Long-standing Pseudoatrophoderma Colli Successfully Treated With Minocycline

Pseudoatrophoderma colli (PADC) is a rare, persistent dermatosis characterized by hyperpigmented plaques and macules with a finely wrinkled atrophic appearance most often involving the neck and upper trunk.¹ It was first described in 1934 by Becker and Muir, who reported a female patient who had presented with what at first appeared to be vitiligo.² They coined the term pseudoatrophoderma colli: “pseudoatrophoderma” due to its initial impression of atrophy without actual histologic evidence thereof, and “colli” because of its original presentation on the neck and upper chest. Following their inchoate description, there have been exceedingly few cases reported in the literature, most being in female patients. Contrary to the apparent trend of the documented cases, however, we postulate PADC is more common and underreported. Furthermore, we suspect the gender predilection may be more coincidental than definitive.

Case Report
Our patient initially presented to his primary care physician with a long-standing skin condition, reportedly present for many years, stating that a previous doctor had diagnosed him with tinea versicolor. The patient described his symptoms as worsening in the winter with comparable improvement in the summer months. Physical exam revealed multiple coalescing dark patches approximately 0.5 to 1 cm in diameter over the trunk, shoulders, and bilateral deltoid regions. Treatment with emollients was unsuccessful, and the lesions progressed further, eventually reaching his neck, face, and extremities (Figures 1 and 2). He was subsequently referred to a dermatologist who diagnosed tinea versicolor and prescribed itraconazole, though treatment was without improvement.

Biopsy revealed a loss of granular layer as well as compact orthokeratosis throughout the stratum corneum, consistent with ichthyosis. A workup for both acquired and congenital ichthyosis was negative. The patient was brought to grand rounds, and the diagnosis of PADC was made. Subsequent initiation of 100 mg of minocycline daily resolved the patient’s symptoms.

Literature Review
Literature review found there have been fewer than 20 case reports of PADC published from 1934 to the present day. The original PADC patient, described by Becker and Muir,² was a young woman of Jewish heritage who, along with her sister, had first noticed skin lesions 4 years prior to her initial visit. Similar to our patient, her lesions waxed and waned with the seasons and had initially been diagnosed as tinea versicolor.² The apparent second reported case was presented before the San Francisco Dermatological Society the following year, and another two cases, incidentally sisters, were written about in the Archives of Dermotology and Syphilology in 1939 by Frost and Epstein.³ In 1954, a 31-year-old woman was diagnosed with PADC and reported by Ayres and Ayres,⁴ and, in 1955, a 45-year-old woman, whose symptoms had persisted for 14 years, with PADC presented to Obermayer and Becker.⁵ Five new cases were then reported in 1957, all by Kesten and James.⁶ One of these five new patients was male, representing the first male with PADC published. In 1969, the second male case was reported,⁷ and a familial case of three patients was published in 1980.⁸ Finally, the most recent case, another male, was reported by Brazilian dermatologist Neto in 1987.⁹

The article by Kesten and James⁶ summarized the histologic findings in seven patients. They noted the epidermis to be edematous and wavy with alternate thinning and thickening of the corium. There was occasional keratotic plugging of hair follicles along with some intermittent parakeratosis and thinning of the granular layer. Acanthosis was present in some areas and in some, there were vacuolated and pyknotic prickle cells. The dermis had dilated superficial blood vessels with little perivascular lymphocytic infiltration. Elastic tissue fragmentation was absent in all but one of their five patients.⁶ 

There has been discussion about the relationship between PADC, confluent and reticulate papillomatosis (CRP), ichthyosis vulgaris (IV), and pseudoacanthosis nigricans (PAN).^6,8,9,10 Waisman¹⁰ argued that PAN and CRP were the same entity based on similarities in clinical appearance and histological findings. CRP begins in adolescence and young adulthood around the anterior chest with eruptions composed of small gray papules coalescing into plaques in the long axis of the anterior trunk, mid back, axillae, and neck.¹⁰ Similarly, PADC is most often first noted on the upper chest and neck with similar macroscopic appearance. In truth, many dermatologists have considered PADC to be a variant of CRP.⁶ In the article by Kesten and James,⁶ a number of cases of individuals with CRP who also had histologic findings consistent with both PAN and PADC were reviewed. This led the authors⁶ to believe that PADC was a subvariety or transitional phase of CRP and may also have some relationship to PAN. In addition to its possible relationship to CRP and PAN, PADC also shares characteristics with ichthyosiform dermatoses and should be on one’s differential diagnosis.³

