Confluent and Reticulated Papillomatosis

Back

Background

Gougerot and Carteud originally described confluent and reticulated papillomatosis (CRP) in 1927 under the name papillomatose pigmentée innominée and later renamed it papillomatose pigmentée confluente et réticulée.[1, 2, 3] Confluent and reticulated papillomatosis was subsequently categorized as a new form of cutaneous papillomatosis and diagnostic criteria were established. Wise described the first case in the United States in 1937 and called it confluent and reticular papillomatosis.[4, 5] The existence of confluent and reticulated papillomatosis as a distinct entity was argued for many years because of the clinical and histologic similarities between confluent and reticulated papillomatosis and the different forms of acanthosis nigricans, but the disease is now generally accepted as a distinct entity.[6]

Confluent and reticulated papillomatosis is a rare disease typically affecting young persons. Confluent and reticulated papillomatosis is characterized by grayish blue hyperkeratotic papules, usually located on the trunk. The lesions coalesce to form confluent plaques centrally and a reticular pattern peripherally. Confluent and reticulated papillomatosis may represent an endocrine disturbance, a disorder of keratinization, an abnormal host reaction to fungi or bacteria, a hereditary disorder, or a variant of amyloidosis. The eruption is chronic with exacerbations and remissions. Confluent and reticulated papillomatosis is responsive to treatment but frequently recurs after discontinuation of therapy.

Pathophysiology

Both electron microscopy studies and immunohistochemical analysis of lesions of confluent and reticulated papillomatosis support the concept of abnormal keratinocyte differentiation and maturation. These findings include an increased transition cell layer and increased lamellar granules in the stratum granulosum, along with increased involucrin, keratin 16, and Ki-67 expression.[7] Increased melanosomes in the stratum corneum probably account for the observed pigmentary changes.

Yeastlike spores were evident in 6 of 10 Lebanese cases, supporting a role for Malassezia furfur in the pathogenesis of confluent and reticulated papillomatosis.[8]

Etiology

Theories as to the etiology of confluent and reticulated papillomatosis include an endocrine disturbance, a disorder of keratinization, and an abnormal host reaction to Pityrosporum organisms or bacteria. Reports also exist of familial cases of confluent and reticulated papillomatosis[9, 10, 11, 12] and the possibility of confluent and reticulated papillomatosis representing a variant of amyloidosis.[13]

Endocrine disturbance in confluent and reticulated papillomatosis

Gougerot himself suggested the possibility of an endocrine disturbance having a role in confluent and reticulated papillomatosis. Others have also advanced this theory in light of the common observation of endocrine disturbances in patients with confluent and reticulated papillomatosis (eg, Cushing disease, menstrual irregularities, obesity, abnormal glucose tolerance or diabetes mellitus, thyroid disease, pituitary dysfunction, hirsutism or hypertrichosis). It has been described in at least one patient with hyperthyroidism.[14]

In Japan, 76.5% of cases of confluent and reticulated papillomatosis are associated with obesity or rapid weight gain.

In addition, lesions of confluent and reticulated papillomatosis have been noted to remit during pregnancy or with weight loss.

No single endocrine abnormality is seen; however, in many of the cases, no abnormality exists at all.

Disorder of keratinization in confluent and reticulated papillomatosis

Miescher first proposed that confluent and reticulated papillomatosis is due to a defect in keratinization. This idea is supported by electron microscopic studies, which demonstrate increased lamellar granules in the stratum granulosum, a finding seen in conditions of increased cell turnover and desquamation (eg, psoriasis), and an increased transition cell layer, which represents the zone where granular cells are converted into cornified cells.

The above findings are consistent with immunohistochemical studies of lesions of confluent and reticulated papillomatosis, which demonstrate increased expression of involucrin, keratin 16, and Ki-67—protein markers for keratinocyte differentiation and maturation.

Further evidence for the role of a defect of keratinization is the response of confluent and reticulated papillomatosis to topical and oral retinoids, which are useful in treating such defects. Most recently, confluent and reticulated papillomatosis has been shown to respond to topical analogues of vitamin D, agents that also regulate cell differentiation and inhibit keratinocyte proliferation.

Ultraviolet light exposure and avitaminosis have been associated with the development of confluent and reticulated papillomatosis, as they may trigger or exacerbate the underlying abnormality.[15] It is possible that HIV infection may do the same.[16]

Another interesting association is that of 2 patients with both confluent and reticulated papillomatosis and atopy, a condition where other disorders of keratinization are found.[17]

Fungal infection in confluent and reticulated papillomatosis

Another theory holds that confluent and reticulated papillomatosis represents an abnormal host reaction to Pityrosporum orbiculare, either in the yeast or the hyphal form. This theory is based on the observation that confluent and reticulated papillomatosis is sometimes colonized with Pityrosporum organisms, and clearance occurs with antifungals and the associated eradication of Pityrosporum organisms.

Many cases of confluent and reticulated papillomatosis do not have any evidence of Pityrosporum infection, and fail to respond to antifungal therapy.

