakdown of the extracellular matrix,9 and they indirectly inhibit neutrophil elastase by protecting α1-protease inhibitor from matrix metalloproteinase degradation.10 Additionally, tetracyclines increase the cohesion of the dermoepidermal junction11; whether they increase the adhesion between epidermal cells is unknown. It has been determined that CD4+ T cells play an essential role in the pathogenesis of PV by promoting anti-desmoglein 3 antibody production.12 Szeto et al13 reported that minocycline, a member of the tetracycline family, has suppressive effects on CD4+ T-cell activation by hindering the activation of nuclear factor of activated T cells (NFAT), a key regulatory factor in T-cell activation. We hypothesize that doxycycline exerted what appears to be immunomodulatory properties in our patient by suppressing CD4+ T-cell activity.

In conclusion, tetracyclines can be an effective and promising therapy for PV given their relatively few side effects and immunomodulating properties. However, further randomized controlled trials will be important to support our conclusion.

References
  1. Chaffins ML, Collison D, Fivenson DP. Treatment of pemphigus and linear IgA dermatosis with nicotinamide and tetracycline: a review of 13 cases. J Am Acad Dermatol. 1993;28:998-1000.
  2. Caelbotta A, Saenz AM, Gonzalez F, et al. Pemphigus vulgaris: benefits of tetracycline as adjuvant therapy in series of thirteen patients. Int J Dermatol. 1999;38:217-221.
  3. McCarty M, Fivenson D. Two decades of using the combination of tetracycline derivatives and niacinamide as steroid-sparing agents in the management of pemphigus defining a niche for these low toxicity agents. J Am Acad Dermatol. 2014;71:475-479.
  4. Majeski JA, McClellan MA, Alexander JW. Effect of antibiotics on the in vitro neutrophil chemotactic response. Am Surg. 1976;42:785-788.
  5. Esterly NB, Furley NL, Flanagan LE. The effect of antimicrobial agents on leukocyte chemotaxis. J Invest Dermatol. 1978;70:51-55.
  6. Gabler WL, Creamer HR. Suppression of human neutrophil functions by tetracyclines. J Periodontal Res. 1991;26:52-58.
  7. Esterly NB, Koransky JS, Furey NL, et al. Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy. Arch Dermatol. 1984;120:1308-1313.
  8. Sapadin AN, Fleischmajer R. Tetracyclines: nonantibiotic properties and their clinical implications. J Am Acad Dermatol. 2006;54:258-265.
  9. Monk E, Shalita A, Siegel DM. Clinical applications of non-antimicrobial tetracyclines in dermatology. Pharmacol Res. 2011;63:130-145.
  10. Golub LM, Evans RT, McNamara TF, et al. A nonantimicrobial tetracycline inhibits gingival matrix metalloproteinases and bone loss in Porphyromonas gingivalis–induced periodontitis in rats. Ann N Y Acad Sci. 1994;732:96-111.
  11. Humbert P, Treffel P, Chapius JF, et al. The tetracyclines in dermatology. J Am Acad Dermatol. 1991;25:691-697.
  12. Nishifuji K, Amagai M, Kuwana M, et al. Detection of antigen-specific B cells in patients with pemphigus vulgaris by enzyme-linked immunospot assay: requirement of T cell collaboration for autoantibody production. J Invest Dermatol. 2000;114:88-94.
  13. Szeto GL, Pomerantz JL, Graham DRM, et al. Minocycline suppresses activation of nuclear factor of activated T cells 1 (NFAT1) in human CD4 T Cells. J Biol Chem. 2011;286:11275-11282.
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Correspondence: Diya F. Mutasim, MD, University of Cincinnati, Department of Dermatology, 231 Albert Sabin Way, PO Box 670592, Cincinnati, OH 45267-0592 (diya.mutasim@uc.edu).