Over the years numerous treatment regimens have been proposed. Obermayer and Becker⁵ considered the condition secondary to a vitamin deficiency (specifically, vitamin A). Both Kesten and James⁶ and Ayres and Ayres⁴ prescribed local and systemic vitamin A treatment. Kesten and James⁶ had no success, while Ayres and Ayres⁵ reported moderate clearing of the lesions. Keratolytics, quartz lamps, topical corticosteroids, superficial radiation,¹ and alpha hydroxy acids⁴ have also been used in the past with varying degrees of success. The current recommended therapy is minocycline,¹ a synthetic tetracycline derivative first discovered in 1966. While its mechanism of action as an antibiotic is the inhibition of bacterial protein synthesis by binding the 30S ribosomal subunit (and possibly the 50S ribosomal subunit as well) of susceptible bacteria, it also has anti-inflammatory properties.¹¹ It is unknown how this affects patients with PADC, but as with our patient and others with CRP,^12-14 minocycline has been shown to be an effective therapeutic option. It is speculated that the anti-inflammatory properties of the antibiotic, for example inhibition of neutrophil migration and reactive oxygen release, may be responsible for its clinical efficacy, as no causal bacteria are linked to PADC or CRP cases.

Despite the paucity of cases reported in the literature, the similarity of PADC to PAN, CRP, and IV, along with its general rarity, likely contribute to clinicians missing its diagnosis. Therefore, it is plausible PADC is underreported as few health care providers outside of dermatology are likely even aware of the condition. In the same light, given that CRP and PADC have the same recommended therapy (minocycline), improper diagnosis with proper therapy could contribute to the underreporting of PADC. If PADC is in fact a subvariety or transitional phase of CRP as Kesten and James⁶ proposed, clinicians may be primarily seeing patients after PADC has transitioned to CRP, therefore missing their opportunity for diagnosis. 

Initially following PADC’s original description by Becker and Muir,² it was only found in female patients.¹⁰ Since the Kesten and James⁶ case report in 1957, however, at least three cases have been reported in men, and our case makes a fourth. This means more than 25% of PADC cases are in men. As previously postulated, PADC is likely related to CRP. If this is in fact the case, it further supports our theory of PADC’s coincidental female gender predilection because CRP is actually found more often in men.¹⁰

Conclusions
This case report is an example of the successful treatment of a patient suffering from PADC with minocycline. It helps further support the current protocol for treatment of PADC. To the best of the authors’ knowledge, this is also the first report of a patient with PADC in 30 years. While this may be due to fewer patients with the condition, it is the authors’ opinion that it is instead simply underreported and misdiagnosed. Finally, this case report marks the fourth incidence of a case of a male patient with PADC. The growing number of male patients as well as the likely relationship between CARP and PADC contribute further to our theory of its improperly labeled gender predilection. If gender partiality does exist, it is likely weaker than previously thought.

Dr Clement is the regent medical officer at School of Infantry  - West in Camp Pendleton, CA. Dr Handfield is director of the National Capital Consortium Dermatology Residency Program and chief of integrative dermatology at Walter Reed National Military Medical Center in Bethesda, MD.

Disclosure: The authors report no relevant financial relationships.

References
1. James WD, Elston DM, Treat JR, Rosenbach MA, Neuhaus IM. Pityriasis rosea, pityriasis rubra, pilaris, and other papulosquamous and hyperkeratotic diseases. Andrews’ Diseases of the Skin: Clinical Dermatology. 13th ed. Philadelphia, PA: Elsevier; 2019:209.