In one study, 20 of 31 cases of confluent and reticulated papillomatosis had negative potassium hydroxide examinations, and 14 of 19 patients treated with topical imidazoles failed to respond, with no correlation between potassium hydroxide (KOH) examinations and response to therapy.

In another study, P obiculare was isolated in only 15 of 54 cases, and only 8 of 26 cases improved with antimycotic therapy. Similarly, in Japan, fungus could be detected in only 6 of 44 cases. However, yeastlike spores were evident in 6 of 10 Lebanese cases, supporting a role for Malassezia furfur in the pathogenesis of confluent and reticulated papillomatosis.[8]

A genetic or diet-induced abnormal keratinizing response is suggested to be triggered by P orbiculare.

Bacterial infection in confluent and reticulated papillomatosis

The use of antibiotics in the treatment of confluent and reticulated papillomatosis was introduced after the fortuitous discovery of improvement in a patient who was taking furacycline for arthritis. Since then, an increase has occurred in the number of reports of successful treatment of confluent and reticulated papillomatosis with antibiotics of the tetracycline, macrolide, cephalosporin and (most recently) steroid classes. This finding has lead to the concept that bacteria, perhaps within the hair follicle, are the etiologic agents.

An exciting development in our understanding of the cause of confluent and reticulated papillomatosis is the report of a newly described dietzia strain of Actinomyces, isolated from a patient with confluent and reticulated papillomatosis.[18] Antibiotic minimal inhibitory concentrations suggested sensitivity to tetracycline and erythromycin, and the patient responded to treatment with these medications. The authors of this study propose that confluent and reticulated papillomatosis is probably a reaction pattern to bacterial infection in susceptible individuals, resulting in epidermal proliferation, and have named this A dietzia strain X.

Another explanation for the effectiveness of antibiotics may be the anti-inflammatory and antiproliferative actions of these agents; however, some authors argue that confluent and reticulated papillomatosis is not an inflammatory disorder.

Heredity in confluent and reticulated papillomatosis: Six familial reports of confluent and reticulated papillomatosis have raised the possibility of it being a heritable disorder. These cases include 2 sisters and a brother; 2 sisters and 1 of their daughters; a mother, a daughter, and a son; and 3 sets of brothers, including 1 observed by the authors of this article. This small number of reports does not suggest any particular pattern or mode of inheritance.

Variant of amyloidosis

The report of amyloid in skin lesions of only 3 patients makes this theory unlikely.

Epidemiology

Frequency

The frequency of confluent and reticulated papillomatosis internationally is unknown. It is considered to be rare.

Race

Older reviews report confluent and reticulated papillomatosis being more common among blacks than other races, with a ratio of 2:1, but more recent surveys, including one survey of 90 cases, show a predominance in whites.

Sex

The proportion of women to men affected by confluent and reticulated papillomatosis has been reported to be as high as 2.8:1, but the ratio is probably closer to 1.4:1. The opposite is true in Japan, where confluent and reticulated papillomatosis is more common in men than in women. In one study of 10 Lebanese cases, half were of each sex.[8]

Age

The onset of confluent and reticulated papillomatosis usually occurs shortly after puberty. The mean patient age at onset varies from 18.5-21 years, with a range of 5-63 years. Similarly, the average patient age at onset is 17.1 years in Japan, with a range of 3-30 years. In one study of 10 Lebanese cases, the mean age at diagnosis was 19 years.[8]

Prognosis

Confluent and reticulated papillomatosis is a chronic disease characterized by exacerbations and remissions. Discontinuation of successful therapy usually results in recurrence of the confluent and reticulated papillomatosis.

History

Patients with confluent and reticulated papillomatosis are often asymptomatic, but they may experience mild pruritus. In a study of cases in Japan, 57.1% were asymptomatic, while the rest experienced pruritus. Eight of ten were without symptoms in a Lebanese survey[19] Patients observe reticulated and pigmented macules, patches, and plaques most commonly on the chest.[8]

One expects the following, proposed as diagnostic criteria: (1) scaly brown macules and patches, with some appearing reticulated and papillomatous; (2) involvement of the upper trunk, neck, or flexural areas; (3) negative fungal staining of scales or no response to antifungal treatment; and (4) favorable response to antibiotics.[20]  Spontaneous regression may occur.[21]

Physical Examination

Physical findings of confluent and reticulated papillomatosis are limited to the skin, as shown in the images below.



View Image

Grayish brown hyperkeratotic papules and plaques in a confluent pattern on the intermammary region with a reticular pattern peripherally.



View Image

Close-up view of the interscapular area, again demonstrating a confluent pattern centrally and a more reticular pattern peripherally.

Primary lesion in confluent and reticulated papillomatosis

Lesions begin as slightly hyperkeratotic to warty papules that are 1-2 mm in diameter. They enlarge to 4-5 mm in diameter and coalesce to form a reticular pattern peripherally and confluent plaques centrally.