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To the Editor:

Pemphigus vulgaris (PV) is an acquired autoimmune bullous disease with notable morbidity and mortality if not treated appropriately due to loss of epidermal barrier function and subsequent infection and loss of body fluids. Although the use of systemic corticosteroids and immunosuppressive agents has improved the prognosis, these drugs also may have severe adverse effects, especially in elderly patients. Hence, alternative and safer therapies with anti-inflammatory and immunomodulatory agents such as tetracyclines and nicotinamide have been used with variable results. We report a case of PV that was successfully treated with doxycycline.

An 81-year-old man presented with well-demarcated erosions with overlying yellow crust as well as vesicles and pustules on the scalp (Figure 1A), forehead, bilateral cheeks, and upper back (Figure 1B) of 6 months’ duration. He used topical fluorouracil in the month prior to presentation for suspected actinic keratosis but had stopped its use after 2 weeks. At the first visit, a diagnosis of a reaction to topical fluorouracil with secondary bacterial infection was made and he was prescribed doxycycline hyclate 100 mg twice daily. The patient returned 4 weeks later for follow-up and reported initial notable improvement with subsequent worsening of lesions after he ran out of doxycycline. On physical examination the lesions had considerably improved from the last visit, but he still had a few erosions on the scalp and a few in the oral mucosa. A 1-cm shallow erosion with minimal surrounding erythema on the forehead was present, along with fewer scattered, edematous, erythematous plaques on the back and chest. Pemphigus vulgaris was suspected and 2 shave biopsies from the lesions on the back and cheek were obtained for confirmation. Histopathologic examination revealed epidermal hyperplasia and suprabasal acantholysis as well as moderate perivascular and perifollicular lymphocytic infiltrate with several eosinophils and plasma cells, characteristic of PV (Figure 2). Direct immunofluorescence showed moderate intercellular deposition of IgG within the basal layer and to a lesser extent within suprabasal layers as well as moderate intercellular deposition of C3 within the basal layer, characteristic of PV. IgA and IgM were not present. Indirect immunofluorescence using monkey esophagus revealed no antibodies against the intercellular space of the basement membrane zone. Due to the dramatic response, he continued on doxycycline 100 mg twice daily and remained in complete remission. Ten months after initiating treatment he discontinued doxycycline for 2 days and developed a 1-cm lesion on the left cheek. He resumed treatment with clearing of lesions and was slowly tapered to 50 mg of doxycycline once daily, remaining in complete remission (Figure 3). Doxycycline was discontinued 16 months after initiation; he has remained clear at 13 weeks.

Figure 1. Initial presentation showed well-demarcated erosions with overlying yellow crust as well as vesicles and pustules on the scalp (A) and upper back (B).

Figure 2. Histopathology showed epidermal hyperplasia and suprabasal acantholysis (H&E, original magnification ×40).

Figure 3. Treatment with doxycycline resulted in complete remission of the lesions on the scalp (A) and upper back (B).

The treatment of PV is challenging given the multiple side effects of steroids, especially in elderly patients. Tetracyclines have an advantageous side-effect profile and they have been shown to be efficacious in treating PV when combined with nicotinamide or when used as adjuvant therapy to steroids.1-3 Our case shows a patient who was treated exclusively with doxycycline and achieved complete remission.

 

 

Tetracyclines have multiple biological activities in addition to their antimicrobial function that may provide a therapeutic benefit in PV. They possess immunomodulatory and anti-inflammatory effects by inhibiting leukocyte chemotaxis and activation4-8 and inhibiting cytokine release. They inhibit matrix metalloproteinases, which are the major enzymes responsible for breakdown of the extracellular matrix,9 and they indirectly inhibit neutrophil elastase by protecting α1-protease inhibitor from matrix metalloproteinase degradation.10 Additionally, tetracyclines increase the cohesion of the dermoepidermal junction11; whether they increase the adhesion between epidermal cells is unknown. It has been determined that CD4+ T cells play an essential role in the pathogenesis of PV by promoting anti-desmoglein 3 antibody production.12 Szeto et al13 reported that minocycline, a member of the tetracycline family, has suppressive effects on CD4+ T-cell activation by hindering the activation of nuclear factor of activated T cells (NFAT), a key regulatory factor in T-cell activation. We hypothesize that doxycycline exerted what appears to be immunomodulatory properties in our patient by suppressing CD4+ T-cell activity.

