Acneiform lesions are encountered in different chapters in various dermatology and dermatopathology textbooks. The most common titles used for these disorders are diseases of the hair, diseases of cutaneous appendages, folliculitis, acne, and inflammatory lesions of dermis and epidermis. In this chapter, first of all we will discuss folliculitis, and then acne vulgaris that is a kind of folliculitis will be described. After acne vulgaris, other acneiform eruptions and demodicosis will be studied. At the end, simple algorithmic schemes by assembling clinical, pathological, and microbiological data will be shared.
- acneiform lesions
- histopathologic evaluation
1.1. Histology of pilar unit
Pilar unit is a structure generally made up of three subunits which are hair follicle, sebaceous gland, and arrector pili muscle. Hair follicle is divided in to three parts: infundibulum, isthmus, and inferior part. Infundibulum extends between entrance of sebaceous gland duct to the follicular orifice in epidermis. Isthmus: extends between entrance of sebaceous duct to hair follicle and insertion of arrector pili muscle. The basal part of hair follicle is called the inferior segment or inferior part. Histologic structure and function of hair follicle is very intriguing.
The life cycle of hair follicle is divided into three phases: anagen (growth phase), catagen (regressing phase), and telogen (resting phase). The sebaceous gland attached to hair follicle produces holocrine-type secretions. They excrete the sebum through excretory ducts into hair follicle . Sebum that inhibits the reproduction of bacteria and fungi is rich in triglyceride. When the increased number of
1.2. Routine clinical and pathological conditions
There are bazillion hair and pilosebaceous units on the body surface. As a matter of course, hair follicle-related pathologies (especially inflammatory diseases) comprise one of the most popular topics in dermatology clinics.
In a big pathology center where daily around 40 cases of skin materials and annually a total of 35,000–40,000 different biopsy materials are examined, we rarely do histopathologic examination of disorders in inflammatory pilosebaceous units. It is mainly because the clinicians diagnose clinically and do not need much tissue correlation with their differential diagnosis in these disorders.
We retrospectively searched the information system of our hospital for the last 3 years and found 154 reports in which the term “acne” was aforementioned (132 cases were categorized as acne rosacea). For the last 3 years, approximately 23,000 skin samples have been sent by dermatology or plastic and reconstructive surgery departments (punch biopsies, shave biopsies, incisional biopsies, excisional biopsies included). Although general approach do not persuade for biopsy, sometimes in our clinic there is a little tendency to biopsying central face lesions for differential diagnosis.
2. Histopathology of acneiform lesions
2.1. Folliculitis, subtypes, differential diagnosis
In follicular eruptions adnexocentric inflammation, microabscesses and pustules on epidermis can be seen . Peri- and intrafollicular inflammatory cells consist: lymphocytes, plasmocytes, histiocytes, polymorphonuclear, leukocytes, and multinuclear giant cells. Most folliculitis emerges as a result of follicular orifice occlusion by normal flora of the skin.
Although different categorization can be found in various textbooks, folliculitis can be divided into two groups: infectious and noninfectious (sterile). Furthermore noninfectious folliculitis can be grouped as neutrophilic, eosinophilic, etc. according to the predominant cell component present in the lesion. Infectious folliculitis can be grouped as bacterial (Gram-negative, Gram-positive), fungal, viral, and symbiotic (demodex) folliculitis .
The most common cause of Gram-positive folliculitis is
According to some other studies, folliculitis can be classified as superficial and both superficial and deep .
Independent of etiology, the primer lesion of folliculitis is generally an erythematous papule or pustule. Histologically in all types of folliculitis, inflammation is seen either in follicular epithelia and/or perifollicular area (Figure 1).
Whenever the cause is a bacterium, a neutrophilic infiltrate is dominantly seen in the follicular epithelia and dermis (Figure 2). Granuloma formation can be seen in consequence of follicular epithelial rupture and passing of pilosebaceous unit components into the dermis.
In viral folliculitis, cytopathic effects such as acantolysis, dyskeratosis, multinucleation, inclusions, chromatin marginalization, nuclear molding, etc., can be seen in infundibulum. In early lesions, cytopathic effects cannot be seen . In a viral folliculitis, a lower concentration of inflammation is noticeable. In some cases, hyperplasia of epidermis, necrosis of follicular epithelia or sebaceous gland can be visible.
Fungal folliculitis is commonly seen in adult women living in warm and humid climates. Immunosuppression, diabetes and antibiotic use can be predisposing factors. The cause is mostly
In the syphilitic folliculitis, plasma cells are dominant .