2. Becker SW, Muir KB. Pseudo-atrophoderma colli: a hitherto undescribed condition. Arch Dermatol Syphilol. 1934;29(1):53-56. doi:10.1001/archderm.1934.01460070056005

3. Frost K, Epstein E. Pseudoatrophoderma colli in sisters. Arch Dermatol Syphilol. 1939;40(5):755-761. doi:10.1001/archderm.1939.01490050071006

4. Jensen AK, Winer LH. Los Angeles Dermatological Society. AMA Arch Dermatol. 1955;71(6):763-770. doi:10.1001/archderm.1955.01540300085024

5. Jensen AK, Winer LH. Los Angeles Dermatological Society. AMA Arch Dermatol. 1955;72(3):281-282. doi:10.1001/archderm.1955.03730330061011

6. Kesten BM, James HD. Pseudoatrophoderma colli, acanthosis nigricans, and confluent and reticular papillomatosis. Arch Dermatol. 1957;75(4):525-542. doi:10.1001/archderm.1957.01550160051007

7. Kanan MW, Kandil E. Pseudoatrophoderma colli in a male. Br J Dermatol. 1969;81(1):65-68. doi: 10.1111/j.1365-2133.1969.tb15921.x

8. Kauh YC, Knepp ME, Luscombe HA. Pseudoatrophoderma colli: a familial case. Arch Dermatol. 1980;116(10):1181-1182. doi:10.1001/archderm.1980.01640340091026

9. Neto AS, Pires MC, Coletta EN. Pseudo-atrofoderma colli e papilomatose confluente e reticulada de gourgerot e carteaud (atrofia brilhante). Med Cutan Ibero Lat Am. 1987;15(6):477-480.

10. Waisman M. Cutaneous papillomatosis, pseudo-acanthosis nigricans, and benign acanthosis nigricans. South Med J. 1953;46(2):162-169. doi: 10.1097/00007611-195302000-00012

11. Garrido-Mesa N, Zarzuelo A, Gálvez J. Minocycline: far beyond an antibiotic. Br J Pharmacol. 2013;169(2):337-352. doi:10.111/bph.12139

12. Lee S, Choi J, Sung K, Moon K, Koh JK. Confluent and reticulated papillomatosis successfully treated with minocycline. Ann Dermatol. 2000;12(1):33-37. doi:10.5021/ad.2000.12.1.33

13. Shimizu S, Han-Yaku H. Confluent and reticulated papillomatosis responsive to minocycline. Dermatology. 1997;194(1):59-61. doi:10.1159/000246059

14. Montemarano AD, Hengge M, Sau P, Welch M. Confluent and reticulated papillomatosis: response to minocycline. J Am Acad Dermatol. 1996;34(2 Pt 1):253-256. doi:10.1016/s0190-9622(96)80120-4

Pseudoatrophoderma colli (PADC) is a rare, persistent dermatosis characterized by hyperpigmented plaques and macules with a finely wrinkled atrophic appearance most often involving the neck and upper trunk.¹ It was first described in 1934 by Becker and Muir, who reported a female patient who had presented with what at first appeared to be vitiligo.² They coined the term pseudoatrophoderma colli: “pseudoatrophoderma” due to its initial impression of atrophy without actual histologic evidence thereof, and “colli” because of its original presentation on the neck and upper chest. Following their inchoate description, there have been exceedingly few cases reported in the literature, most being in female patients. Contrary to the apparent trend of the documented cases, however, we postulate PADC is more common and underreported. Furthermore, we suspect the gender predilection may be more coincidental than definitive.

Case Report
Our patient initially presented to his primary care physician with a long-standing skin condition, reportedly present for many years, stating that a previous doctor had diagnosed him with tinea versicolor. The patient described his symptoms as worsening in the winter with comparable improvement in the summer months. Physical exam revealed multiple coalescing dark patches approximately 0.5 to 1 cm in diameter over the trunk, shoulders, and bilateral deltoid regions. Treatment with emollients was unsuccessful, and the lesions progressed further, eventually reaching his neck, face, and extremities (Figures 1 and 2). He was subsequently referred to a dermatologist who diagnosed tinea versicolor and prescribed itraconazole, though treatment was without improvement.

Biopsy revealed a loss of granular layer as well as compact orthokeratosis throughout the stratum corneum, consistent with ichthyosis. A workup for both acquired and congenital ichthyosis was negative. The patient was brought to grand rounds, and the diagnosis of PADC was made. Subsequent initiation of 100 mg of minocycline daily resolved the patient’s symptoms.