Skin markings are preserved and sometimes exaggerated, especially in the neck and the axillae, where the skin may be thickened. It has been described with vertically rippled and keratotic plaques[22] and as punctate pigmented papillomatosis.[23] The former have also been called linear pseudostriae and are characterized as a diagnostic sign.[24]

Atrophic macules rarely may be seen.

Scraping of lesions produces a fine powdery scale or mealy deposit.

Dermoscopic evaluation may show a brownish pigmentation with ill-defined borders, covered with white scales and a pattern of labeled "sulci and gyri".[25]

The color of confluent and reticulated papillomatosis is noteworthy; they are erythematous early and later evolve to grayish brown.

Distribution of lesions in confluent and reticulated papillomatosis

This autosomal dominant trait is characterized by many asymptomatic oval macules symmetrically distributed on axillae, groin, face, neck, arms, and trunk; scattered comedolike papules (dark dot follicles); and pitted acneiform scars.[26]

Confluent and reticulated papillomatosis usually begins on the skin of the intermammary or epigastric region, spreading over a period of weeks or months to the breasts, the lower abdomen, the flanks, and the pubic area.

In one case, lesions were entirely confined to the cheeks[27] ; in another case, lesions were entirely confined to the pubic area.[28]

The eruption may be found in the interscapular region, from which it spreads to the shoulders, the nape of the neck, and the gluteal cleft.

Involvement of the face and the proximal extremities may be seen.[29] It may also occur on the forehead.[30]

The mucous membranes are spared.

Laboratory Studies

KOH examination of skin scrapings in confluent and reticulated papillomatosis: Pityrosporum orbiculare or Pityrosporum ovale spores and rarely hyphae may be found.

Fungal culture in confluent and reticulated papillomatosis: P orbiculare or P ovale may be cultured in some cases. The laboratory needs to be informed to make specific modifications to the media to grow this yeast.

Other Tests

Wood lamp examination in confluent and reticulated papillomatosis: Yellow fluorescence occurs when Pityrosporum organisms are present.

Histologic Findings

In confluent and reticulated papillomatosis, the epidermis shows compact hyperkeratosis, often associated with the presence of Pityrosporum yeast. Other features are less consistent and include a decreased or absent granular cell layer, papillomatosis, and a stratum spinosum that varies from acanthotic to atrophic. Because papillomatosis is an inconsistent feature, one paper has proposed changing the name of confluent and reticulated papillomatosis to confluent and reticulated papulosquamous eruption. This name is also less than perfect because most patients have little-to-no scale associated with the lesions. The dermis may contain a perivascular lymphocytic infiltrate.

On electron microscopy, some lesions demonstrate an alteration in the arrangement and the structure of cornified cells, an increased transitional cell layer, an increase in the number of lamellar bodies in the stratum granulosum, and an increased number of melanosomes in the stratum corneum.[37]

Immunohistochemical analysis shows suprabasal keratin 16 expression with intense focal staining in the stratum granulosum and an increased number of epidermal cells with Ki-67 binding in the basal layer and stratum malpighii. See the image below.



View Image

A biopsy specimen showing hyperkeratosis, papillomatosis, and a mild superficial perivascular inflammation (hematoxylin and eosin, original magnificat....

Approach Considerations

Confluent and reticulated papillomatosis is strictly a disorder of the skin that results in cosmetic disfigurement, with no adverse systemic effects; therefore, no treatment is necessary other than for eradication of the rash (see Medication).

Many different modalities have been used in the treatment of confluent and reticulated papillomatosis, with variable results. The most consistent results may be seen with minocycline.[38, 39, 40, 41, 42, 43] Oral doxycycline is another option.[44] Other modalities include keratolytics; intramuscular, oral, and topical forms of vitamin A; sodium thiosulphate; ammoniated mercury; oral contraceptives; oral and topical retinoids[17, 45, 46, 47, 48] ; thyroid extract; ultraviolet light; propylene glycol; antibiotics[42, 49, 50, 51, 52, 53, 54, 55, 56] ; antimycotics; and calcipotriene.[57, 58, 59, 60]

The most consistently effective treatment for confluent and reticulated papillomatosis, and the only one evaluated by retrospective and prospective studies, has been oral antibiotics. Successful treatment of confluent and reticulated papillomatosis has been reported with topical mupirocin.[61] Another therapeutic option in confluent and reticulated papillomatosis may be tazarotene gel.[62] The treatment was well tolerated and may be an alternative to systemic retinoid therapy.

A good part of the hyperpigmentation can be removed using 70% alcohol swabbing.[34]

Surgical treatment of confluent and reticulated papillomatosis has been unsuccessful.

The lesions of confluent and reticulated papillomatosis may regress with weight reduction.

