Perforating disorders are characterized by transepidermal elimination of altered keratin or dermal connective tissue material. These disorders include perforating folliculitis (as shown below), Kyrle disease, elastosis perforans serpiginosa, reactive perforating collagenosis, and acquired perforating dermatosis. Cases of overlap are described, and diagnostic criteria are not well-defined for all the entities.[1] Clinically, the lesions are hyperkeratotic to verrucous papules and nodules.
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Typical appearance of lesions of perforating folliculitis consisting of keratotic follicular papules.
In perforating folliculitis, keratotic follicular papules develop, particularly over extensor surfaces. Microscopically, the disorder is characterized by disruption of the infundibular portion of the follicular wall, with transepidermal (transfollicular) elimination of connective-tissue elements and cellular debris.
Perforating folliculitis may present as an isolated finding, apparently unrelated to other disease states, but also can be associated with chronic renal failure and diabetes mellitus. Perforating folliculitis is closely related, if not identical, to the acquired perforating dermatosis that occurs with chronic renal disease. Kyrle disease (hyperkeratosis follicularis et parafollicularis in cutem penetrans) may simply represent an exaggerated form of perforating folliculitis. In addition, another disorder of transepidermal elimination, elastosis perforans serpiginosa, occasionally displays involvement of follicular units.
As in Kyrle disease, the concept of an extrinsic keratin plug penetrating the epidermis generally has been discredited. Abnormally premature keratinization at the expense of proliferation is a possible explanation, as proposed by Carter and Constantine and Tappeiner et al in Kyrle disease.[2, 3] A role for fibronectin has been postulated. In addition, a primary alteration of connective tissue or deposition of foreign material within the superficial dermis, with subsequent engulfment and elimination by proliferative follicular epithelium, also is conceivable as a mechanism. Such a response to experimental implantation of foreign material has been described.
In addition, evidence suggests a pathologic role for excessively coiled hairs. Mehregan first proposed that curled hairs within follicular canals may act as springs, penetrating the lateral follicular wall, thereby initiating the process of transepidermal elimination.[4] Support for this concept has been provided by an ultrastructural study of acquired perforating dermatosis that showed hair shaft fragments within transepidermal channels, even in patients in whom follicular involvement was not demonstrable on routine light microscopy. Factors that may promote coiling of hairs include follicular hyperkeratosis (occasional perforated follicles can be identified in keratosis pilaris) or contact dermatitis (eg, resulting from formaldehyde in clothing). Finally, trauma, such as scratching of pruritic skin, may well play a significant role in lesional development, possibly by setting in motion one or more of the pathologic events described above.[5]
A number of reported cases of perforating folliculitis appear to be idiopathic, but specific associations also have been observed. Although some associations could be coincidental, the association with chronic renal failure (including both dialysis-dependent and nondialysis patients) is relatively common, suggesting a pathogenetic link.[6, 7, 8, 9, 10, 11] Perforating folliculitis also is observed relatively commonly in association with diabetes mellitus.
Less common associations include sclerosing cholangitis,[12, 13] hypertension, atherosclerotic cardiovascular disease, acanthosis nigricans, psoriasis,[14] and phrynoderma.[15] A single case report described an association with Poland syndrome (unilateral absence of the pectoralis major muscle and ipsilateral symbrachydactyly), but this patient also had diabetes mellitus, hyperuricemia, and dilated cardiomyopathy.[16] A single case highlighted the presence of perforating folliculitis in a patient with human immunodeficiency virus infection.[17] A case of perforating folliculitis was also reported in a child with cystic fibrosis.[18] One case of perforating folliculitis arising in a patient with preexisting antisynthetase syndrome has been reported.[19]
Drug-induced cases include associations with infliximab and etanercept as possible inciting agents in a patient with rheumatoid arthritis[20] and dose-dependent association of sorafenib with skin lesions of perforating folliculitis.[21, 22, 23, 24, 25, 26] A report of a relationship with nilotinib suggests that drugs that inhibit c-kit and PDGF-R affect normal hair follicle development. PDGF-R has been previously linked in murine and human in vitro models to affect the hair follicle cycle.[27] A case of bendamustine-rituximab chemotherapy-induced perforating folliculitis was reported in 2017.[28]
Incidence of perforating folliculitis worldwide is not known precisely, although the disorder is not uncommon. In Detroit, Michigan, 50 cases were reported during a 2-year period in the early 1970s, although this observation was followed by a declining incidence of new cases.
Race
Although generally no ethnic predilection has been identified, 1 study found a higher incidence of Kyrle disease in chronic renal failure among African American individuals.
Sex
Perforating folliculitis occurs equally in males and females; no sex predilection has been reported.
Age
Perforating folliculitis is more common in the second through fourth decades of life.
Perforating folliculitis morbidity is associated with the cosmetic appearance of lesions and the pruritus that occasionally accompanies them. Although cutaneous disease is insignificant, substantial morbidity or mortality rates can be seen in association with the primary underlying diseases, such as diabetes mellitus or chronic renal failure.
