Patient Presentation
A 59-year-old African-American male presented to the dermatology clinic complaining of pus-producing “boils” in the axilla and groin for 40 years as well as new pus-producing “bumps” on the scalp, face, and buttocks over the last year. Upon physical examination, the patient had multiple non-fluctuant, soft nodules and cysts with sinus tracts located in the bilateral axilla and groin with significant secondary scarring. Also, his scalp had scattered keloidal, red papulo-pustules with underlying alopecia. In addition, his buttocks had multiple non-fluctuant papulonodules with a midline scar over the sacrum from previous surgical excision of a “cyst.” His past medical history is significant for a 40-year history of palmar-plantar psoriasis and mild psoriatic arthritis. The relevant family history was a sister with psoriasis.
What’s Your Diagnosis?
Diagnosis: FOLLICULAR OCCLUSION TETRAD (ACNE TETRAD)
In 1956, Pillsbury, Shelley, and Kligman coined the term “follicular occlusion triad” to describe the collection of acne conglobata, hidradenitis suppurativa (HS), and dissecting cellulitis of the scalp in their patients.1 Initially, this term was coined to characterize the “follicular hyperkeratinization” as the underlying pathology of these diseases. Importantly, in 1975, Plewig and Kligman incorporated a final component, the pilonidal sinus, to this clinical presentation and changed the nomenclature to “follicular occlusion tetrad.”2 Even today, many names are used in the literature for this group of disorders, including acne triad, acne tetrad, acne inversa, HS, and so on.1-5
Clinical Features
To better understand these conditions, we have provided an overview of each of the clinical entities observed in this special cluster of skin diseases.
Patients may present with only one of the above conditions or with multiple components of this follicular occlusion tetrad, but rarely with all four components as seen in our patient.
This patient’s clinical features revealed all of the major components of the tetrad: HP (recurrent pus-producing nodules in the groin and axilla with extensive scarring), acne conglobata (pus-producing nodules of the face and buttocks with scarring), dissecting cellulitis of the scalp (scattered scalp papulo-pustules with patchy alopecia), and a pilonidal cyst (scar on the sacrum from surgically removed sinus). Notably, our patient had a distinctive presentation with acne conglobata affecting the face, which has been reported in the literature.12
Differential Diagnosis
In this case, a clinical diagnosis alone is often sufficient. In addition, a biopsy can confirm the classical clinical findings. The differential diagnosis may include other diseases with similar presentations to individual features of this tetrad, such as furunculosis, granuloma inguinale, Crohn’s disease, pseudofolliculitis barbae, acne keloidalis, carbuncles, erysipelas, acneiform eruptions, and so forth.13
Disease Associations
The components of the follicular occlusion tetrad have also been observed in association with other medical conditions and/or syndromes, including keratitis, ichthyosis, and deafness (KID) syndrome;14 Dowling-Degos disease;15 synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome;16 pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome,17 Crohn’s disease,18 HIV,19 and even psoriatic arthritis.20 It is notable that our patient had associated palmo-plantar psoriasis and psoriatic arthritis, which have been linked to acne tetrad through the SAPHO syndrome.3
Pathogenesis
There does appear to be a similar pathophysiology underlying these acneiform diseases, primarily with involvement of the hair follicles. Overall, the early stages of these disease processes begin with keratin plugs and/or comedones. Subsequently, there is plugging of follicular orifices, cyst formation, and rupture and spillage of keratin and glandular secretions into the surrounding tissue, producing a significant inflammatory response.14 At this time, the rationale for the severe and chronic inflammation and significant scarring is unknown.
The early explanations for HS focused on inflammation of the apocrine glands as the primary defect; however, more recent evidence suggests that HS is a disease of the terminal follicular epithelium.21-22 It is believed that the initial follicular occlusion may be caused by folliculitis secondary to frictional, chemical, or even mechanical trauma. Other potential contributors that have been examined include genetic factors, obesity, increased androgens, and even cigarette smoking.22 Similarly, acne conglobata usually presents with inflammatory infiltrate around follicles that can disrupt the normal dermal architecture;8 however, the inciting events are still unknown. Interestingly, there have been a few cases reported of lithium-induced HS and acne conglobata.23 Following this central idea, dissecting cellulitis of the scalp quite likely involves follicular blockage. It is thought that the follicle accumulates keratin-based debris, dilates, and then ruptures, releasing both keratin and bacteria into the surrounding tissues, which causes a neutrophilic and granulomatous response.10 Again, this appears to be an inflammatory process with a secondary bacterial infection. Based upon cytokeratin expression, the epithelial structures involved in HS appear to be nearly identical to that of the pilonidal sinus.11 Presently, the explanation describes an acquired etiology for pilonidal sinus, in which a loose hair is implanted into the follicle and initiates a severe inflammatory reaction and subsequent folliculitis.24
Histology
Because HS appears to be a result of follicular occlusion, the histologic evaluation demonstrates cystic epithelium-lined structures containing laminated keratin, along with acute and chronic inflammation and scarring.21 In a similar fashion, acne conglobata generally has a perifollicular inflammatory infiltrate.8 As for dissecting cellulitis of the scalp, there is often an acneiform distension of the follicular infundibula with perifollicular, mixed, neutrophilic and lymphoplasmacytic inflammation. The inflammatory process tends to involve the lower portion of the dermis and the subcutaneous junction, with the lower portion of terminal follicles most affected.25 Histological evaluation of primary pilonidal sinuses showed indentations in the skin containing keratin plugs and debris, which may be connected to hair follicles, producing chronic inflammation.26 Once again, there is a classical pattern of follicular involvement with acute and chronic inflammation.
Treatment
To select the most efficacious therapy for patients with tetrad acne, it is important to consider the overlap of the individual components. Some treatment options can adequately address multiple components, but individual therapies targeting each condition may produce a better response.1 However, some may argue that providing a single treatment to cover multiple problems would better serve patients, allowing for greater compliance and better clinical response.
