Inflammatory Diseases of Hair Follicles, Sweat Glands, and Cartilage Dr Mehrolhasani

Acne vulgaris The development of a comedone involves infundibular dilation and thinning of the follicular wall. A plug composed of Ioosely arranged keratinized cells and sebum forms . Sebum is made up of sebaceous lipids and microorganisms.

In closed comedones, the follicular orifice remains more or less normal in size, but when the follicular ostium widens,an open comedone results. Attenuation of the follicular wall may be so extreme as to lead to rupture .

Release of follicular contents into the dermis generates an inflammatory response initially mediated by neutrophils and later by histiocytes and foreign-body giant cells. it tends to lead to the development of a clinical pustule, but when it occurs in the deeper dermis, an inflammatory nodule forms . If the follicular damage and inflammatory response are severe, scarring can result. in severe forms of acne (cystic acne and acne fulminans), extensive inflammation can result in dermal necrosis with large abscesses.

Stroid acne Acne due to both topical and systemic corticosteroids shows similar histologic features. Despite the apparent absence of comedones clinically, histologic features resembled those of acne vulgaris ,albeit with an accelerated rate of development . biopsied flesh-colored papules that measured 1mm showed infundibular spongiosis, hyperkeratosis, perifollicular edema, microcomedo formation, and infundibular wall thinning, sometimes with infundibular rupture. Biopsied lesions that were 2 mm or greater and clinically inflamed frequently showed infundibular rupture, necrotic keratinocytes, and surrounding suppurative and granulomatous inflammation that included multinucleated giant cells amid keratinous debris.

Perioral dermatitis Some authors consider perioral dermatitis to be a variant of rosacea, with indistinguishable histologic features , whereas others consider the two entities to be distinct , with some histologic overlap. Fully developed lesions show spongiosis of the follicular infundibulum with mild mononuclear cell exocytosis . The epidermis may show mild acanthosis and parakeratosis, particularly about follicular ostia. The perifollicular dermis shows Iymphohistiocytic inflammation around vessels. Lesions tend to lack the dermal edema and telangiectasias characterist of rosacea .

Lesions of childhood granuLomatous periorificiaL dermatitis often resemble granulomatous rosacea, with noncaseating perifollicular granulomas with some giant cells. Other features include epidermal changes consisting of mild hyperkeratosis and spongiosis, as well as dermal inflammation, composed of lymphocytes and histiocytes, that is mild to moderate, perivascular, and perifollicular.

rosacea Vascular dilation of upper and middermal vessels with perivascular and perifollicular lymphohistiocytic inflammation (and occasional plasma cells) is generally present in all cases . Lymphatic dilation is also common . With mild follicular involvement, there is infundibular spongiosis and lymphocyte exocytosis. With more extensive follicular involvement, neutrophils accumulate, resulting in a superficial pustule.

Granulomatous infiltrates are reported to occur in about 10% of all cases of rosacea, and caseation necrosis has been identified in about 10% of these patients . Granulomatous rosacea can histologically mimic mycobacrerial infections, with epithelioid histiocytes forming a tuberculoid pattern. In such cases, tissue cultures, may be necessary. Less frequenrly, the changes resemble cutaneous sarcoidosis. Multinucleated giant cells of the foreign body type may aggregare around follicular.

In a study of rhinophyma, the classic or common type showed histologic fearures of fully developed rosacea, except for sebaceous gland hyperplasia, which can be prominent . in patients with the severe form of rhinophyma, there is marked dermal thickening with sclerotic collagen bundles and large amounts of mucin, an absence of pilosebaceous structures, sparse inflammation, and telangiectasias. Many spindle-shaped and "bizarre" cells staining for factor XIIIa were seen in the intrerstitum. It was noted that the microscopic findings in the severe form of rhinophyma demonestrate many similarities to elephantiasis nostras caused by chronic lower-extremiry lymphedema.

Demodicidosis The diagnosis can be made in the clinical setting by examining scale with 40% KOH or by standardized skin surface biopsy (SSSB), in which cyanoacrylate glue is used to sample the horny layer and follicular contents . The presence of five or more mites in a single low-power field by KOH or more than 5/cm2 by SSSB is considered significant.

Biopsies of pityriasis folliculorum show a perivascular and diffuse dermal lymphocytic infiltrate without granuloma formation . Demodex mites are present within pilosebaceous units. Biopsies of rosacea-like demodicidosis show a primarily perifollicular infiltrate of mononuclear cells with possible granulomatous inflammation. The infiltrate is composed predominantly of CD4+ T lymphocytes , and perifollicular Langerhans cells may be found. "Demodicidosis gravis" shows granulomas with central necrosis (caseation) and foreign-body-type multinucleated giant cells .