In conclusion, tetracyclines can be an effective and promising therapy for PV given their relatively few side effects and immunomodulating properties. However, further randomized controlled trials will be important to support our conclusion.

To the Editor:

Pemphigus vulgaris (PV) is an acquired autoimmune bullous disease with notable morbidity and mortality if not treated appropriately due to loss of epidermal barrier function and subsequent infection and loss of body fluids. Although the use of systemic corticosteroids and immunosuppressive agents has improved the prognosis, these drugs also may have severe adverse effects, especially in elderly patients. Hence, alternative and safer therapies with anti-inflammatory and immunomodulatory agents such as tetracyclines and nicotinamide have been used with variable results. We report a case of PV that was successfully treated with doxycycline.

An 81-year-old man presented with well-demarcated erosions with overlying yellow crust as well as vesicles and pustules on the scalp (Figure 1A), forehead, bilateral cheeks, and upper back (Figure 1B) of 6 months’ duration. He used topical fluorouracil in the month prior to presentation for suspected actinic keratosis but had stopped its use after 2 weeks. At the first visit, a diagnosis of a reaction to topical fluorouracil with secondary bacterial infection was made and he was prescribed doxycycline hyclate 100 mg twice daily. The patient returned 4 weeks later for follow-up and reported initial notable improvement with subsequent worsening of lesions after he ran out of doxycycline. On physical examination the lesions had considerably improved from the last visit, but he still had a few erosions on the scalp and a few in the oral mucosa. A 1-cm shallow erosion with minimal surrounding erythema on the forehead was present, along with fewer scattered, edematous, erythematous plaques on the back and chest. Pemphigus vulgaris was suspected and 2 shave biopsies from the lesions on the back and cheek were obtained for confirmation. Histopathologic examination revealed epidermal hyperplasia and suprabasal acantholysis as well as moderate perivascular and perifollicular lymphocytic infiltrate with several eosinophils and plasma cells, characteristic of PV (Figure 2). Direct immunofluorescence showed moderate intercellular deposition of IgG within the basal layer and to a lesser extent within suprabasal layers as well as moderate intercellular deposition of C3 within the basal layer, characteristic of PV. IgA and IgM were not present. Indirect immunofluorescence using monkey esophagus revealed no antibodies against the intercellular space of the basement membrane zone. Due to the dramatic response, he continued on doxycycline 100 mg twice daily and remained in complete remission. Ten months after initiating treatment he discontinued doxycycline for 2 days and developed a 1-cm lesion on the left cheek. He resumed treatment with clearing of lesions and was slowly tapered to 50 mg of doxycycline once daily, remaining in complete remission (Figure 3). Doxycycline was discontinued 16 months after initiation; he has remained clear at 13 weeks.

Figure 1. Initial presentation showed well-demarcated erosions with overlying yellow crust as well as vesicles and pustules on the scalp (A) and upper back (B).

Figure 2. Histopathology showed epidermal hyperplasia and suprabasal acantholysis (H&E, original magnification ×40).

Figure 3. Treatment with doxycycline resulted in complete remission of the lesions on the scalp (A) and upper back (B).

The treatment of PV is challenging given the multiple side effects of steroids, especially in elderly patients. Tetracyclines have an advantageous side-effect profile and they have been shown to be efficacious in treating PV when combined with nicotinamide or when used as adjuvant therapy to steroids.1-3 Our case shows a patient who was treated exclusively with doxycycline and achieved complete remission.