Medication Summary

The goals of pharmacotherapy in confluent and reticulated papillomatosis are to reduce morbidity and to prevent complications. Numerous agents are used.[63] The effects of the often-used antibiotics include their various anti-inflammatory or immunomodulating properties. Successful treatment with oral minocycline has been described.[34, 64] Erythromycin-resistant confluent and reticulated papillomatosis may respond to minocycline.[30] Low-dose isotretinoin may be beneficial in some patients with confluent and reticulated papillomatosis.[65, 22] Oral 13-cis-retinoic acid cleared one patient after a 20-week course.[66] Topical tacrolimus is another option.[67]  Selenium sulfide,[68] etretinate,[69, 70] and tacalcitol[71]  have been used successfully. In a severe case, methotrexate was used with success.[72]

Clotrimazole topical (Lotrimin, Anti-Fungal, Cruex)

Clinical Context:  Clotrimazole is a broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing death of fungal cells. Reevaluate the diagnosis if no clinical improvement is observed after 4 weeks. Use 1% solution.

Miconazole topical (Lotrimin AF, Fungoid, Micaderm, DermaFungal)

Clinical Context:  Miconazole damages the fungal cell wall membrane by inhibiting biosynthesis of ergosterol. Membrane permeability is increased, causing nutrients to leak out and resulting in fungal cell death. Lotion is preferred in intertriginous areas. If cream is used, apply sparingly to avoid maceration effects. Use 2% cream.

Ketoconazole (Nizoral, Extina, Xolegel)

Clinical Context:  Ketoconazole is an imidazole broad-spectrum antifungal agent; it inhibits synthesis of ergosterol, causing cellular components to leak and resulting in fungal cell death.

Class Summary

These agents are directed against Pityrosporum infection. Selenium also has keratolytic properties.

Tretinoin topical (Retin-A, Avita, Atralin, Tretin X)

Clinical Context:  Tretinoin inhibits microcomedo formation and eliminates existing lesions. It makes keratinocytes in sebaceous follicles less adherent and easier to remove. Tretinoin is available as 0.025%, 0.05%, and 0.1% creams. It is also available as 0.01% and 0.025% gels.

Isotretinoin (Amnesteem, Claravis, Myorisan, Sotret)

Clinical Context:  Isotretinoin is an oral agent that treats serious dermatologic conditions. Isotretinoin is the synthetic 13-cis isomer of the naturally occurring tretinoin (trans- retinoic acid). Both agents are structurally related to vitamin A. Isotretinoin decreases sebaceous gland size and sebum production. It may inhibit sebaceous gland differentiation and abnormal keratinization.

A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.

Tazarotene (Tazorac, Avage)

Clinical Context:  Tazarotene is a retinoid prodrug whose active metabolite modulates differentiation and proliferation of epithelial tissue; it may also have anti-inflammatory and immunomodulatory properties.

Class Summary

These agents correct disorders of keratinization.

Doxycycline (Adoxa, Alodox, Doxy 100, Bio-Tab, Doryx)

Clinical Context:  Doxycycline inhibits protein synthesis and, thus, bacterial growth, by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Minocycline (Dynacin, Minocin, Solodyn)

Clinical Context:  Minocycline treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma organisms.

Azithromycin (Zithromax, Zmax)

Clinical Context:  Azithromycin is used to treat uncomplicated skin and skin structure infections. It acts by binding to the 50S ribosomal subunit of susceptible microorganisms and blocks dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Erythromycin (E.E.S., Ery-Tab, EryPed)

Clinical Context:  Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Clarithromycin (Biaxin, Biaxin XL)

Clinical Context:  Clarithromycin is a semisynthetic macrolide antibiotic that reversibly binds to P site of the 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.

Cefdinir

Clinical Context:  Cefdinir is a third-generation cephalosporin indicated for uncomplicated skin infections.

Class Summary

These agents are antibacterials, and they may have anti-inflammatory or antiproliferative effects.

Calcipotriene (Dovonex, Sorilux, Calcitrene)

Clinical Context:  Calcipotriene is a synthetic vitamin D-3 analog that regulates skin cell production and development. Use 0.005% cream, ointment, or solution.

Selenium sulfide topical (Tersi, Dandrex, Head & Shoulders, Selsun Blue)

Clinical Context:  Selenium has keratolytic properties[58] . Blocks enzymes involved in growth of epithelial tissue.

Class Summary

Agents that inhibit enzymes involved in growth of epithelial tissue may be used. These agents correct disorders of keratinization.