Lupus Miliaris Disseminatus Faciei Biopsy specimens sectioned through the central portion of a papular lesion demonstrate one of the most highly characteristic patterns of cutaneous histopathology. Surrounding a usually large area of caseous necrosis, aggregates of epithelioid histiocytes and occasional multinucleate giant cells form a "tubercle" with sparse lymphoid inflammation at the periphery .

Despite the histologic picture, no direct relationship with tuberculosis has been documented, including testing using polymerase chain reaction with DNA fragments specific for Mycobacterium tuberculosis complex .

Eosinophilic Pustular Folliculitis In Ofuji's disease, there is exocytosis of eosinophils into a spongiotic follicular infundibulum and accompanying sebaceous gland, eventually forming eosinophilic micropustules . epidermis adjacent to the affected follicle may contain lymphocytes and eosinophils, with the latter aggregating into small eosinophilic pustules that are subcorneal or intraepidermal; these epidermal changes reflect the histologic picture seen in palmoplantar lesions, where follicles are absent. In the dermis, there are perivascular and interstitial infiltrates of lymphocytes and numerous eosinophils, which may surround sweat glands.

HIV-associated eosinophilic folliculitis: Perifollicular and intrafollicular lymphocytes and eosinophils are concentrated about the isthmus, and may involve the sebaceous duct. There is spongiosis of the follicular epithelium. Eosinophils and lymphocytes may be seen aggregating in the hair canal, but neutrophils are rare. Dense eosinophilic infiltration with degranulation and flame figures, resembling Well's syndrome, may sometimes be seen. Bacteria, yeast, or Demodex may be identified, albeit away from the areas of inflammation. excoriation is a common secondary finding.

suppurative folliculitis in HIV-positive patients more commonly shows an infiltrate dominated by neutrophils and macrophages, the presence of microorganisms amid the inflammation, and rupture of the involved follicle.

Follicular Mucinosis and Alopecia Mucinosa Within the outer root sheath and sebaceous gland epithelium, there is reticular epithelial degeneration that sometimes evolves into more extensive cavitation within which mucin is deposited . Occasionally, little mucin can be detected, perhaps because of removal of this water-soluble material in the processing procedure. The deposited mucin is an acid mucopolysaccharide that stains metachromatically with toluidine blue at pH 3.0, as well as with Alcian blue at acid pH. the mucin is predominantly hyaluronic acid. Colloidal iron stain may also be used for its detection.

features that have favoring a lymphoma-associated lesion include an atypical lymphocytic infiltrate or increased density of the perifollicular infiltrate with substantial foliculotropism a study also suggested that substantial follt a prominent eosinophilic infiltrate and more substantial mucin deposition tend to favor a benign process, but a subsequent study failed to substantiate these findings .

Keratosis Pilaris An orthokeratotic keratin plug blocks and dilates the orifice and upper portion of the follicular infundibulum A twisted hair shaft may be trapped within this keratin material, and mild perivasculat mononuclear cell infiltrates are usually present in the adjacent dermis. A similar condition, lichen spinulosus shows a very similar histologic picture except that the keratin plug may protrude more substantially above the skin surface and contain one or more hair shafts . Lesions similar to keratosis pilaris may also be seen in phrynoderma , but the follicular keratin plug is said to be parakeratotic .

Trichostasis Spinulosa Affected hair follicles demonstrate retention of small hair shafts within a dilated infundibulum, sometimes enveloped in a keratinous sheath. A perifollicular mononuclear infiltrate may be present.

Alopecia Areata The diagnostic pathologic feature is peribulbar lymphocytic inflammation ("swarm of bees") affecting anagen follicles or follicles in early catagen. The inflammatory assault on anagen follicles induces a premature conversion to catagen . Consequently, the number of catagen and telogen follicles found may be marked,approaching 100% . Telogen hairs show little to no perifollicular inflammation.

As a result of injury to bulbar melanocytes and keratinocytes, pigment casts, which are clumps of melanin pigment may seen. Pigment casts are more often found in trichotillomania; Pigment casts have also been found in postoperative pressure-induced alopecia, to postulate that they resulted from the sudden conversion of follicles from anagen to catagen, as occurs in trichotillomania and AA .

The inflammatory assault may produce dysmorphic follicles and shafts The inflammatory assault may produce dysmorphic follicles and shafts. (termed trichomalacia). The hair shaft may taper to a point so tiny and fragile that it fractures. Small, abnormal follicles called nanogen hairs are a distinctive finding in longstanding cases.they show only a minute, incompletely keratinized hair shaft or no shaft At all.

anagen duration becomes shorter and shorter and the follicles begin to miniaturize . As the follicles decrease in size they become situated more superficially, with their bulbs situated in the mid to lower dermis .

transversely sectioned scalp biopsies showed the diagnostic features of alopecia areata more often than vertically sectioned biopsies . Follicular density can decrease in severe alopecia totalis and universalis of long duration (a decade or more), with scars replacing some of the follicular sheaths .

use of follicular counts to aid in the diagnosis of AA when the characteristic peribulbar inflammation is missing, with a high percentage of catagen or telogen hairs and miniaturized hairs as a strong sign of AA . The presence of eosinophils around the bulb and within fibrous tracts was found to be a helpful diagnostic feature .