 

 

Tetracyclines have multiple biological activities in addition to their antimicrobial function that may provide a therapeutic benefit in PV. They possess immunomodulatory and anti-inflammatory effects by inhibiting leukocyte chemotaxis and activation4-8 and inhibiting cytokine release. They inhibit matrix metalloproteinases, which are the major enzymes responsible for breakdown of the extracellular matrix,9 and they indirectly inhibit neutrophil elastase by protecting α1-protease inhibitor from matrix metalloproteinase degradation.10 Additionally, tetracyclines increase the cohesion of the dermoepidermal junction11; whether they increase the adhesion between epidermal cells is unknown. It has been determined that CD4+ T cells play an essential role in the pathogenesis of PV by promoting anti-desmoglein 3 antibody production.12 Szeto et al13 reported that minocycline, a member of the tetracycline family, has suppressive effects on CD4+ T-cell activation by hindering the activation of nuclear factor of activated T cells (NFAT), a key regulatory factor in T-cell activation. We hypothesize that doxycycline exerted what appears to be immunomodulatory properties in our patient by suppressing CD4+ T-cell activity.

In conclusion, tetracyclines can be an effective and promising therapy for PV given their relatively few side effects and immunomodulating properties. However, further randomized controlled trials will be important to support our conclusion.

References
  1. Chaffins ML, Collison D, Fivenson DP. Treatment of pemphigus and linear IgA dermatosis with nicotinamide and tetracycline: a review of 13 cases. J Am Acad Dermatol. 1993;28:998-1000.
  2. Caelbotta A, Saenz AM, Gonzalez F, et al. Pemphigus vulgaris: benefits of tetracycline as adjuvant therapy in series of thirteen patients. Int J Dermatol. 1999;38:217-221.
  3. McCarty M, Fivenson D. Two decades of using the combination of tetracycline derivatives and niacinamide as steroid-sparing agents in the management of pemphigus defining a niche for these low toxicity agents. J Am Acad Dermatol. 2014;71:475-479.
  4. Majeski JA, McClellan MA, Alexander JW. Effect of antibiotics on the in vitro neutrophil chemotactic response. Am Surg. 1976;42:785-788.
  5. Esterly NB, Furley NL, Flanagan LE. The effect of antimicrobial agents on leukocyte chemotaxis. J Invest Dermatol. 1978;70:51-55.
  6. Gabler WL, Creamer HR. Suppression of human neutrophil functions by tetracyclines. J Periodontal Res. 1991;26:52-58.
  7. Esterly NB, Koransky JS, Furey NL, et al. Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy. Arch Dermatol. 1984;120:1308-1313.
  8. Sapadin AN, Fleischmajer R. Tetracyclines: nonantibiotic properties and their clinical implications. J Am Acad Dermatol. 2006;54:258-265.
  9. Monk E, Shalita A, Siegel DM. Clinical applications of non-antimicrobial tetracyclines in dermatology. Pharmacol Res. 2011;63:130-145.
  10. Golub LM, Evans RT, McNamara TF, et al. A nonantimicrobial tetracycline inhibits gingival matrix metalloproteinases and bone loss in Porphyromonas gingivalis–induced periodontitis in rats. Ann N Y Acad Sci. 1994;732:96-111.
  11. Humbert P, Treffel P, Chapius JF, et al. The tetracyclines in dermatology. J Am Acad Dermatol. 1991;25:691-697.