What are confluent and reticulated papillomatosis?What is the pathophysiology of confluent and reticulated papillomatosis?What causes confluent and reticulated papillomatosis?What is the role of endocrine abnormalities in the etiology of confluent and reticulated papillomatosis?What is the role of keratinization in the etiology of confluent and reticulated papillomatosis?What is the role of fungal infections in the etiology of confluent and reticulated papillomatosis?What is the role of bacterial infections in the etiology of confluent and reticulated papillomatosis?What is the role of amyloidosis in the pathogenesis of confluent and reticulated papillomatosis?What is the prevalence of confluent and reticulated papillomatosis?What are the racial predilections of confluent and reticulated papillomatosis?What are the sexual predilections of confluent and reticulated papillomatosis?How does the prevalence of confluent and reticulated papillomatosis vary by age?What is the prognosis of confluent and reticulated papillomatosis?Which clinical history findings are characteristic of confluent and reticulated papillomatosis?Which physical findings are characteristic of confluent and reticulated papillomatosis?How are the primary lesions in confluent and reticulated papillomatosis characterized?Which lesion distribution patterns suggest confluent and reticulated papillomatosis?Which conditions should be included in the differential diagnoses of confluent and reticulated papillomatosis?What are the differential diagnoses for Confluent and Reticulated Papillomatosis?What is the role of lab studies in the diagnosis of confluent and reticulated papillomatosis?What is the role of a wood lamp exam in the diagnosis of confluent and reticulated papillomatosis?Which histologic findings are characteristic of confluent and reticulated papillomatosis?How is confluent and reticulated papillomatosis treated?What is the role of drug treatment for confluent and reticulated papillomatosis?Which medications in the drug class Topical Skin Products are used in the treatment of Confluent and Reticulated Papillomatosis?Which medications in the drug class Antibiotics, Other are used in the treatment of Confluent and Reticulated Papillomatosis?Which medications in the drug class Retinoid-like Agents are used in the treatment of Confluent and Reticulated Papillomatosis?Which medications in the drug class Antifungals, Other are used in the treatment of Confluent and Reticulated Papillomatosis?

Author

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Additional Contributors

Ponciano D Cruz, Jr, MD, Professor and Vice-Chair, Paul R Bergstresser Chair, Department of Dermatology, University of Texas Southwestern Medical Center

Disclosure: Received consulting fee from RCTS for independent contractor; Received honoraria from Mary Kay Cosmetics for consulting; Received grant/research funds from Galderma for principal investigator.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Kenneth A. Becker, MD, to the development and writing of this article.