Trichotillomania In horizontally sectioned biopsies of trichotillomania uncomplicated by the coexistence of other types of alopecia, the density of hair follicles is normal, as is the terminal-to-vellus hair ratio. The diagnostic finding, when seen, is distorted hair follicle anatomy, without inflammation the pulling of hairs can leave behind empty anagen follicles and "torn-away" follicles, the result of plucked hair shafts that retain parts of the hair matrix and root sheaths . Additional microscopic evidence of traumatic injury was the "hamburger sign," describing a vertically oriented split in the hair shaft containing proteinaceous material and erythrocytes, resembling a hamburger within a bun . Damaged follicles enter the resting phase, leading to an increase in the percentage of catagen and telogen hairs.

Pigment casts, which are clumps of melanin pigment, may be seen in the hair papilla and peribulbar connective tissue. They are also commonly seen . Pigment casts are due to injury to the hair matrix, although some authors have theorized that they result from the sudden conversion of anagen to catagen . Hair shaft changes, termed trichomalacia, may be seen. Characterized by diminished size, distorted and odd shape, and irregular pigmentation of the shaft.

Because not all follicles in a given area are affected, transversely sectioned scalp biopsies may increase the yield of finding the diagnostic histologic features of trichotillomania.

Traction alopecia In early traction alopecia, the histologic findings are similar to those of trichotillomania, albeit more subtle. In late disease, permanent loss of terminal follicles occurs with replacement of follicular tracts by scar tissue. Because velIus hairs are not sufficiently large to be included in the method of styling and be affected by tractional forces, these hairs are preserved, and this is reflected in a normal absolute number of vellus follicles, often outnumbering terminal follicles. In late disease, the pathology shows an "end-stage" scarring alopecia.

Anagen Effluvium Diagnosis of anagen effluvium is usually made on clinical grounds with the aid of a trichogram or gentle hair pull, so that scalp biopsies are seldom done. Resting (telogen) hairs are immune to the metabolic insult, so that when sufficient anagen hairs are lost through shedding, a forcible hair pluck performed late in the course of disease will show almost all telogen hairs; Early, a gentle hair pull demonstrates "pencil-point" tapered hairs with a pointed or frayed end .

Telogen Effluvium There is a normal number of hair follicles and an absence of follicular miniaturization, unless telogen effluvium occurs in patients with established androgenetic or another form of involutional alopecia. Inflammation is generally not seen. Telogen follicles, characterized histologically by trichilemmal keratinization of the most proximal portion of the hair shaft, are increased.

Telogen follicles in excess of 15% are considered to be abnormal and suggest a diagnosis of telogen effluvium in the absence of significant inflammation and miniaturization. Others have suggested that a level of 25% is necessary for a definitive diagnosis of telogen effluvium .

Androgenetic Alopecia Satisfactory evaluation of AGA can only be achieved from transverse sectioning of punch biopsy material, allowing for quantitative evaluation. samples smaller than 4 mm in diameter show an insufficient number of follicles for meaningful results. Diminution of follicular size, or miniaturization, is the hallmark of AGA. To fully appreciate the number of miniaturized follicles, horizontal sections at the level of the lower infundibulum of terminal hair follicles should be examined because sections below this may miss the vellus hairs whose bulbs are situated in the upper dermis .

In advanced AGA there may be a reduced hair density with permanent loss of follicles, termed cicatricial pattern hair loss. In subtle cases, a second biopsy, taken from the occipital scalp, may be helpful for comparison because the occiput is typically uninvolved.

The presence of inflammation has been reported in as many as 50% to 75% of cases and has been linked to peripilar signs seen clinically . However, mild perifollicular and upper dermal inflammation can be observed in normal scalp with a similar frequency to AGA and therefore is of no value in diagnosing AGA .

Nevertheless, its presence may have a bearing on the potential to respond to treatment; one study found that AGA patients with histologic inflammation or fibrosis showed less frequent regrowth on treatment with 2% minoxidil than AGA patients without inflammation

Pseudopelade of Brocq Because the histologic findings of a typical lesion of PPB are those of a "burnt-out" scarring alopecia , clinical correlation is always necessary for accurate interpretation. The classic description of PPB is one of predominantly follicular scarring characterized by columns of fibrosis replacing hair follicles , sometimes extending into the subcutaneous fat. This is accompanied by a loss or decrease of sebaceous glands . Normal arrector pili muscles remain. The epidermis may be normal or, rarely, atrophic, and sweat glands are normal. Marked inflammation is absent.