Literature Review
Literature review found there have been fewer than 20 case reports of PADC published from 1934 to the present day. The original PADC patient, described by Becker and Muir,² was a young woman of Jewish heritage who, along with her sister, had first noticed skin lesions 4 years prior to her initial visit. Similar to our patient, her lesions waxed and waned with the seasons and had initially been diagnosed as tinea versicolor.² The apparent second reported case was presented before the San Francisco Dermatological Society the following year, and another two cases, incidentally sisters, were written about in the Archives of Dermotology and Syphilology in 1939 by Frost and Epstein.³ In 1954, a 31-year-old woman was diagnosed with PADC and reported by Ayres and Ayres,⁴ and, in 1955, a 45-year-old woman, whose symptoms had persisted for 14 years, with PADC presented to Obermayer and Becker.⁵ Five new cases were then reported in 1957, all by Kesten and James.⁶ One of these five new patients was male, representing the first male with PADC published. In 1969, the second male case was reported,⁷ and a familial case of three patients was published in 1980.⁸ Finally, the most recent case, another male, was reported by Brazilian dermatologist Neto in 1987.⁹

The article by Kesten and James⁶ summarized the histologic findings in seven patients. They noted the epidermis to be edematous and wavy with alternate thinning and thickening of the corium. There was occasional keratotic plugging of hair follicles along with some intermittent parakeratosis and thinning of the granular layer. Acanthosis was present in some areas and in some, there were vacuolated and pyknotic prickle cells. The dermis had dilated superficial blood vessels with little perivascular lymphocytic infiltration. Elastic tissue fragmentation was absent in all but one of their five patients.⁶ 

There has been discussion about the relationship between PADC, confluent and reticulate papillomatosis (CRP), ichthyosis vulgaris (IV), and pseudoacanthosis nigricans (PAN).^6,8,9,10 Waisman¹⁰ argued that PAN and CRP were the same entity based on similarities in clinical appearance and histological findings. CRP begins in adolescence and young adulthood around the anterior chest with eruptions composed of small gray papules coalescing into plaques in the long axis of the anterior trunk, mid back, axillae, and neck.¹⁰ Similarly, PADC is most often first noted on the upper chest and neck with similar macroscopic appearance. In truth, many dermatologists have considered PADC to be a variant of CRP.⁶ In the article by Kesten and James,⁶ a number of cases of individuals with CRP who also had histologic findings consistent with both PAN and PADC were reviewed. This led the authors⁶ to believe that PADC was a subvariety or transitional phase of CRP and may also have some relationship to PAN. In addition to its possible relationship to CRP and PAN, PADC also shares characteristics with ichthyosiform dermatoses and should be on one’s differential diagnosis.³

Over the years numerous treatment regimens have been proposed. Obermayer and Becker⁵ considered the condition secondary to a vitamin deficiency (specifically, vitamin A). Both Kesten and James⁶ and Ayres and Ayres⁴ prescribed local and systemic vitamin A treatment. Kesten and James⁶ had no success, while Ayres and Ayres⁵ reported moderate clearing of the lesions. Keratolytics, quartz lamps, topical corticosteroids, superficial radiation,¹ and alpha hydroxy acids⁴ have also been used in the past with varying degrees of success. The current recommended therapy is minocycline,¹ a synthetic tetracycline derivative first discovered in 1966. While its mechanism of action as an antibiotic is the inhibition of bacterial protein synthesis by binding the 30S ribosomal subunit (and possibly the 50S ribosomal subunit as well) of susceptible bacteria, it also has anti-inflammatory properties.¹¹ It is unknown how this affects patients with PADC, but as with our patient and others with CRP,^12-14 minocycline has been shown to be an effective therapeutic option. It is speculated that the anti-inflammatory properties of the antibiotic, for example inhibition of neutrophil migration and reactive oxygen release, may be responsible for its clinical efficacy, as no causal bacteria are linked to PADC or CRP cases.

Despite the paucity of cases reported in the literature, the similarity of PADC to PAN, CRP, and IV, along with its general rarity, likely contribute to clinicians missing its diagnosis. Therefore, it is plausible PADC is underreported as few health care providers outside of dermatology are likely even aware of the condition. In the same light, given that CRP and PADC have the same recommended therapy (minocycline), improper diagnosis with proper therapy could contribute to the underreporting of PADC. If PADC is in fact a subvariety or transitional phase of CRP as Kesten and James⁶ proposed, clinicians may be primarily seeing patients after PADC has transitioned to CRP, therefore missing their opportunity for diagnosis. 