At this time, no single cure exists for follicular occlusion tetrad, but multiple therapies, including medical and surgical approaches, can help to improve the patients’ symptoms and sometimes induce remission. In general, the medical therapies are not curative, and relapse almost always occurs when treatments are withdrawn. However, they may be very useful both before and after surgical treatment to help reduce inflammation.22
Regardless, it is important to help the patient to understand the chronic, recurrent nature of these conditions. Also, it is essential to acknowledge the significant psychosocial impact of the disease on these individuals. With a better understanding of these conditions, patients can better partner with their physicians to navigate the various available therapeutic approaches.
Conservative Treatment: Overweight or obese patients should be encouraged to lose weight, avoid tight-fitting clothing in affected areas, avoid excessive heat and moisture, and manage stress, as all have been known to worsen HS.13 Initial treatment of HS can often involve warm baths, hydrotherapy, and even topical agents to help reduce bacterial loads.13
Systemic Retinoids: These agents, which work by inhibiting sebaceous gland function and abnormal keratinization, have been used to treat HS,4,13,27-28 acne conglobata,29 and dissecting cellulitis of the scalp,27,30-31 with varying success. Their use is also a helpful adjunct to surgical therapies.22
Biologics: Several of the new biologic therapies have been used for treatment of each of these individual clinical entities. The use of infliximab (Remicade) for treating HS6-7,32-33 is probably the best-described, but infliximab has also been used with some success in acne conglobata.8 Etanercept (Enbrel), another anti-tumor necrosis factor (TNF)-alpha agent, has been shown to be effective in management of HS, demonstrating more than 60% reduction in symptoms.34 Also, there is a case report of the effective control of HS with adalimumab (Humira).35
Antibiotics: Given the high rate of secondary bacterial infections, appropriate management for many of these patients includes the use of topical and/or systemic antibiotic therapies. Certain antibiotics also provide additional anti-inflammatory effects. Thus, treatment of these conditions has consisted of many antibiotic therapies, including topical clindamycin, cephalo-sporins, dicloxacillin, erythryomycin, tetracycline, and others, depending on the patient’s presentation.6,7,13,22
Surgical Interventions: In many cases, successful treatment will include some form laser or surgical therapy to prevent progression of disease. In fact, some authors have reported that only surgery truly has an effect on the natural history of severe HS and may produce more persistent responses.36 Unlike the other components of tetrad acne, the pilonidal sinus does not have a satisfactory response to medical therapies and will commonly require a surgical intervention such as excision with marsupialization, or excision with primary closure, flap procedures, and Z-plasty.24 As for HS and the other acne tetrad entities, simple incision and drainage may provide temporary relief from fluctuant abscesses or simple cysts, but complete excision usually has more effective, long-lasting results.6,7,13 In dissecting cellulitis of the scalp, a similar approach can be used with simple incision and drainage for fluctuant nodules, with reports of successful complete excision in more severe, recalcitrant cases.10,37 Additionally, laser therapy has shown some promise in treating scalp lesions,38 acne conglobata,39 and pilonidal sinus.40
Other Therapies: Many other therapies have been described in the literature for the varied presentations and severities of these clinical entities, including corticosteroids (topical, intralesional, systemic), cyclo-sporine, colchicine, anti-androgens, finasteride, oral contraceptives, zinc, and intramuscular immune globulin.6-7,9-10,13,22,28,41
Planned Treatment
In the particular case of our patient, who manifested acne tetrad as well as psoriasis and psoriatic arthritis, we are planning to commence anti-TNF-alpha biologic therapy and/or a systemic retinoid, which have been successfully utilized for both entities in the literature.
A 59-year-old African-American male presented to the dermatology clinic complaining of pus-producing “boils” in the axilla and groin for 40 years as well as new pus-producing “bumps” on the scalp, face, and buttocks over the last year. Upon physical examination, the patient had multiple non-fluctuant, soft nodules and cysts with sinus tracts located in the bilateral axilla and groin with significant secondary scarring. Also, his scalp had scattered keloidal, red papulo-pustules with underlying alopecia. In addition, his buttocks had multiple non-fluctuant papulonodules with a midline scar over the sacrum from previous surgical excision of a “cyst.” His past medical history is significant for a 40-year history of palmar-plantar psoriasis and mild psoriatic arthritis. The relevant family history was a sister with psoriasis.
What’s Your Diagnosis?
Diagnosis: FOLLICULAR OCCLUSION TETRAD (ACNE TETRAD)
In 1956, Pillsbury, Shelley, and Kligman coined the term “follicular occlusion triad” to describe the collection of acne conglobata, hidradenitis suppurativa (HS), and dissecting cellulitis of the scalp in their patients.1 Initially, this term was coined to characterize the “follicular hyperkeratinization” as the underlying pathology of these diseases. Importantly, in 1975, Plewig and Kligman incorporated a final component, the pilonidal sinus, to this clinical presentation and changed the nomenclature to “follicular occlusion tetrad.”2 Even today, many names are used in the literature for this group of disorders, including acne triad, acne tetrad, acne inversa, HS, and so on.1-5
Clinical Features
To better understand these conditions, we have provided an overview of each of the clinical entities observed in this special cluster of skin diseases.
Patients may present with only one of the above conditions or with multiple components of this follicular occlusion tetrad, but rarely with all four components as seen in our patient.