Direct immuno fluorescence in PPB is negative, with occasional immunoglobulin M at the basement membrane zone of the follicular infundibulum . Immunofluorescence changes of lupus erythematosus and lichen planopilaris should be absent .

Central Centrifugal Cicatricial Alopecia The earliest and most characteristic histologic finding of CCCA is premature desquamation of the inner root sheath , typically seen in only a few follicles. The inner root sheath normally degenerates at the isthmus, which is delimited below by the attachment point of the arrector pili muscle and above by the insertion of the sebaceous duct. "Crumbling" or absence of the inner root sheath below the isthmus, at a level through the deep dermis near the eccrine coils or in the subcutis, characterizes this finding.

premature desquamation of the inner root sheath could also be seen in chronic cutaneous lupus erythematosus and pseudopelade of Brocq . What is unique to CCCA, however, is its occurrence early in the disease process.

Tufted Hair Folliculitis Histology shows a single group of three to five follicles, in which the infundibular epithelium of the affected hair follicles is fused together so that the multiple hair shafts are situated in the infundibular hair canal and exit the skin through a shared ostium. The lower segments of the hairs are unaffected. The epidermis may be depressed from contraction of the fibrous tissue, forming a dell from which the hairs emerge.

Postmenopausal Frontal Fibrosing Alopecia Biopsies show histologic features of lichen planopilaris , including perifollicular lymphocytic inflammation affecting the lower infundibulum and isthmus area near the bulge, hydropic degeneration of basal follicular keratinocytes with necrotic cells, concentric fibroplasia around the upper follicle, and absence of interfollicular changes. Naked hair shafts surrounded by granulomatous inflammation may be seen. Late lesions resemble burnt out scarring alopecia.

Lipedematous Alopecia The defining abnormality is increased thickness of the subcutaneous fat layer . To appreciate this on biopsy, the specimen must extend to the galea, and vertical sections are required. There is no evidence of adipose tissue hypertrophy or hyperplasia; instead, there is edema. Excess mucin deposition is not generally characteristic but was seen in some cases.

Neutrophilic Eccrine Hidradenitis The histology of palmoplantar hidradenitis occurring in children is similar to that of NEH induced by certain forms of chemotherapy , except that syringosquamous metaplasia is missing . A neutrophilic infiltrate is centered on the eccrine gland coils . There may be mild mixed inflammation surrounding vessels in the mid and deep dermis, without leukocytoclastic vasculitis.

Fox-Fordyce Disease Step sections of a vertically oriented biopsy specimen are usually needed. There is hyperkeratosis of the follicular infundibulum and excretory duct of the apocrine sweat gland at the point where the latter inserts into the hair follicle. The apocrine duct behind the obstructing keratin plug becomes dilated.

other possible microscopic findings, including vacuolar alteration at the dermoepithelial junction of infundibula, dyskeratotic cells in infundibula, cornoid lamella-like parakeratosis within an orthokeratotic plug filling a dilated infundibulum, and foamy macro phages surrounding follicular infundibula and apocrine ducts.

Chondrodermatitis Nodularis Helicis Epidermal ulceration or a wedge-shaped epidermal defect is usually present. The intact adjacent epidermis is hyperplastic . The dermis directly below shows fibrinoid collagen degeneration that stains more deeply eosinophilic than reticular dermal collagen, is homogeneous, and is acellular . The stroma adjacent to the zone of degeneration shows vascular proliferation with lymphohistiocytic inflammatory cells. Glomus cell aggregates have been described in these vascularized granulation tissue-like areas . Peripheral solar elastosis is common.

The underlying perichondrial tissue may be thickened and The underlying perichondrial tissue may be thickened and . Degeneration of underlying cartilage with loss of cell nuclei can occur, although it is usually minimal. If cartilaginous degeneration is severe, there may be focal calcification and ossification. Nerve hyperplasia was found , potentially explaining the tenderness of lesions.

Relapsing Polychondritis In early cartilaginous lesions, only the marginal chondrocytes appear degenerate, showing vacuolization,nuclear pyknosis, and loss of basophilia, which has been shown to result from the release of chondroitin sulfate from the cartilage matrix . A dense inflammatory infiltrate develops in the perichondrium, which comprises neutrophils, lymphocytes, eosinophils, plasma cells, and macrophages. There may be fragmentation of the cartilage with necrosis and lysis of the cartilaginous plates . Elastic tissue stain shows clumping and destruction of cartilaginous elastic fibers . With successive episodes,fibrosis ensues.

Pseudocyst of the Auricle A small intracartilaginous cavity without an epithelial lining is found on histologic examination. The wall of the pseudocyst consists of auricular cartilage, which is partially degenerated, appearing as faintly eosinophilic amorphous material . The overlying epidermis, reticular dermis, and perichondrium are all normal .