Initially following PADC’s original description by Becker and Muir,² it was only found in female patients.¹⁰ Since the Kesten and James⁶ case report in 1957, however, at least three cases have been reported in men, and our case makes a fourth. This means more than 25% of PADC cases are in men. As previously postulated, PADC is likely related to CRP. If this is in fact the case, it further supports our theory of PADC’s coincidental female gender predilection because CRP is actually found more often in men.¹⁰

Conclusions
This case report is an example of the successful treatment of a patient suffering from PADC with minocycline. It helps further support the current protocol for treatment of PADC. To the best of the authors’ knowledge, this is also the first report of a patient with PADC in 30 years. While this may be due to fewer patients with the condition, it is the authors’ opinion that it is instead simply underreported and misdiagnosed. Finally, this case report marks the fourth incidence of a case of a male patient with PADC. The growing number of male patients as well as the likely relationship between CARP and PADC contribute further to our theory of its improperly labeled gender predilection. If gender partiality does exist, it is likely weaker than previously thought.

Dr Clement is the regent medical officer at School of Infantry  - West in Camp Pendleton, CA. Dr Handfield is director of the National Capital Consortium Dermatology Residency Program and chief of integrative dermatology at Walter Reed National Military Medical Center in Bethesda, MD.

Disclosure: The authors report no relevant financial relationships.

References
1. James WD, Elston DM, Treat JR, Rosenbach MA, Neuhaus IM. Pityriasis rosea, pityriasis rubra, pilaris, and other papulosquamous and hyperkeratotic diseases. Andrews’ Diseases of the Skin: Clinical Dermatology. 13th ed. Philadelphia, PA: Elsevier; 2019:209.

2. Becker SW, Muir KB. Pseudo-atrophoderma colli: a hitherto undescribed condition. Arch Dermatol Syphilol. 1934;29(1):53-56. doi:10.1001/archderm.1934.01460070056005

3. Frost K, Epstein E. Pseudoatrophoderma colli in sisters. Arch Dermatol Syphilol. 1939;40(5):755-761. doi:10.1001/archderm.1939.01490050071006

4. Jensen AK, Winer LH. Los Angeles Dermatological Society. AMA Arch Dermatol. 1955;71(6):763-770. doi:10.1001/archderm.1955.01540300085024

5. Jensen AK, Winer LH. Los Angeles Dermatological Society. AMA Arch Dermatol. 1955;72(3):281-282. doi:10.1001/archderm.1955.03730330061011

6. Kesten BM, James HD. Pseudoatrophoderma colli, acanthosis nigricans, and confluent and reticular papillomatosis. Arch Dermatol. 1957;75(4):525-542. doi:10.1001/archderm.1957.01550160051007

7. Kanan MW, Kandil E. Pseudoatrophoderma colli in a male. Br J Dermatol. 1969;81(1):65-68. doi: 10.1111/j.1365-2133.1969.tb15921.x

8. Kauh YC, Knepp ME, Luscombe HA. Pseudoatrophoderma colli: a familial case. Arch Dermatol. 1980;116(10):1181-1182. doi:10.1001/archderm.1980.01640340091026

9. Neto AS, Pires MC, Coletta EN. Pseudo-atrofoderma colli e papilomatose confluente e reticulada de gourgerot e carteaud (atrofia brilhante). Med Cutan Ibero Lat Am. 1987;15(6):477-480.

10. Waisman M. Cutaneous papillomatosis, pseudo-acanthosis nigricans, and benign acanthosis nigricans. South Med J. 1953;46(2):162-169. doi: 10.1097/00007611-195302000-00012

11. Garrido-Mesa N, Zarzuelo A, Gálvez J. Minocycline: far beyond an antibiotic. Br J Pharmacol. 2013;169(2):337-352. doi:10.111/bph.12139

12. Lee S, Choi J, Sung K, Moon K, Koh JK. Confluent and reticulated papillomatosis successfully treated with minocycline. Ann Dermatol. 2000;12(1):33-37. doi:10.5021/ad.2000.12.1.33

13. Shimizu S, Han-Yaku H. Confluent and reticulated papillomatosis responsive to minocycline. Dermatology. 1997;194(1):59-61. doi:10.1159/000246059

14. Montemarano AD, Hengge M, Sau P, Welch M. Confluent and reticulated papillomatosis: response to minocycline. J Am Acad Dermatol. 1996;34(2 Pt 1):253-256. doi:10.1016/s0190-9622(96)80120-4