This patient’s clinical features revealed all of the major components of the tetrad: HP (recurrent pus-producing nodules in the groin and axilla with extensive scarring), acne conglobata (pus-producing nodules of the face and buttocks with scarring), dissecting cellulitis of the scalp (scattered scalp papulo-pustules with patchy alopecia), and a pilonidal cyst (scar on the sacrum from surgically removed sinus). Notably, our patient had a distinctive presentation with acne conglobata affecting the face, which has been reported in the literature.12
Differential Diagnosis
In this case, a clinical diagnosis alone is often sufficient. In addition, a biopsy can confirm the classical clinical findings. The differential diagnosis may include other diseases with similar presentations to individual features of this tetrad, such as furunculosis, granuloma inguinale, Crohn’s disease, pseudofolliculitis barbae, acne keloidalis, carbuncles, erysipelas, acneiform eruptions, and so forth.13
Disease Associations
The components of the follicular occlusion tetrad have also been observed in association with other medical conditions and/or syndromes, including keratitis, ichthyosis, and deafness (KID) syndrome;14 Dowling-Degos disease;15 synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome;16 pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome,17 Crohn’s disease,18 HIV,19 and even psoriatic arthritis.20 It is notable that our patient had associated palmo-plantar psoriasis and psoriatic arthritis, which have been linked to acne tetrad through the SAPHO syndrome.3
Pathogenesis
There does appear to be a similar pathophysiology underlying these acneiform diseases, primarily with involvement of the hair follicles. Overall, the early stages of these disease processes begin with keratin plugs and/or comedones. Subsequently, there is plugging of follicular orifices, cyst formation, and rupture and spillage of keratin and glandular secretions into the surrounding tissue, producing a significant inflammatory response.14 At this time, the rationale for the severe and chronic inflammation and significant scarring is unknown.
The early explanations for HS focused on inflammation of the apocrine glands as the primary defect; however, more recent evidence suggests that HS is a disease of the terminal follicular epithelium.21-22 It is believed that the initial follicular occlusion may be caused by folliculitis secondary to frictional, chemical, or even mechanical trauma. Other potential contributors that have been examined include genetic factors, obesity, increased androgens, and even cigarette smoking.22 Similarly, acne conglobata usually presents with inflammatory infiltrate around follicles that can disrupt the normal dermal architecture;8 however, the inciting events are still unknown. Interestingly, there have been a few cases reported of lithium-induced HS and acne conglobata.23 Following this central idea, dissecting cellulitis of the scalp quite likely involves follicular blockage. It is thought that the follicle accumulates keratin-based debris, dilates, and then ruptures, releasing both keratin and bacteria into the surrounding tissues, which causes a neutrophilic and granulomatous response.10 Again, this appears to be an inflammatory process with a secondary bacterial infection. Based upon cytokeratin expression, the epithelial structures involved in HS appear to be nearly identical to that of the pilonidal sinus.11 Presently, the explanation describes an acquired etiology for pilonidal sinus, in which a loose hair is implanted into the follicle and initiates a severe inflammatory reaction and subsequent folliculitis.24
Histology
Because HS appears to be a result of follicular occlusion, the histologic evaluation demonstrates cystic epithelium-lined structures containing laminated keratin, along with acute and chronic inflammation and scarring.21 In a similar fashion, acne conglobata generally has a perifollicular inflammatory infiltrate.8 As for dissecting cellulitis of the scalp, there is often an acneiform distension of the follicular infundibula with perifollicular, mixed, neutrophilic and lymphoplasmacytic inflammation. The inflammatory process tends to involve the lower portion of the dermis and the subcutaneous junction, with the lower portion of terminal follicles most affected.25 Histological evaluation of primary pilonidal sinuses showed indentations in the skin containing keratin plugs and debris, which may be connected to hair follicles, producing chronic inflammation.26 Once again, there is a classical pattern of follicular involvement with acute and chronic inflammation.
Treatment
To select the most efficacious therapy for patients with tetrad acne, it is important to consider the overlap of the individual components. Some treatment options can adequately address multiple components, but individual therapies targeting each condition may produce a better response.1 However, some may argue that providing a single treatment to cover multiple problems would better serve patients, allowing for greater compliance and better clinical response.
At this time, no single cure exists for follicular occlusion tetrad, but multiple therapies, including medical and surgical approaches, can help to improve the patients’ symptoms and sometimes induce remission. In general, the medical therapies are not curative, and relapse almost always occurs when treatments are withdrawn. However, they may be very useful both before and after surgical treatment to help reduce inflammation.22
Regardless, it is important to help the patient to understand the chronic, recurrent nature of these conditions. Also, it is essential to acknowledge the significant psychosocial impact of the disease on these individuals. With a better understanding of these conditions, patients can better partner with their physicians to navigate the various available therapeutic approaches.