  12. Nishifuji K, Amagai M, Kuwana M, et al. Detection of antigen-specific B cells in patients with pemphigus vulgaris by enzyme-linked immunospot assay: requirement of T cell collaboration for autoantibody production. J Invest Dermatol. 2000;114:88-94.
  13. Szeto GL, Pomerantz JL, Graham DRM, et al. Minocycline suppresses activation of nuclear factor of activated T cells 1 (NFAT1) in human CD4 T Cells. J Biol Chem. 2011;286:11275-11282.
References
  1. Chaffins ML, Collison D, Fivenson DP. Treatment of pemphigus and linear IgA dermatosis with nicotinamide and tetracycline: a review of 13 cases. J Am Acad Dermatol. 1993;28:998-1000.
  2. Caelbotta A, Saenz AM, Gonzalez F, et al. Pemphigus vulgaris: benefits of tetracycline as adjuvant therapy in series of thirteen patients. Int J Dermatol. 1999;38:217-221.
  3. McCarty M, Fivenson D. Two decades of using the combination of tetracycline derivatives and niacinamide as steroid-sparing agents in the management of pemphigus defining a niche for these low toxicity agents. J Am Acad Dermatol. 2014;71:475-479.
  4. Majeski JA, McClellan MA, Alexander JW. Effect of antibiotics on the in vitro neutrophil chemotactic response. Am Surg. 1976;42:785-788.
  5. Esterly NB, Furley NL, Flanagan LE. The effect of antimicrobial agents on leukocyte chemotaxis. J Invest Dermatol. 1978;70:51-55.
  6. Gabler WL, Creamer HR. Suppression of human neutrophil functions by tetracyclines. J Periodontal Res. 1991;26:52-58.
  7. Esterly NB, Koransky JS, Furey NL, et al. Neutrophil chemotaxis in patients with acne receiving oral tetracycline therapy. Arch Dermatol. 1984;120:1308-1313.
  8. Sapadin AN, Fleischmajer R. Tetracyclines: nonantibiotic properties and their clinical implications. J Am Acad Dermatol. 2006;54:258-265.
  9. Monk E, Shalita A, Siegel DM. Clinical applications of non-antimicrobial tetracyclines in dermatology. Pharmacol Res. 2011;63:130-145.
  10. Golub LM, Evans RT, McNamara TF, et al. A nonantimicrobial tetracycline inhibits gingival matrix metalloproteinases and bone loss in Porphyromonas gingivalis–induced periodontitis in rats. Ann N Y Acad Sci. 1994;732:96-111.
  11. Humbert P, Treffel P, Chapius JF, et al. The tetracyclines in dermatology. J Am Acad Dermatol. 1991;25:691-697.
  12. Nishifuji K, Amagai M, Kuwana M, et al. Detection of antigen-specific B cells in patients with pemphigus vulgaris by enzyme-linked immunospot assay: requirement of T cell collaboration for autoantibody production. J Invest Dermatol. 2000;114:88-94.
  13. Szeto GL, Pomerantz JL, Graham DRM, et al. Minocycline suppresses activation of nuclear factor of activated T cells 1 (NFAT1) in human CD4 T Cells. J Biol Chem. 2011;286:11275-11282.
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Pemphigus Vulgaris Successfully Treated With Doxycycline Monotherapy
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Pemphigus Vulgaris Successfully Treated With Doxycycline Monotherapy
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autoimmune bullous disease; pemphigus vulgaris; doxycycline; tetracycline
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  • The treatment of pemphigus vulgaris (PV) is challenging given the side-effect profile of commonly used systemic medications, including steroids, especially in elderly patients.
  • Tetracyclines have an advantageous side-effect profile and may be efficacious in treating PV.
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Hypopigmented Facial Papules on the Cheeks