Skin lesions can improve or clear, either spontaneously or with therapy. Further therapeutic experience may permit the development of specific treatment guidelines.
Reports of improvement of perforating folliculitis lesions with stabilization of renal damage (in patients with chronic renal failure) are encouraging and underscore the important role of internal medicine or surgery consultants in treating these patients.
Inform perforating folliculitis patients about the nature of the disease and its relation to any underlying medical condition that may be present.
Instruct perforating folliculitis patients to avoid rubbing or scratching the lesions, since this may result in their spread or in the development of secondary infection.
Fully inform patients about the treatment being used, including its proper use or application and possible adverse effects.
In perforating folliculitis, papules typically are concentrated on hair-bearing portions of the extremities (arms, thighs) and buttocks. Often, lesions are asymptomatic, although pruritus may be a striking feature, especially in patients with renal insufficiency. Lesions may wax and wane and persist for months or years. Spontaneous remission can occur, and remission following renal transplantation has been documented in 1 patient who developed lesions secondary to renal failure.
Typical primary lesions of perforating folliculitis consist of 2-8 mm diameter scaly folliculocentric papules with small central keratotic plugs and varying degrees of erythema (see the image below).
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Typical appearance of lesions of perforating folliculitis consisting of keratotic follicular papules.
Compression of papules may yield keratin debris and a coiled hair or hair fragments. An initial eruption of follicular pustules, followed by typical plugged papules and subsequent development of prurigo-nodularis–like lesions was reported in 1 study. The Köebner phenomenon usually is not readily demonstrable, but a linear configuration occasionally can be observed. A case of progressive generalized perforating folliculitis has been reported to be associated with erythroderma, keratoderma of the palms and soles, alopecia of the scalp and eyebrows, and nail changes. Accompanying jaundice has been observed in patients with underlying liver disease.[29]
Potential complications of perforating folliculitis include secondary infection of lesions (resulting from trauma or other factors), spread of lesions despite therapy, or adverse effects of treatments, such as irritation from topical retinoids or atrophy and telangiectasia from chronic topical corticosteroid use.
Perforating folliculitis complications related to any underlying medical conditions may occur.
In perforating folliculitis, perform renal function studies, including urinalysis, serum creatinine, and creatinine clearance, to evaluate for possible underlying renal disease, if warranted by history and/or physical findings.
Test blood glucose levels to evaluate for possible diabetes mellitus.
Biopsy is indicated when uncertainty about the nature of an eruption exists, ie, whether or not it is a folliculitis. In particular, consultants in other specialties, such as nephrologists who are following patients for chronic renal failure, may wish to exclude vasculitis, an infectious process, or a drug eruption. Biopsy also helps distinguish perforating folliculitis from other inflammatory disorders of the hair follicle, such as irritant folliculitis, acneiform folliculitis, or infectious folliculitis (eg staphylococcal, Pseudomonas- induced, or Pityrosporum- induced folliculitis).
Since histopathologic findings in perforating folliculitis are focal, they can be missed if a skin biopsy is sectioned incompletely. As a result, a pathology report may be returned with a nonspecific diagnosis. To avoid this, a small punch biopsy that completely encompasses the lesion is recommended. The clinician should indicate on the accession form that perforating folliculitis is suspected and that multiple sections may be necessary to demonstrate diagnostic changes.
The involved hair follicle in perforating folliculitis shows focal disruption of its lateral wall, with a transepithelial channel and, often, a parakeratotic luminal plug. Connective-tissue elements, including collagen and elastin, and varying numbers of inflammatory cells can be found within this transfollicular channel and within the follicular lumen, admixed with parakeratotic keratin. In some cases, a hair shaft or hair fragment can be demonstrated within the follicular lumen and/or within the transfollicular channel. The dermis surrounding the follicle typically shows sparse inflammation and focal fibrosis.