Conservative Treatment: Overweight or obese patients should be encouraged to lose weight, avoid tight-fitting clothing in affected areas, avoid excessive heat and moisture, and manage stress, as all have been known to worsen HS.13 Initial treatment of HS can often involve warm baths, hydrotherapy, and even topical agents to help reduce bacterial loads.13
Systemic Retinoids: These agents, which work by inhibiting sebaceous gland function and abnormal keratinization, have been used to treat HS,4,13,27-28 acne conglobata,29 and dissecting cellulitis of the scalp,27,30-31 with varying success. Their use is also a helpful adjunct to surgical therapies.22
Biologics: Several of the new biologic therapies have been used for treatment of each of these individual clinical entities. The use of infliximab (Remicade) for treating HS6-7,32-33 is probably the best-described, but infliximab has also been used with some success in acne conglobata.8 Etanercept (Enbrel), another anti-tumor necrosis factor (TNF)-alpha agent, has been shown to be effective in management of HS, demonstrating more than 60% reduction in symptoms.34 Also, there is a case report of the effective control of HS with adalimumab (Humira).35
Antibiotics: Given the high rate of secondary bacterial infections, appropriate management for many of these patients includes the use of topical and/or systemic antibiotic therapies. Certain antibiotics also provide additional anti-inflammatory effects. Thus, treatment of these conditions has consisted of many antibiotic therapies, including topical clindamycin, cephalo-sporins, dicloxacillin, erythryomycin, tetracycline, and others, depending on the patient’s presentation.6,7,13,22
Surgical Interventions: In many cases, successful treatment will include some form laser or surgical therapy to prevent progression of disease. In fact, some authors have reported that only surgery truly has an effect on the natural history of severe HS and may produce more persistent responses.36 Unlike the other components of tetrad acne, the pilonidal sinus does not have a satisfactory response to medical therapies and will commonly require a surgical intervention such as excision with marsupialization, or excision with primary closure, flap procedures, and Z-plasty.24 As for HS and the other acne tetrad entities, simple incision and drainage may provide temporary relief from fluctuant abscesses or simple cysts, but complete excision usually has more effective, long-lasting results.6,7,13 In dissecting cellulitis of the scalp, a similar approach can be used with simple incision and drainage for fluctuant nodules, with reports of successful complete excision in more severe, recalcitrant cases.10,37 Additionally, laser therapy has shown some promise in treating scalp lesions,38 acne conglobata,39 and pilonidal sinus.40
Other Therapies: Many other therapies have been described in the literature for the varied presentations and severities of these clinical entities, including corticosteroids (topical, intralesional, systemic), cyclo-sporine, colchicine, anti-androgens, finasteride, oral contraceptives, zinc, and intramuscular immune globulin.6-7,9-10,13,22,28,41
Planned Treatment
In the particular case of our patient, who manifested acne tetrad as well as psoriasis and psoriatic arthritis, we are planning to commence anti-TNF-alpha biologic therapy and/or a systemic retinoid, which have been successfully utilized for both entities in the literature.
A 59-year-old African-American male presented to the dermatology clinic complaining of pus-producing “boils” in the axilla and groin for 40 years as well as new pus-producing “bumps” on the scalp, face, and buttocks over the last year. Upon physical examination, the patient had multiple non-fluctuant, soft nodules and cysts with sinus tracts located in the bilateral axilla and groin with significant secondary scarring. Also, his scalp had scattered keloidal, red papulo-pustules with underlying alopecia. In addition, his buttocks had multiple non-fluctuant papulonodules with a midline scar over the sacrum from previous surgical excision of a “cyst.” His past medical history is significant for a 40-year history of palmar-plantar psoriasis and mild psoriatic arthritis. The relevant family history was a sister with psoriasis.
What’s Your Diagnosis?
,
Patient Presentation
A 59-year-old African-American male presented to the dermatology clinic complaining of pus-producing “boils” in the axilla and groin for 40 years as well as new pus-producing “bumps” on the scalp, face, and buttocks over the last year. Upon physical examination, the patient had multiple non-fluctuant, soft nodules and cysts with sinus tracts located in the bilateral axilla and groin with significant secondary scarring. Also, his scalp had scattered keloidal, red papulo-pustules with underlying alopecia. In addition, his buttocks had multiple non-fluctuant papulonodules with a midline scar over the sacrum from previous surgical excision of a “cyst.” His past medical history is significant for a 40-year history of palmar-plantar psoriasis and mild psoriatic arthritis. The relevant family history was a sister with psoriasis.
What’s Your Diagnosis?
Diagnosis: FOLLICULAR OCCLUSION TETRAD (ACNE TETRAD)
In 1956, Pillsbury, Shelley, and Kligman coined the term “follicular occlusion triad” to describe the collection of acne conglobata, hidradenitis suppurativa (HS), and dissecting cellulitis of the scalp in their patients.1 Initially, this term was coined to characterize the “follicular hyperkeratinization” as the underlying pathology of these diseases. Importantly, in 1975, Plewig and Kligman incorporated a final component, the pilonidal sinus, to this clinical presentation and changed the nomenclature to “follicular occlusion tetrad.”2 Even today, many names are used in the literature for this group of disorders, including acne triad, acne tetrad, acne inversa, HS, and so on.1-5
Clinical Features
To better understand these conditions, we have provided an overview of each of the clinical entities observed in this special cluster of skin diseases.
Patients may present with only one of the above conditions or with multiple components of this follicular occlusion tetrad, but rarely with all four components as seen in our patient.
This patient’s clinical features revealed all of the major components of the tetrad: HP (recurrent pus-producing nodules in the groin and axilla with extensive scarring), acne conglobata (pus-producing nodules of the face and buttocks with scarring), dissecting cellulitis of the scalp (scattered scalp papulo-pustules with patchy alopecia), and a pilonidal cyst (scar on the sacrum from surgically removed sinus). Notably, our patient had a distinctive presentation with acne conglobata affecting the face, which has been reported in the literature.12
Differential Diagnosis
In this case, a clinical diagnosis alone is often sufficient. In addition, a biopsy can confirm the classical clinical findings. The differential diagnosis may include other diseases with similar presentations to individual features of this tetrad, such as furunculosis, granuloma inguinale, Crohn’s disease, pseudofolliculitis barbae, acne keloidalis, carbuncles, erysipelas, acneiform eruptions, and so forth.13
Disease Associations
The components of the follicular occlusion tetrad have also been observed in association with other medical conditions and/or syndromes, including keratitis, ichthyosis, and deafness (KID) syndrome;14 Dowling-Degos disease;15 synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome;16 pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome,17 Crohn’s disease,18 HIV,19 and even psoriatic arthritis.20 It is notable that our patient had associated palmo-plantar psoriasis and psoriatic arthritis, which have been linked to acne tetrad through the SAPHO syndrome.3
Pathogenesis
There does appear to be a similar pathophysiology underlying these acneiform diseases, primarily with involvement of the hair follicles. Overall, the early stages of these disease processes begin with keratin plugs and/or comedones. Subsequently, there is plugging of follicular orifices, cyst formation, and rupture and spillage of keratin and glandular secretions into the surrounding tissue, producing a significant inflammatory response.14 At this time, the rationale for the severe and chronic inflammation and significant scarring is unknown.