References

  1. Gougerot H, Carteaud A. Papillomatose pigmentee inominee. Bull Soc Fr Dermatol Syphiligr. 1927. 34:719-21.
  2. Gougerot H, Carteaud A. Papillomatose pigmentee confluente et reticulee innominee. Bull Soc Fr Dermatol Syphiligr. 1928. 35:230-1.
  3. Gougerot H, Carteaud A. Neue formen der papillomatose. Arch Dermat Syph. 1932. 165:232-67.
  4. Wise F, Sachs, W. Cutaneous papillomatose: papillomatose confluente et reticulee. Arch Dermatol Syphil. 1937. 36:475-85.
  5. Wise F. Confluent and reticular papillomatosis (Gougerot-Carteaud). Arch Dermatol Syhphil. 1937. 35:550.
  6. Fite LP, Cohen PR. Polycystic Ovarian Syndrome-associated Confluent and Reticulated Papillomatosis: Report of a Patient Successfully Treated with Azithromycin. J Clin Aesthet Dermatol. 2017 Sep. 10 (9):30-35. [View Abstract]
  7. Kanitakis J, Zambruno G, Viac J, Thivolet J. Involucrin expression in keratinization disorders of the skin--a preliminary study. Br J Dermatol. 1987 Oct. 117(4):479-86. [View Abstract]
  8. Tamraz H, Raffoul M, Kurban M, Kibbi AG, Abbas O. Confluent and reticulated papillomatosis: clinical and histopathological study of 10 cases from Lebanon. J Eur Acad Dermatol Venereol. 2011 Nov 3. [View Abstract]
  9. Baden HP. Familial cutaneous papillomatosis. Arch Dermatol. 1965 Oct. 92(4):394-5. [View Abstract]
  10. Henning JP, de Wit RF. Familial occurrence of confluent and reticulated papillomatosis. Arch Dermatol. 1981 Dec. 117(12):809-10. [View Abstract]
  11. Inalöz HS, Patel G, Knight AG. Familial confluent and reticulated papillomatosis: a further clue to the pathogenesis. Br J Dermatol. 1999. 11(Suppl 55):66.
  12. Inalöz HS, Patel GK, Knight AG. Familial confluent and reticulated papillomatosis. Arch Dermatol. 2002 Feb. 138(2):276-7. [View Abstract]
  13. Groh V, Schnyder UW, Sigg C. Papillomatose papuleuse confluente et réticulée Gougerot-Carteaud'--a further form of skin amyloidosis?. Dermatologica. 1981. 162(2):118-23. [View Abstract]
  14. Zhang CH, Zhang C, Wu J, et al. Confluent and reticulated papillomatosis associated with hyperthyroidism. Eur J Dermatol. 2010 Nov-Dec. 20(6):833-5. [View Abstract]
  15. Vassileva S, Pramatarov K, Popova L. Ultraviolet light-induced confluent and reticulated papillomatosis. J Am Acad Dermatol. 1989 Aug. 21(2 Pt 2):413-4. [View Abstract]
  16. Ballout RA, Helou G, Maatouk I. Antiretroviral-responsive confluent and reticulated papillomatosis: a case report of an unusual association. Oxf Med Case Reports. 2019 Oct. 2019 (10):omz099. [View Abstract]
  17. Kägi MK, Trüeb R, Wüthrich B, Burg G. Confluent and reticulated papillomatosis associated with atopy. Successful treatment with topical urea and tretinoin. Br J Dermatol. 1996 Feb. 134(2):381-2. [View Abstract]
  18. Natarajan S, Milne D, Jones AL, Goodfellow M, Perry J, Koerner RJ. Dietzia strain X: a newly described Actinomycete isolated from confluent and reticulated papillomatosis. Br J Dermatol. 2005 Oct. 153(4):825-7. [View Abstract]
  19. Tamraz H, Raffoul M, Kurban M, Kibbi AG, Abbas O. Confluent and reticulated papillomatosis: clinical and histopathological study of 10 cases from Lebanon. J Eur Acad Dermatol Venereol. 2013 Jan. 27(1):e119-23. [View Abstract]
  20. Jo S, Park HS, Cho S, Yoon HS. Updated diagnosis criteria for confluent and reticulated papillomatosis: a case report. Ann Dermatol. 2014 Jun. 26(3):409-10. [View Abstract]
  21. Sakiyama T, Amagai M, Ohyama M. Chronology of confluent and reticulated papillomatosis: spontaneous regression in a case after long-term follow-up may imply transient nature of the condition. J Dermatol. 2015 Mar. 42 (3):335-6. [View Abstract]
  22. Min ZS, Tan C, Xu P, Zhu WY. Confluent and reticulated papillomatosis manifested as vertically rippled and keratotic plaques. Postepy Dermatol Alergol. 2014 Oct. 31 (5):335-7. [View Abstract]
  23. Ibekwe PU, Ukonu BA. Punctate, pigmented, and verrucous papillomatosis: a rare variant of Gougerot-Carteaud syndrome. Int J Dermatol. 2015 Sep 4. [View Abstract]
  24. Morales-Cardona CA, Tejada-Figueroa C, Méndez-Velasco DM. Confluent and Reticulated Papillomatosis With Linear Pseudo-striae: A Description of 20 Cases. Actas Dermosifiliogr. 2017 Mar 2. [View Abstract]
  25. Bernardes Filho F, Quaresma MV, Rezende FC, Kac BK, Nery JA, Azulay-Abulafia L. Confluent and reticulate papillomatosis of Gougerot-Carteaud and obesity: dermoscopic findings. An Bras Dermatol. 2014 May-Jun. 89(3):507-9. [View Abstract]
  26. Bhagwat PV, Tophakhane RS, Shashikumar BM, Noronha TM, Naidu V. Three cases of Dowling Degos disease in two families. Indian J Dermatol Venereol Leprol. 2009 Jul-Aug. 75(4):398-400. [View Abstract]
  27. Faergemann J, Fredriksson T, Nathorst-Windahl G. One case of confluent and reticulate papillomatosis (Gougerot-Carteaud). Acta Derm Venereol. 1980. 60(3):269-71. [View Abstract]