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Hypopigmented Facial Papules on the Cheeks

The Diagnosis: Tumor of the Follicular Infundibulum

Histopathologic findings from a facial papule in our patient revealed multifocal hyperplasia of anastomosing follicular infundibular cells with multiple connections to the overlying epidermis (Figure). There was no atypia. Gomori methenamine-silver and periodic acid–Schiff stains for fungi were negative. The combined clinical presentation and histopathologic findings supported the diagnosis of multiple tumor of the follicular infundibulum (TFI).



Tumor of the follicular infundibulum was diagnosed based on a biopsy from the right cheek that revealed multifocal hyperplasia of anastomosing follicular infundibular cells with multiple connections to the overlying epidermis (A and B)(H&E, original magnifications ×40 and ×100).

Tumor of the follicular infundibulum is an uncommon benign neoplasm that was first described in 1961 by Mehregan and Butler.1 The reported frequency is 10 per 100,000 biopsies.2 The majority of cases have been reported as solitary lesions, and multiple TFI are rare.3 Tumor of the follicular infundibulum affects middle-aged and elderly individuals with a female predominance.4 Multiple lesions generally range in number from 10 to 20, but there are few reports of more than 100 lesions.2,3,5,6 The solitary tumors often are initially misdiagnosed as basal cell carcinomas (BCCs) or seborrheic keratosis. Multiple TFI have been described variably as hypopigmented, flesh-colored and pink, flat and slightly depressed macules and thin papules. Sites of predilection include the scalp, face, neck, and upper trunk.2,3,5

There is no histopathologic difference between solitary and multiple TFI. Tumor of the follicular infundibulum displays a characteristic pale platelike proliferation of keratinocytes within the upper dermis attached to the overlying epidermis. The proliferating cells stain positive with periodic acid–Schiff, diastase-digestible glycogen is present in the cells at the base of the tumor, and a thickened network or brushlike pattern of elastic fibers surrounds the periphery of the tumor.1 Tumor of the follicular infundibulum is occasionally discovered incidentally on biopsy and has been observed in the margin of wide excisions of a variety of neoplasms including BCC.7 Based on the close association of TFI and BCC in the same specimens, Weyers et al7 concluded that TFI may be a nonaggressive type of BCC. Cribier and Grosshans2 reported 2 cases of TFI overlying a nevus sebaceous and a fibroma.

Treatment of TFI includes topical keratolytics, topical retinoic acid,5 imiquimod,8 topical steroids, and oral etretinate,6 all of which result in minimal improvement or incomplete resolution. Destructive treatments include cryotherapy, curettage, electrosurgery, laser ablation, and surgical excision, but all may lead to an unacceptable cosmetic result.

References

1. Mehregan AH, Butler JD. A tumor of follicular infundibulum. Arch Dermatol. 1961;83:78-81.

2. Cribier B, Grosshans E. Tumor of the follicular infundibulum: a clinicopathologic study. J Am Acad Dermatol. 1995;33:979-984.

3. Kolenik SA 3rd, Bolognia JL, Castiglione FM Jr, et al. Multiple tumors of the follicular infundibulum. Int J Dermatol. 1996;35:282-284.

4. Ackerman AB, Reddy VB, Soyer HP. Neoplasms With Follicular Differentiation. New York, NY: Ardor Scribendi; 2001.

5. Kossard S, Finley AG, Poyzer K, et al. Eruptive infundibulomas. J Am Acad Dermatol. 1989;21:361-366.

6. Schnitzler L, Civatte J, Robin F, et al. Multiple tumors of the follicular infundibulum with basocellular degeneration. apropos of a case [in French]. Ann Dermatol Venereol. 1987;114:551-556.

7. Weyers W, Horster S, Diaz-Cascajo C. Tumor of follicular infundibulum is basal cell carcinoma. Am J Dermatopathol. 2009;31:634-641.

8. Martin JE, Hsu M, Wang LC. An unusual clinical presentation of multiple tumors of the follicular infundibulum. J Am Acad Dermatol. 2009;60:885-886.

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Correspondence: Diya F. Mutasim, MD, Department of Dermatology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0592 (diya.mutasim@uc.edu).

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Correspondence: Diya F. Mutasim, MD, Department of Dermatology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0592 (diya.mutasim@uc.edu).

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The Diagnosis: Tumor of the Follicular Infundibulum

Histopathologic findings from a facial papule in our patient revealed multifocal hyperplasia of anastomosing follicular infundibular cells with multiple connections to the overlying epidermis (Figure). There was no atypia. Gomori methenamine-silver and periodic acid–Schiff stains for fungi were negative. The combined clinical presentation and histopathologic findings supported the diagnosis of multiple tumor of the follicular infundibulum (TFI).



Tumor of the follicular infundibulum was diagnosed based on a biopsy from the right cheek that revealed multifocal hyperplasia of anastomosing follicular infundibular cells with multiple connections to the overlying epidermis (A and B)(H&E, original magnifications ×40 and ×100).