The early explanations for HS focused on inflammation of the apocrine glands as the primary defect; however, more recent evidence suggests that HS is a disease of the terminal follicular epithelium.21-22 It is believed that the initial follicular occlusion may be caused by folliculitis secondary to frictional, chemical, or even mechanical trauma. Other potential contributors that have been examined include genetic factors, obesity, increased androgens, and even cigarette smoking.22 Similarly, acne conglobata usually presents with inflammatory infiltrate around follicles that can disrupt the normal dermal architecture;8 however, the inciting events are still unknown. Interestingly, there have been a few cases reported of lithium-induced HS and acne conglobata.23 Following this central idea, dissecting cellulitis of the scalp quite likely involves follicular blockage. It is thought that the follicle accumulates keratin-based debris, dilates, and then ruptures, releasing both keratin and bacteria into the surrounding tissues, which causes a neutrophilic and granulomatous response.10 Again, this appears to be an inflammatory process with a secondary bacterial infection. Based upon cytokeratin expression, the epithelial structures involved in HS appear to be nearly identical to that of the pilonidal sinus.11 Presently, the explanation describes an acquired etiology for pilonidal sinus, in which a loose hair is implanted into the follicle and initiates a severe inflammatory reaction and subsequent folliculitis.24
Histology
Because HS appears to be a result of follicular occlusion, the histologic evaluation demonstrates cystic epithelium-lined structures containing laminated keratin, along with acute and chronic inflammation and scarring.21 In a similar fashion, acne conglobata generally has a perifollicular inflammatory infiltrate.8 As for dissecting cellulitis of the scalp, there is often an acneiform distension of the follicular infundibula with perifollicular, mixed, neutrophilic and lymphoplasmacytic inflammation. The inflammatory process tends to involve the lower portion of the dermis and the subcutaneous junction, with the lower portion of terminal follicles most affected.25 Histological evaluation of primary pilonidal sinuses showed indentations in the skin containing keratin plugs and debris, which may be connected to hair follicles, producing chronic inflammation.26 Once again, there is a classical pattern of follicular involvement with acute and chronic inflammation.
Treatment
To select the most efficacious therapy for patients with tetrad acne, it is important to consider the overlap of the individual components. Some treatment options can adequately address multiple components, but individual therapies targeting each condition may produce a better response.1 However, some may argue that providing a single treatment to cover multiple problems would better serve patients, allowing for greater compliance and better clinical response.
At this time, no single cure exists for follicular occlusion tetrad, but multiple therapies, including medical and surgical approaches, can help to improve the patients’ symptoms and sometimes induce remission. In general, the medical therapies are not curative, and relapse almost always occurs when treatments are withdrawn. However, they may be very useful both before and after surgical treatment to help reduce inflammation.22
Regardless, it is important to help the patient to understand the chronic, recurrent nature of these conditions. Also, it is essential to acknowledge the significant psychosocial impact of the disease on these individuals. With a better understanding of these conditions, patients can better partner with their physicians to navigate the various available therapeutic approaches.
Conservative Treatment: Overweight or obese patients should be encouraged to lose weight, avoid tight-fitting clothing in affected areas, avoid excessive heat and moisture, and manage stress, as all have been known to worsen HS.13 Initial treatment of HS can often involve warm baths, hydrotherapy, and even topical agents to help reduce bacterial loads.13
Systemic Retinoids: These agents, which work by inhibiting sebaceous gland function and abnormal keratinization, have been used to treat HS,4,13,27-28 acne conglobata,29 and dissecting cellulitis of the scalp,27,30-31 with varying success. Their use is also a helpful adjunct to surgical therapies.22
Biologics: Several of the new biologic therapies have been used for treatment of each of these individual clinical entities. The use of infliximab (Remicade) for treating HS6-7,32-33 is probably the best-described, but infliximab has also been used with some success in acne conglobata.8 Etanercept (Enbrel), another anti-tumor necrosis factor (TNF)-alpha agent, has been shown to be effective in management of HS, demonstrating more than 60% reduction in symptoms.34 Also, there is a case report of the effective control of HS with adalimumab (Humira).35
Antibiotics: Given the high rate of secondary bacterial infections, appropriate management for many of these patients includes the use of topical and/or systemic antibiotic therapies. Certain antibiotics also provide additional anti-inflammatory effects. Thus, treatment of these conditions has consisted of many antibiotic therapies, including topical clindamycin, cephalo-sporins, dicloxacillin, erythryomycin, tetracycline, and others, depending on the patient’s presentation.6,7,13,22
Surgical Interventions: In many cases, successful treatment will include some form laser or surgical therapy to prevent progression of disease. In fact, some authors have reported that only surgery truly has an effect on the natural history of severe HS and may produce more persistent responses.36 Unlike the other components of tetrad acne, the pilonidal sinus does not have a satisfactory response to medical therapies and will commonly require a surgical intervention such as excision with marsupialization, or excision with primary closure, flap procedures, and Z-plasty.24 As for HS and the other acne tetrad entities, simple incision and drainage may provide temporary relief from fluctuant abscesses or simple cysts, but complete excision usually has more effective, long-lasting results.6,7,13 In dissecting cellulitis of the scalp, a similar approach can be used with simple incision and drainage for fluctuant nodules, with reports of successful complete excision in more severe, recalcitrant cases.10,37 Additionally, laser therapy has shown some promise in treating scalp lesions,38 acne conglobata,39 and pilonidal sinus.40
Other Therapies: Many other therapies have been described in the literature for the varied presentations and severities of these clinical entities, including corticosteroids (topical, intralesional, systemic), cyclo-sporine, colchicine, anti-androgens, finasteride, oral contraceptives, zinc, and intramuscular immune globulin.6-7,9-10,13,22,28,41
Planned Treatment
In the particular case of our patient, who manifested acne tetrad as well as psoriasis and psoriatic arthritis, we are planning to commence anti-TNF-alpha biologic therapy and/or a systemic retinoid, which have been successfully utilized for both entities in the literature.