Since some cases of perforating folliculitis are associated with systemic disorders (eg, diabetes mellitus, chronic renal failure), direct therapeutic efforts towards the underlying condition in these patients. In a case report of perforating folliculitis in a patient with diabetes mellitus and phrynoderma, the skin lesions resolved with correction of the vitamin A deficiency. Soothing antipruritic lotions may be helpful for patients in whom itching is a significant problem. UV-B irradiation also may be of general benefit in the control or amelioration of pruritus.[30]
Assessing treatments for perforating folliculitis is difficult. Although the condition is not uncommon, controlled therapeutic studies are not available. Unsuccessful treatments have included oral beta-carotene, keratolytics, antiacne therapies, and topical corticosteroids. A case of perforating folliculitis reported by Zachariae and Sogaard featured progressive generalized perforating folliculitis combined with erythroderma, keratoderma, and alopecia and was resistant to corticosteroids, corticotropin, psoralen plus UV-A, cytostatic agents, and aromatic retinoids.[31] A case of phrynoderma with perforating folliculitis reported by Neill et al responded to 50,000 U/d of beta-carotene for 1 month, followed by 2000 U/d.[15] Hurwitz found that a combination of antistaphylococcal therapy, phototherapy, and a topical corticosteroid lotion was helpful in controlling perforating folliculitis in patients with chronic renal failure.[6]
Tretinoin 0.1% cream has cleared some perforating folliculitis lesions but has not prevented the development of others. A case of successful treatment using 13-cis -retinoic acid has been reported.[32]
A 2004 study of 5 perforating folliculitis patients showed good clinical responses with narrowband UV-B therapy. Patients were treated 2-3 times weekly. The initial dose was 400 mJ/cm2, with increases to a maximum of 1500 mJ/cm2. Lesions completely resolved after 10-15 exposures, although some recurrences were observed.[30]
Practitioners may wish to consult a dermatologist when uncertainty regarding a papular eruption exists in a patient. Dermatologists often are able to determine clinically whether such an eruption is likely to be a folliculitis, and they can appreciate subtle lesional changes that suggest a perforating folliculitis. Dermatologists also can suggest or perform the proper type of biopsy procedure for this type of folliculitis.
Internist
Specialists in internal medicine should be consulted for management of patients in whom perforating folliculitis may be associated with an underlying medical condition, such as chronic renal failure, diabetes mellitus, or atherosclerotic cardiovascular disease.
General surgeon
Consultation with a surgeon may be indicated for patients whose perforating folliculitis is associated with chronic renal failure. Renal transplantation may be an option.[7]
Further outpatient dermatologic care may be required for ongoing management of the perforating folliculitis when lesions persist, spread, or become resistant to therapy.
Follow-up care may be necessary for complications related to therapy.
Outpatient internal medicine care may be indicated for management of any underlying medical conditions, such as chronic renal failure, hypertension, diabetes mellitus, or atherosclerotic cardiovascular disease.
The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications. Studies have found that a combination of antistaphylococcal therapy and a topical corticosteroid lotion may help in controlling perforating folliculitis in patients with chronic renal failure.
Clinical Context:
Clindamycin is a lincosamide for the treatment of serious skin and soft-tissue staphylococcal infections. It is effective against aerobic and anaerobic streptococci (except enterococci). It inhibits bacterial growth, possibly by blocking the dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Clinical Context:
Meropenem is a bactericidal broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis. It is effective against most gram-positive and gram-negative bacteria. It has slightly increased activity against gram-negatives and slightly decreased activity against staphylococci and streptococci compared with imipenem.
Clinical Context:
Tigecycline is a glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. It inhibits bacterial protein translation by binding to the 30S ribosomal subunit, and it blocks entry of amino-acyl tRNA molecules in the ribosome A site.
Clinical Context:
Tetracycline inhibits bacterial protein synthesis by binding with the 30S and, possibly, 50S ribosomal subunit(s). Tetracycline has anti-inflammatory activity. Administer at 250-500 mg PO bid.
Clinical Context:
Doxycycline is a broad-spectrum antibiotic with excellent gram-positive coverage, including most resistant staphylococcal organisms. It inhibits protein synthesis and, thus, bacterial growth, by binding to the 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block the dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Clinical Context:
Hydrocortisone topical is a moderate-potency adrenocorticosteroid derivative suitable for application to skin or external mucous membranes. It has mineralocorticoid and glucocorticoid effects, resulting in anti-inflammatory activity.
Clinical Context:
Fluticasone is a high-potency topical corticosteroid that inhibits cell proliferation. It is immunosuppressive and anti-inflammatory.
Topical corticosteroid lotions have proven helpful in controlling the generalized pruritus and the evolution of the lesions in patients with perforating folliculitis.
Suguru Imaeda, MD, Chief of Dermatology, Yale University Health Services; Chief of Dermatology, Veterans Affairs Connecticut Healthcare System; Assistant Professor, Department of Dermatology, Yale University School of Medicine
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.
Rosalie Elenitsas, MD, Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System
Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.
Chief Editor
Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine
Disclosure: Nothing to disclose.
Additional Contributors
Andrea Leigh Zaenglein, MD, Professor of Dermatology and Pediatrics, Department of Dermatology, Hershey Medical Center, Pennsylvania State University College of Medicine
Disclosure: Received consulting fee from Galderma for consulting; Received consulting fee from Valeant for consulting; Received consulting fee from Promius for consulting; Received consulting fee from Anacor for consulting; Received grant/research funds from Stiefel for investigator; Received grant/research funds from Astellas for investigator; Received grant/research funds from Ranbaxy for other; Received consulting fee from Ranbaxy for consulting.
Acknowledgements
The authors and editors of Medscape Reference gratefully acknowledge the significant contributions of previous author, James W. Patterson, MD, to the development and writing of this article which has been recently updated.
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