There are some possible and practical methods for finding the cause of folliculitis such as: Gram staining (for bacteria), PAS or silver stain (for fungi) and immunohistochemistry (for viral causes). However, the sensitivity of these methods can be low. The more sensitive and specific methods such as fresh tissue culture, PCR, etc., can be used for microorganism typology .
Folliculitis can also be classified according to microanatomic structure of the skin which is involved. Most of bacterial folliculitis involves the superficial part of hair follicle that is why they are called superficial bacterial folliculitis. The superficial folliculitis caused by
In some textbooks the term “acneiform folliculitis” can be seen. This term means that there is an acneiform dilatation in the hair follicle (e.g., pityrosporum folliculitis).
In demodex folliculitis, besides the mites located inside the hair follicle, follicular spongiosis, perifollicular lymphohistiocytic inflammation also draws attention. An isolated folliculitis is generally self-limited. In old and advanced lesions of all folliculitis perifollicular fibrosis can be visible.
When clinically folliculitis is among the differential diagnosis but histopathologically the lesion is not seen in biopsy sections, deeper and serial sections must be taken. When histopathologically folliculitis diagnosis is made but no microorganism is detected, additional histochemical and immunohistochemical stains can be implemented. Acneiform lesions should be thought primarily when no microorganisms detected microscopically and by applying additional methods (culture, etc.). On the other hand, for diagnosis of acneiform lesions a hundred percent clinical correlation is required.
During investigation if a microorganism is detected, cure rate is very high with appropriate treatment (topical antibiotic, topical antifungal, and systemic antiviral drugs).
2.2. Special types of folliculitis and acneiform eruptions
Eosinophils are predominant in some kinds of folliculitis. When eosinophils are predominantly seen in folliculitis, the first step should not be searching for microorganisms
Histopathologically follicle infundibulum is surrounded by inflammation which is predominantly composed of eosinophils and few lymphocytes. The follicle can be ruptured but granuloma formation is not expected. In the past few years, studies have recommended exclusion of fungal folliculitis with PAS-D and/or GMS (Gomori methenamine silver) staining. Eosinophilia in peripheral blood and increased serum IgE levels can be detected in eosinophilic folliculitis. There is also a self-limiting variant of eosinophilic folliculitis presenting on the scalp of children with numerous papules and pustules.
Some authors accept
There are some acne forms that are induced or developed by drugs, sunlight exposure, impulsive skin picking, or different materials.
Overuse of bromides triggers severe acneiform lesions which is called
Chemical exposure to mineral oils and dioxin can cause acneiform eruptions predominantly comedones, this is called
Acneiform lesions can be seen both in Behcet’s and Wegener’s diseases.
In conclusion, a comprehensive dermatological examination and detailed history taking is indispensable in all clinical entities mentioned above.
Flowchart 1 summarizes all the above-mentioned clinical entities.
2.3. Acne vulgaris/pimples
Acne vulgaris is the prototype of acneiform lesions and is the inflammatory disease of sweat glands and pilosebaceous units, mostly observed in teenagers and young adults. In contrast to age predilection, race and sex predilection do not exist. The clinical course is severe in male patients . Acne lesions favor forehead, chin, cheek, chest, shoulder, and back. Family history may be present. In most patients, the lesions regress in a few years period.
The lesions are generally presented as erythematous papules, pustules, blackheads, and whiteheads. In severe cases, tender and painful nodules and cysts can be apparent. Because hair follicle is plugged with keratin, excreted sebum is accumulated in addition to
Acne vulgaris lesions are studied in two groups: noninflammatory (blackheads and whiteheads or comedones) and inflammatory (folliculitis, etc.). Acne lesions can end up with postinflammatory hyperpigmentation and scars (Figures 6–8). Keloid formation is quite rare.
Acne is diagnosed clinically, and biopsy confirmation is generally not required. Histopathologically noninflammatory lesions (comedones) are a kind of follicular retention cysts. These tiny cysts may consist of cornified cells, hair shafts, sebum,
Inflammatory lesions may progress in the following pattern: papule→pustule→nodule→cyst.
Comedonal lesions due to retention the follicular wall is quite thin and the follicular content oozes into adjacent dermis which in turn causes accumulation of inflammatory cells in dermis. This process plays the major role in the formation of inflammatory lesions. When the follicle wall becomes much thinner, the follicle may rupture and lead to pustule (Figure 13) and by the time, nodule formation is in deep dermis. Depending on follicular damage and severity of inflammatory response scar formation, dermal necrosis, and confluent abscesses formation can be observed. Perifollicular elastolysis can be noticed in acne vulgaris scars .