A 59-year-old African-American male presented to the dermatology clinic complaining of pus-producing “boils” in the axilla and groin for 40 years as well as new pus-producing “bumps” on the scalp, face, and buttocks over the last year. Upon physical examination, the patient had multiple non-fluctuant, soft nodules and cysts with sinus tracts located in the bilateral axilla and groin with significant secondary scarring. Also, his scalp had scattered keloidal, red papulo-pustules with underlying alopecia. In addition, his buttocks had multiple non-fluctuant papulonodules with a midline scar over the sacrum from previous surgical excision of a “cyst.” His past medical history is significant for a 40-year history of palmar-plantar psoriasis and mild psoriatic arthritis. The relevant family history was a sister with psoriasis.
What’s Your Diagnosis?
Diagnosis: FOLLICULAR OCCLUSION TETRAD (ACNE TETRAD)
In 1956, Pillsbury, Shelley, and Kligman coined the term “follicular occlusion triad” to describe the collection of acne conglobata, hidradenitis suppurativa (HS), and dissecting cellulitis of the scalp in their patients.1 Initially, this term was coined to characterize the “follicular hyperkeratinization” as the underlying pathology of these diseases. Importantly, in 1975, Plewig and Kligman incorporated a final component, the pilonidal sinus, to this clinical presentation and changed the nomenclature to “follicular occlusion tetrad.”2 Even today, many names are used in the literature for this group of disorders, including acne triad, acne tetrad, acne inversa, HS, and so on.1-5
Clinical Features
To better understand these conditions, we have provided an overview of each of the clinical entities observed in this special cluster of skin diseases.
Patients may present with only one of the above conditions or with multiple components of this follicular occlusion tetrad, but rarely with all four components as seen in our patient.
This patient’s clinical features revealed all of the major components of the tetrad: HP (recurrent pus-producing nodules in the groin and axilla with extensive scarring), acne conglobata (pus-producing nodules of the face and buttocks with scarring), dissecting cellulitis of the scalp (scattered scalp papulo-pustules with patchy alopecia), and a pilonidal cyst (scar on the sacrum from surgically removed sinus). Notably, our patient had a distinctive presentation with acne conglobata affecting the face, which has been reported in the literature.12
Differential Diagnosis
In this case, a clinical diagnosis alone is often sufficient. In addition, a biopsy can confirm the classical clinical findings. The differential diagnosis may include other diseases with similar presentations to individual features of this tetrad, such as furunculosis, granuloma inguinale, Crohn’s disease, pseudofolliculitis barbae, acne keloidalis, carbuncles, erysipelas, acneiform eruptions, and so forth.13
Disease Associations
The components of the follicular occlusion tetrad have also been observed in association with other medical conditions and/or syndromes, including keratitis, ichthyosis, and deafness (KID) syndrome;14 Dowling-Degos disease;15 synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome;16 pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome,17 Crohn’s disease,18 HIV,19 and even psoriatic arthritis.20 It is notable that our patient had associated palmo-plantar psoriasis and psoriatic arthritis, which have been linked to acne tetrad through the SAPHO syndrome.3
Pathogenesis
There does appear to be a similar pathophysiology underlying these acneiform diseases, primarily with involvement of the hair follicles. Overall, the early stages of these disease processes begin with keratin plugs and/or comedones. Subsequently, there is plugging of follicular orifices, cyst formation, and rupture and spillage of keratin and glandular secretions into the surrounding tissue, producing a significant inflammatory response.14 At this time, the rationale for the severe and chronic inflammation and significant scarring is unknown.
The early explanations for HS focused on inflammation of the apocrine glands as the primary defect; however, more recent evidence suggests that HS is a disease of the terminal follicular epithelium.21-22 It is believed that the initial follicular occlusion may be caused by folliculitis secondary to frictional, chemical, or even mechanical trauma. Other potential contributors that have been examined include genetic factors, obesity, increased androgens, and even cigarette smoking.22 Similarly, acne conglobata usually presents with inflammatory infiltrate around follicles that can disrupt the normal dermal architecture;8 however, the inciting events are still unknown. Interestingly, there have been a few cases reported of lithium-induced HS and acne conglobata.23 Following this central idea, dissecting cellulitis of the scalp quite likely involves follicular blockage. It is thought that the follicle accumulates keratin-based debris, dilates, and then ruptures, releasing both keratin and bacteria into the surrounding tissues, which causes a neutrophilic and granulomatous response.10 Again, this appears to be an inflammatory process with a secondary bacterial infection. Based upon cytokeratin expression, the epithelial structures involved in HS appear to be nearly identical to that of the pilonidal sinus.11 Presently, the explanation describes an acquired etiology for pilonidal sinus, in which a loose hair is implanted into the follicle and initiates a severe inflammatory reaction and subsequent folliculitis.24
Histology
Because HS appears to be a result of follicular occlusion, the histologic evaluation demonstrates cystic epithelium-lined structures containing laminated keratin, along with acute and chronic inflammation and scarring.21 In a similar fashion, acne conglobata generally has a perifollicular inflammatory infiltrate.8 As for dissecting cellulitis of the scalp, there is often an acneiform distension of the follicular infundibula with perifollicular, mixed, neutrophilic and lymphoplasmacytic inflammation. The inflammatory process tends to involve the lower portion of the dermis and the subcutaneous junction, with the lower portion of terminal follicles most affected.25 Histological evaluation of primary pilonidal sinuses showed indentations in the skin containing keratin plugs and debris, which may be connected to hair follicles, producing chronic inflammation.26 Once again, there is a classical pattern of follicular involvement with acute and chronic inflammation.