  28. Broberg A, Faergemann J. A case of confluent and reticulate papillomatosis (Gougerot-Carteaud) with an unusual location. Acta Derm Venereol. 1988. 68(2):158-60. [View Abstract]
  29. Lee D, Cho KJ, Hong SK, Seo JK, Hwang SW, Sung HS. Two cases of confluent and reticulated papillomatosis with an unusual location. Acta Derm Venereol. 2009. 89(1):84-5. [View Abstract]
  30. Kim BS, Lim HJ, Kim HY, et al. Case of minocycline-effective confluent and reticulated papillomatosis with unusual location on forehead. J Dermatol. 2009 Apr. 36(4):251-3. [View Abstract]
  31. Cordero A. [Confluent and reticular papulous Gougerot and Carteaoud's papillomatosis or acanthosis nigricans.]. Soc Ital Dermatol Sifilogr Sezioni Interprov Soc Ital Dermatol Sifilogr. 1952 Nov-Dec. 93(6):500-9. [View Abstract]
  32. Degos R, Ossipowski B. [Reticulated pigmentary dermatosis of the folds: relation to acanthosis nigricans.]. Ann Dermatol Syphiligr (Paris). 1954 Mar-Apr. 81(2):147-51. [View Abstract]
  33. Fukumoto T, Kozaru T, Sakaguchi M, Oka M. Concomitant confluent and reticulated papillomatosis and acanthosis nigricans in an obese girl with insulin resistance successfully treated with oral minocycline: Case report and published work review. J Dermatol. 2017 Mar 11. [View Abstract]
  34. Berk DR. Confluent and reticulated papillomatosis response to 70% alcohol swabbing. Arch Dermatol. 2011 Feb. 147(2):247-8. [View Abstract]
  35. Ahogo KC, Gbery PI, Bamba V, Kouassi YI, Ecra EJ, Kouassi KA, et al. Confluent and Reticulated Papillomatosis of Gougerot-Carteaud on Black Skin: Two Observations. Case Rep Dermatol Med. 2016. 2016:2507542. [View Abstract]
  36. Shevchenko A, Valdes-Rodriguez R, Hsu S, Motaparthi K. Prurigo pigmentosa: Case series and differentiation from confluent and reticulated papillomatosis. JAAD Case Rep. 2018 Jan. 4 (1):77-80. [View Abstract]
  37. Jimbow M, Talpash O, Jimbow K. Confluent and reticulated papillomatosis: clinical, light and electron microscopic studies. Int J Dermatol. 1992 Jul. 31(7):480-3. [View Abstract]
  38. Fung MA, Frieden IJ, LeBoit PE, et al. Confluent and reticulate papillomatosis: successful treatment with minocycline. Arch Dermatol. 1996 Nov. 132(11):1400-1. [View Abstract]
  39. Montemarano AD, Hengge M, Sau P, Welch M. Confluent and reticulated papillomatosis: response to minocycline. J Am Acad Dermatol. 1996 Feb. 34(2 Pt 1):253-6. [View Abstract]
  40. Poskitt L, Wilkinson JD. Clearance of confluent and reticulate papillomatosis of Gougerot and Carteaud with minocycline. Br J Dermatol. 1993 Sep. 129(3):351-3. [View Abstract]
  41. Sassolas B, Plantin P, Guillet G. Confluent and reticulated papillomatosis: treatment with minocycline. J Am Acad Dermatol. 1992 Mar. 26(3 Pt 2):501-2. [View Abstract]
  42. Yamamoto A, Okubo Y, Oshima H, Oh-i T, Koga M. Two cases of confluent and reticulate papillomatosis: successful treatments of one case with cefdinir and another with minocycline. J Dermatol. 2000 Sep. 27(9):598-603. [View Abstract]
  43. Rodriguez-Carreon AA, Arenas-Guzman R, Fonte-Avalos V, Gutierrez-Mendoza D, Vega-Memije ME, Dominguez-Cherit J. [Confluent and reticulated Gougerot-Carteaud papillomatosis: a case report of an excellent response to minocycline]. Gac Med Mex. 2008 Jan-Feb. 144(1):67-70. [View Abstract]
  44. Lee SW, Loo CH, Tan WC. Confluent and reticulated papillomatosis: Case series of 3 patients from Kedah, Malaysia and literature review. Med J Malaysia. 2018 Oct. 73 (5):338-339. [View Abstract]
  45. Hodge JA, Ray MC. Confluent and reticulated papillomatosis: response to isotretinoin. J Am Acad Dermatol. 1991 Apr. 24(4):654. [View Abstract]
  46. Lee MP, Stiller MJ, McClain SA, Shupack JL, Cohen DE. Confluent and reticulated papillomatosis: response to high-dose oral isotretinoin therapy and reassessment of epidemiologic data. J Am Acad Dermatol. 1994 Aug. 31(2 Pt 2):327-31. [View Abstract]
  47. Schwartzberg JB, Schwartzberg HA. Response of confluent and reticulate papillomatosis of Gougerot and Carteaud to topical tretinoin. Cutis. 2000 Oct. 66(4):291-3. [View Abstract]
  48. Solomon BA, Laude TA. Two patients with confluent and reticulated papillomatosis: response to oral isotretinoin and 10% lactic acid lotion. J Am Acad Dermatol. 1996 Oct. 35(4):645-6. [View Abstract]
  49. Angeli-Besson C, Koeppel MC, Jacquet P, Andrac L, Sayag J. Confluent and reticulated papillomatosis (Gougerot-Carteaud) treated with tetracyclines. Int J Dermatol. 1995 Aug. 34(8):567-9. [View Abstract]
  50. Atasoy M, Ozdemir S, Aktas A, Aliagaoglu C, Karakuzu A, Erdem T. Treatment of confluent and reticulated papillomatosis with azithromycin. J Dermatol. 2004 Aug. 31(8):682-6. [View Abstract]
  51. Carteaud A. [A case of Gougerot and Carteaud's confluent and reticulated papulous papillomatosis, completely cleared up by antibiotics]. Bull Soc Fr Dermatol Syphiligr. 1965 Jul-Aug. 72(4):396-7. [View Abstract]