In a noninflammatory lesion if the follicular opening does not expand the follicular wall becomes thinner thus follicular rupture becomes inevitable . Spongiosis is noticeable in follicular epithelia of both inflammatory and noninflammatory lesions. In inflammatory lesions the inflammatory cells attacking follicular epithelia or perifollicular inflammatory cells are composed of mixed type cells (polymorphonuclear leucocytes, lymphocytes, histiocytes). Foreign-body-type multinuclear giant cells and/or granulomatous reactions can be observed as a result of follicular rupture (Figure 14).
2.4. Acne rosacea (adult onset acne)
Rosacea is a disease characterized by macular erythema and flushing of central face generally affecting adult population. Some authors classify acne rosacea as a vascular and follicular disease. In a true rosacea, typical acneiform lesions such as papules and pustules are observed. However, comedones are not an important component of acne rosacea. In contrast to acne vulgaris, increased sebum is not the subject in acne rosacea. Sometimes acne rosacea can lead to blepharitis and phyma formation. In acne rosacea, flushing can be triggered by warmth, cold, alcohol intake, and spicy foods. Granulomatous lesions can be confronted within acne rosacea which present as yellow-brown nodular lesions .
Histopathological findings differ according to the stage of disorder.
In early nonpustular lesions, telangiectasia is in the foreground also perifollicular and perivascular mixed type inflammation (lymphocytes, plasmocytes, macrophages, eosinophils, and polymorphonuclear leucocytes) draw attention (Figures 15 and 16). Abnormal dermal vessel regulation hypothesis is postulated but there is no objective method for evaluating telangiectasia [11, 12]
Acne rosacea can rarely be extrafascial and/or generalized . Acne rosacea more commonly affects women who have type 1 celtic descent skin phenotype. Some methods are present for clinical staging and severity scoring of acne rosacea [2, 13].
In pustular lesions, an increased amount of polymorphonuclear leucocytes are observed. In severe rosacea (rosacea fulminans, pyoderma faciale), polymorphonuclear leucocytes are predominant cells. In the epithelia of hair follicle, spongiosis can be seen in infundibulum part (Figure 17). Follicular rupture can cause granulomatous reactions. Sometimes caseification necrosis can be observed in the center of granulomatous reaction. Solar elastosis can be generally present in rosacea lesions. However, solar elastosis can be a coincidence rather than a specific finding of acne rosacea because solar elastosis is generally present in patients above 40 years of age, in addition to central face is under dense exposure of sunlight throughout life .
In order to reach this stage, episodic flushing → persistent flushing → papulopustular stages must be passed.
In the histopathologically evaluation of rhinophyma, different amounts of lymphocytic inflammation, sebaceous hypertrophy, nodular ectatic vessels, hyperkeratosis , fibrosis, solar elastosis , and mucin accumulation can be observed . Rhinophyma is generally irreversible and surgical intervention is required.
Telangiectatic vascular structures surrounding the rhinophymatous papules may evoke the suspicion of basal cell carcinoma for a clinician . In this case, a biopsy can be done for the exclusion of basal cell carcinoma.
In granulomatous rosacea where long-term phymatous lesions are present in the face,
3. Demodex and demodicosis
Demodex can be found in the normal fauna of the pilosebaceous unit. For this reason, generally it is not mentioned in the pathology reports. However, changing degrees of inflammatory reactions (from accumulation of lymphocytes up to suppurative and granulomatous reactions) are related to demodex mites . Demodex favors sebaceous areas. Density of demodex mites increases with age.
Two species of demodex inhabit in human:
Life cycle of demodex mite is as follows: ova→larvae→protonymph→nymph→adult .
The aid of its mouth,
In 1993 Bonnar et al. , removed the stratum corneum of the skin by the help of cyanoacrylate glue and investigated the follicular contents. The mite count was significantly increased in patients who had acne rosacea compared to normal people. This study showed the relation between acne rosacea and demodex mites. This study is one of the studies that conclude the relationship between acne rosacea and demodex mites .
The pathogenetic mechanisms of Demodex in rosacea can be:
foreign body reaction against the parasite
immune reaction of the host toward the parasite
the parasite serving as a vector for bacteria .
Clinically demodicosis also can be divided into primary and secondary demodicosis.
Secondary demodicosis: more than 30% of the face is affected. Signs and symptoms of the disease are present (erythema, pruritus, etc.), this clinic course is thought to be induced by
Furthermore, there are three forms of traditionally identified demodicosis:
rosacea like demodicosis,
demodicosis gravis .
In Flowcharts 2 and 3, we tried to establish a simple algorithm for making diagnosis easier.