Treatment
To select the most efficacious therapy for patients with tetrad acne, it is important to consider the overlap of the individual components. Some treatment options can adequately address multiple components, but individual therapies targeting each condition may produce a better response.1 However, some may argue that providing a single treatment to cover multiple problems would better serve patients, allowing for greater compliance and better clinical response.
At this time, no single cure exists for follicular occlusion tetrad, but multiple therapies, including medical and surgical approaches, can help to improve the patients’ symptoms and sometimes induce remission. In general, the medical therapies are not curative, and relapse almost always occurs when treatments are withdrawn. However, they may be very useful both before and after surgical treatment to help reduce inflammation.22
Regardless, it is important to help the patient to understand the chronic, recurrent nature of these conditions. Also, it is essential to acknowledge the significant psychosocial impact of the disease on these individuals. With a better understanding of these conditions, patients can better partner with their physicians to navigate the various available therapeutic approaches.
Conservative Treatment: Overweight or obese patients should be encouraged to lose weight, avoid tight-fitting clothing in affected areas, avoid excessive heat and moisture, and manage stress, as all have been known to worsen HS.13 Initial treatment of HS can often involve warm baths, hydrotherapy, and even topical agents to help reduce bacterial loads.13
Systemic Retinoids: These agents, which work by inhibiting sebaceous gland function and abnormal keratinization, have been used to treat HS,4,13,27-28 acne conglobata,29 and dissecting cellulitis of the scalp,27,30-31 with varying success. Their use is also a helpful adjunct to surgical therapies.22
Biologics: Several of the new biologic therapies have been used for treatment of each of these individual clinical entities. The use of infliximab (Remicade) for treating HS6-7,32-33 is probably the best-described, but infliximab has also been used with some success in acne conglobata.8 Etanercept (Enbrel), another anti-tumor necrosis factor (TNF)-alpha agent, has been shown to be effective in management of HS, demonstrating more than 60% reduction in symptoms.34 Also, there is a case report of the effective control of HS with adalimumab (Humira).35
Antibiotics: Given the high rate of secondary bacterial infections, appropriate management for many of these patients includes the use of topical and/or systemic antibiotic therapies. Certain antibiotics also provide additional anti-inflammatory effects. Thus, treatment of these conditions has consisted of many antibiotic therapies, including topical clindamycin, cephalo-sporins, dicloxacillin, erythryomycin, tetracycline, and others, depending on the patient’s presentation.6,7,13,22
Surgical Interventions: In many cases, successful treatment will include some form laser or surgical therapy to prevent progression of disease. In fact, some authors have reported that only surgery truly has an effect on the natural history of severe HS and may produce more persistent responses.36 Unlike the other components of tetrad acne, the pilonidal sinus does not have a satisfactory response to medical therapies and will commonly require a surgical intervention such as excision with marsupialization, or excision with primary closure, flap procedures, and Z-plasty.24 As for HS and the other acne tetrad entities, simple incision and drainage may provide temporary relief from fluctuant abscesses or simple cysts, but complete excision usually has more effective, long-lasting results.6,7,13 In dissecting cellulitis of the scalp, a similar approach can be used with simple incision and drainage for fluctuant nodules, with reports of successful complete excision in more severe, recalcitrant cases.10,37 Additionally, laser therapy has shown some promise in treating scalp lesions,38 acne conglobata,39 and pilonidal sinus.40
Other Therapies: Many other therapies have been described in the literature for the varied presentations and severities of these clinical entities, including corticosteroids (topical, intralesional, systemic), cyclo-sporine, colchicine, anti-androgens, finasteride, oral contraceptives, zinc, and intramuscular immune globulin.6-7,9-10,13,22,28,41
Planned Treatment
In the particular case of our patient, who manifested acne tetrad as well as psoriasis and psoriatic arthritis, we are planning to commence anti-TNF-alpha biologic therapy and/or a systemic retinoid, which have been successfully utilized for both entities in the literature.
Diagnosis: FOLLICULAR OCCLUSION TETRAD (ACNE TETRAD)
In 1956, Pillsbury, Shelley, and Kligman coined the term “follicular occlusion triad” to describe the collection of acne conglobata, hidradenitis suppurativa (HS), and dissecting cellulitis of the scalp in their patients.1 Initially, this term was coined to characterize the “follicular hyperkeratinization” as the underlying pathology of these diseases. Importantly, in 1975, Plewig and Kligman incorporated a final component, the pilonidal sinus, to this clinical presentation and changed the nomenclature to “follicular occlusion tetrad.”2 Even today, many names are used in the literature for this group of disorders, including acne triad, acne tetrad, acne inversa, HS, and so on.1-5
Clinical Features
To better understand these conditions, we have provided an overview of each of the clinical entities observed in this special cluster of skin diseases.
Patients may present with only one of the above conditions or with multiple components of this follicular occlusion tetrad, but rarely with all four components as seen in our patient.