Tumor of the follicular infundibulum is an uncommon benign neoplasm that was first described in 1961 by Mehregan and Butler.1 The reported frequency is 10 per 100,000 biopsies.2 The majority of cases have been reported as solitary lesions, and multiple TFI are rare.3 Tumor of the follicular infundibulum affects middle-aged and elderly individuals with a female predominance.4 Multiple lesions generally range in number from 10 to 20, but there are few reports of more than 100 lesions.2,3,5,6 The solitary tumors often are initially misdiagnosed as basal cell carcinomas (BCCs) or seborrheic keratosis. Multiple TFI have been described variably as hypopigmented, flesh-colored and pink, flat and slightly depressed macules and thin papules. Sites of predilection include the scalp, face, neck, and upper trunk.2,3,5

There is no histopathologic difference between solitary and multiple TFI. Tumor of the follicular infundibulum displays a characteristic pale platelike proliferation of keratinocytes within the upper dermis attached to the overlying epidermis. The proliferating cells stain positive with periodic acid–Schiff, diastase-digestible glycogen is present in the cells at the base of the tumor, and a thickened network or brushlike pattern of elastic fibers surrounds the periphery of the tumor.1 Tumor of the follicular infundibulum is occasionally discovered incidentally on biopsy and has been observed in the margin of wide excisions of a variety of neoplasms including BCC.7 Based on the close association of TFI and BCC in the same specimens, Weyers et al7 concluded that TFI may be a nonaggressive type of BCC. Cribier and Grosshans2 reported 2 cases of TFI overlying a nevus sebaceous and a fibroma.

Treatment of TFI includes topical keratolytics, topical retinoic acid,5 imiquimod,8 topical steroids, and oral etretinate,6 all of which result in minimal improvement or incomplete resolution. Destructive treatments include cryotherapy, curettage, electrosurgery, laser ablation, and surgical excision, but all may lead to an unacceptable cosmetic result.

The Diagnosis: Tumor of the Follicular Infundibulum

Histopathologic findings from a facial papule in our patient revealed multifocal hyperplasia of anastomosing follicular infundibular cells with multiple connections to the overlying epidermis (Figure). There was no atypia. Gomori methenamine-silver and periodic acid–Schiff stains for fungi were negative. The combined clinical presentation and histopathologic findings supported the diagnosis of multiple tumor of the follicular infundibulum (TFI).



Tumor of the follicular infundibulum was diagnosed based on a biopsy from the right cheek that revealed multifocal hyperplasia of anastomosing follicular infundibular cells with multiple connections to the overlying epidermis (A and B)(H&E, original magnifications ×40 and ×100).

Tumor of the follicular infundibulum is an uncommon benign neoplasm that was first described in 1961 by Mehregan and Butler.1 The reported frequency is 10 per 100,000 biopsies.2 The majority of cases have been reported as solitary lesions, and multiple TFI are rare.3 Tumor of the follicular infundibulum affects middle-aged and elderly individuals with a female predominance.4 Multiple lesions generally range in number from 10 to 20, but there are few reports of more than 100 lesions.2,3,5,6 The solitary tumors often are initially misdiagnosed as basal cell carcinomas (BCCs) or seborrheic keratosis. Multiple TFI have been described variably as hypopigmented, flesh-colored and pink, flat and slightly depressed macules and thin papules. Sites of predilection include the scalp, face, neck, and upper trunk.2,3,5

There is no histopathologic difference between solitary and multiple TFI. Tumor of the follicular infundibulum displays a characteristic pale platelike proliferation of keratinocytes within the upper dermis attached to the overlying epidermis. The proliferating cells stain positive with periodic acid–Schiff, diastase-digestible glycogen is present in the cells at the base of the tumor, and a thickened network or brushlike pattern of elastic fibers surrounds the periphery of the tumor.1 Tumor of the follicular infundibulum is occasionally discovered incidentally on biopsy and has been observed in the margin of wide excisions of a variety of neoplasms including BCC.7 Based on the close association of TFI and BCC in the same specimens, Weyers et al7 concluded that TFI may be a nonaggressive type of BCC. Cribier and Grosshans2 reported 2 cases of TFI overlying a nevus sebaceous and a fibroma.