  52. Gruber F, Zamolo G, Saftic M, Peharda V, Kastelan M. Treatment of confluent and reticulated papillomatosis with azithromycin. Clin Exp Dermatol. 1998 Jul. 23(4):191. [View Abstract]
  53. Jang HS, Oh CK, Cha JH, Cho SH, Kwon KS. Six cases of confluent and reticulated papillomatosis alleviated by various antibiotics. J Am Acad Dermatol. 2001 Apr. 44(4):652-5. [View Abstract]
  54. Raja Babu KK, Snehal S, Sudha Vani D. Confluent and reticulate papillomatosis: successful treatment with azithromycin. Br J Dermatol. 2000 Jun. 142(6):1252-3. [View Abstract]
  55. Weigl LB, Beham A, Schnopp C, Möhrenschlager M, Abeck D. [Confluent and reticulate papillomatosis. Successful therapy with azithromycin]. Hautarzt. 2001 Oct. 52(10 Pt 2):947-9. [View Abstract]
  56. Davis RF, Harman KE. Confluent and reticulated papillomatosis successfully treated with amoxicillin. Br J Dermatol. 2007 Mar. 156(3):583-4. [View Abstract]
  57. Bayramgurler D, Apaydin R, Bilen N. Confluent and reticulate papillomatosis: response to topical calcipotriol. J Dermatolog Treat. 2000. 11:109-11.
  58. Carrozzo AM, Gatti S, Ferranti G, Primavera G, Vidolin AP, Nini G. Calcipotriol treatment of confluent and reticulated papillomatosis (Gougerot-Carteaud syndrome). J Eur Acad Dermatol Venereol. 2000 Mar. 14(2):131-3. [View Abstract]
  59. Gulec AT, Seckin D. Confluent and reticulated papillomatosis: treatment with topical calcipotriol. Br J Dermatol. 1999 Dec. 141(6):1150-1. [View Abstract]
  60. Kurkcuoglu N, Celebi CR. Confluent and reticulated papillomatosis: response to topical calcipotriol. Dermatology. 1995. 191(4):341-2. [View Abstract]
  61. Gonul M, Cakmak SK, Soylu S, Kilic A, Gul U, Ergul G. Successful treatment of confluent and reticulated papillomatosis with topical mupirocin. J Eur Acad Dermatol Venereol. 2008 Sep. 22(9):1140-2. [View Abstract]
  62. Bowman PH, Davis LS. Confluent and reticulated papillomatosis: response to tazarotene. J Am Acad Dermatol. 2003 May. 48(5 Suppl):S80-1. [View Abstract]
  63. Ferreira LM, Diniz LM, Ferreira CJ. [Confluent and reticulated papillomatosis of Gougerot and Carteaud: report of three cases]. An Bras Dermatol. 2009 Jan-Feb. 84(1):78-81. [View Abstract]
  64. Rao TN, Guruprasad P, Sowjanya ChL, Nagasridevi I. Confluent and reticulated papillomatosis: successful treatment with minocycline. Indian J Dermatol Venereol Leprol. 2010 Nov-Dec. 76(6):725. [View Abstract]
  65. Erkek E, Ayva S, Atasoy P, Emeksiz MC. Confluent and reticulated papillomatosis: favourable response to low-dose isotretinoin. J Eur Acad Dermatol Venereol. 2009 Nov. 23(11):1342-3. [View Abstract]
  66. Carlin N, Marcus L, Carlin R. Gougerot-Carteaud Syndrome Treated with 13-cis-retinoic Acid. J Clin Aesthet Dermatol. 2010 Jul. 3(7):56-7. [View Abstract]
  67. Tirado-Sánchez A, Ponce-Olivera RM. Tacrolimus in confluent and reticulated papillomatosis of Gougerot Carteaud. Int J Dermatol. 2013 Apr. 52(4):513-4. [View Abstract]
  68. Nordby CA, Mitchell AJ. Confluent and reticulated papillomatosis responsive to selenium sulfide. Int J Dermatol. 1986 Apr. 25(3):194-9. [View Abstract]
  69. Baalbaki SA, Malak JA, al-Khars MA. Confluent and reticulated papillomatosis. Treatment with etretinate. Arch Dermatol. 1993 Aug. 129(8):961-3. [View Abstract]
  70. Bruynzeel-Koomen CA, de Wit RF. Confluent and reticulated papillomatosis successfully treated with the aromatic etretinate. Arch Dermatol. 1984 Sep. 120(9):1236-7. [View Abstract]
  71. Ginarte M, Fabeiro JM, Toribio J. Confluent and reticulated papillomatosis (Gougerot-Carteaud) successfully treated with tacalcitol. J Dermatolog Treat. 2002 Mar. 13(1):27-30. [View Abstract]
  72. Nunes de Mattos AB, Brummer CF, Funchal GDG, Nunes DH. Use of methotrexate in an exuberant case of confluent and reticulated papillomatosis of Gougerot and Carteaud in a teenager. An Bras Dermatol. 2019 Nov - Dec. 94 (6):717-720. [View Abstract]

Grayish brown hyperkeratotic papules and plaques in a confluent pattern on the intermammary region with a reticular pattern peripherally.

Close-up view of the interscapular area, again demonstrating a confluent pattern centrally and a more reticular pattern peripherally.

A biopsy specimen showing hyperkeratosis, papillomatosis, and a mild superficial perivascular inflammation (hematoxylin and eosin, original magnification X125).

Grayish brown hyperkeratotic papules and plaques in a confluent pattern on the intermammary region with a reticular pattern peripherally.

Close-up view of the interscapular area, again demonstrating a confluent pattern centrally and a more reticular pattern peripherally.

A biopsy specimen showing hyperkeratosis, papillomatosis, and a mild superficial perivascular inflammation (hematoxylin and eosin, original magnification X125).