Treatment of TFI includes topical keratolytics, topical retinoic acid,5 imiquimod,8 topical steroids, and oral etretinate,6 all of which result in minimal improvement or incomplete resolution. Destructive treatments include cryotherapy, curettage, electrosurgery, laser ablation, and surgical excision, but all may lead to an unacceptable cosmetic result.

References

1. Mehregan AH, Butler JD. A tumor of follicular infundibulum. Arch Dermatol. 1961;83:78-81.

2. Cribier B, Grosshans E. Tumor of the follicular infundibulum: a clinicopathologic study. J Am Acad Dermatol. 1995;33:979-984.

3. Kolenik SA 3rd, Bolognia JL, Castiglione FM Jr, et al. Multiple tumors of the follicular infundibulum. Int J Dermatol. 1996;35:282-284.

4. Ackerman AB, Reddy VB, Soyer HP. Neoplasms With Follicular Differentiation. New York, NY: Ardor Scribendi; 2001.

5. Kossard S, Finley AG, Poyzer K, et al. Eruptive infundibulomas. J Am Acad Dermatol. 1989;21:361-366.

6. Schnitzler L, Civatte J, Robin F, et al. Multiple tumors of the follicular infundibulum with basocellular degeneration. apropos of a case [in French]. Ann Dermatol Venereol. 1987;114:551-556.

7. Weyers W, Horster S, Diaz-Cascajo C. Tumor of follicular infundibulum is basal cell carcinoma. Am J Dermatopathol. 2009;31:634-641.

8. Martin JE, Hsu M, Wang LC. An unusual clinical presentation of multiple tumors of the follicular infundibulum. J Am Acad Dermatol. 2009;60:885-886.

References

1. Mehregan AH, Butler JD. A tumor of follicular infundibulum. Arch Dermatol. 1961;83:78-81.

2. Cribier B, Grosshans E. Tumor of the follicular infundibulum: a clinicopathologic study. J Am Acad Dermatol. 1995;33:979-984.

3. Kolenik SA 3rd, Bolognia JL, Castiglione FM Jr, et al. Multiple tumors of the follicular infundibulum. Int J Dermatol. 1996;35:282-284.

4. Ackerman AB, Reddy VB, Soyer HP. Neoplasms With Follicular Differentiation. New York, NY: Ardor Scribendi; 2001.

5. Kossard S, Finley AG, Poyzer K, et al. Eruptive infundibulomas. J Am Acad Dermatol. 1989;21:361-366.

6. Schnitzler L, Civatte J, Robin F, et al. Multiple tumors of the follicular infundibulum with basocellular degeneration. apropos of a case [in French]. Ann Dermatol Venereol. 1987;114:551-556.

7. Weyers W, Horster S, Diaz-Cascajo C. Tumor of follicular infundibulum is basal cell carcinoma. Am J Dermatopathol. 2009;31:634-641.

8. Martin JE, Hsu M, Wang LC. An unusual clinical presentation of multiple tumors of the follicular infundibulum. J Am Acad Dermatol. 2009;60:885-886.

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Cutis - 94(5)
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Cutis - 94(5)
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E1-E3
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E1-E3
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Hypopigmented Facial Papules on the Cheeks
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Hypopigmented Facial Papules on the Cheeks
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adnexal tumors, hypopigmentation
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adnexal tumors, hypopigmentation
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A 73-year-old woman presented with multiple mildly pruritic, hypopigmented, thin papules involving both cheeks of 5 months’ duration. The patient had no improvement with ketoconazole cream 2% and hydrocortisone cream 1% used daily for 1 month for presumed tinea versicolor. Physical examination revealed 10 ill-defined, 2- to 5-mm, round and oval, smooth hypopigmented, slightly raised papules located on the lower aspect of both cheeks.
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