This patient’s clinical features revealed all of the major components of the tetrad: HP (recurrent pus-producing nodules in the groin and axilla with extensive scarring), acne conglobata (pus-producing nodules of the face and buttocks with scarring), dissecting cellulitis of the scalp (scattered scalp papulo-pustules with patchy alopecia), and a pilonidal cyst (scar on the sacrum from surgically removed sinus). Notably, our patient had a distinctive presentation with acne conglobata affecting the face, which has been reported in the literature.12
Differential Diagnosis
In this case, a clinical diagnosis alone is often sufficient. In addition, a biopsy can confirm the classical clinical findings. The differential diagnosis may include other diseases with similar presentations to individual features of this tetrad, such as furunculosis, granuloma inguinale, Crohn’s disease, pseudofolliculitis barbae, acne keloidalis, carbuncles, erysipelas, acneiform eruptions, and so forth.13
Disease Associations
The components of the follicular occlusion tetrad have also been observed in association with other medical conditions and/or syndromes, including keratitis, ichthyosis, and deafness (KID) syndrome;14 Dowling-Degos disease;15 synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome;16 pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome,17 Crohn’s disease,18 HIV,19 and even psoriatic arthritis.20 It is notable that our patient had associated palmo-plantar psoriasis and psoriatic arthritis, which have been linked to acne tetrad through the SAPHO syndrome.3
Pathogenesis
There does appear to be a similar pathophysiology underlying these acneiform diseases, primarily with involvement of the hair follicles. Overall, the early stages of these disease processes begin with keratin plugs and/or comedones. Subsequently, there is plugging of follicular orifices, cyst formation, and rupture and spillage of keratin and glandular secretions into the surrounding tissue, producing a significant inflammatory response.14 At this time, the rationale for the severe and chronic inflammation and significant scarring is unknown.
The early explanations for HS focused on inflammation of the apocrine glands as the primary defect; however, more recent evidence suggests that HS is a disease of the terminal follicular epithelium.21-22 It is believed that the initial follicular occlusion may be caused by folliculitis secondary to frictional, chemical, or even mechanical trauma. Other potential contributors that have been examined include genetic factors, obesity, increased androgens, and even cigarette smoking.22 Similarly, acne conglobata usually presents with inflammatory infiltrate around follicles that can disrupt the normal dermal architecture;8 however, the inciting events are still unknown. Interestingly, there have been a few cases reported of lithium-induced HS and acne conglobata.23 Following this central idea, dissecting cellulitis of the scalp quite likely involves follicular blockage. It is thought that the follicle accumulates keratin-based debris, dilates, and then ruptures, releasing both keratin and bacteria into the surrounding tissues, which causes a neutrophilic and granulomatous response.10 Again, this appears to be an inflammatory process with a secondary bacterial infection. Based upon cytokeratin expression, the epithelial structures involved in HS appear to be nearly identical to that of the pilonidal sinus.11 Presently, the explanation describes an acquired etiology for pilonidal sinus, in which a loose hair is implanted into the follicle and initiates a severe inflammatory reaction and subsequent folliculitis.24
Histology
Because HS appears to be a result of follicular occlusion, the histologic evaluation demonstrates cystic epithelium-lined structures containing laminated keratin, along with acute and chronic inflammation and scarring.21 In a similar fashion, acne conglobata generally has a perifollicular inflammatory infiltrate.8 As for dissecting cellulitis of the scalp, there is often an acneiform distension of the follicular infundibula with perifollicular, mixed, neutrophilic and lymphoplasmacytic inflammation. The inflammatory process tends to involve the lower portion of the dermis and the subcutaneous junction, with the lower portion of terminal follicles most affected.25 Histological evaluation of primary pilonidal sinuses showed indentations in the skin containing keratin plugs and debris, which may be connected to hair follicles, producing chronic inflammation.26 Once again, there is a classical pattern of follicular involvement with acute and chronic inflammation.
Treatment
To select the most efficacious therapy for patients with tetrad acne, it is important to consider the overlap of the individual components. Some treatment options can adequately address multiple components, but individual therapies targeting each condition may produce a better response.1 However, some may argue that providing a single treatment to cover multiple problems would better serve patients, allowing for greater compliance and better clinical response.
At this time, no single cure exists for follicular occlusion tetrad, but multiple therapies, including medical and surgical approaches, can help to improve the patients’ symptoms and sometimes induce remission. In general, the medical therapies are not curative, and relapse almost always occurs when treatments are withdrawn. However, they may be very useful both before and after surgical treatment to help reduce inflammation.22
Regardless, it is important to help the patient to understand the chronic, recurrent nature of these conditions. Also, it is essential to acknowledge the significant psychosocial impact of the disease on these individuals. With a better understanding of these conditions, patients can better partner with their physicians to navigate the various available therapeutic approaches.
Conservative Treatment: Overweight or obese patients should be encouraged to lose weight, avoid tight-fitting clothing in affected areas, avoid excessive heat and moisture, and manage stress, as all have been known to worsen HS.13 Initial treatment of HS can often involve warm baths, hydrotherapy, and even topical agents to help reduce bacterial loads.13
Systemic Retinoids: These agents, which work by inhibiting sebaceous gland function and abnormal keratinization, have been used to treat HS,4,13,27-28 acne conglobata,29 and dissecting cellulitis of the scalp,27,30-31 with varying success. Their use is also a helpful adjunct to surgical therapies.22
Biologics: Several of the new biologic therapies have been used for treatment of each of these individual clinical entities. The use of infliximab (Remicade) for treating HS6-7,32-33 is probably the best-described, but infliximab has also been used with some success in acne conglobata.8 Etanercept (Enbrel), another anti-tumor necrosis factor (TNF)-alpha agent, has been shown to be effective in management of HS, demonstrating more than 60% reduction in symptoms.34 Also, there is a case report of the effective control of HS with adalimumab (Humira).35
Antibiotics: Given the high rate of secondary bacterial infections, appropriate management for many of these patients includes the use of topical and/or systemic antibiotic therapies. Certain antibiotics also provide additional anti-inflammatory effects. Thus, treatment of these conditions has consisted of many antibiotic therapies, including topical clindamycin, cephalo-sporins, dicloxacillin, erythryomycin, tetracycline, and others, depending on the patient’s presentation.6,7,13,22
Surgical Interventions: In many cases, successful treatment will include some form laser or surgical therapy to prevent progression of disease. In fact, some authors have reported that only surgery truly has an effect on the natural history of severe HS and may produce more persistent responses.36 Unlike the other components of tetrad acne, the pilonidal sinus does not have a satisfactory response to medical therapies and will commonly require a surgical intervention such as excision with marsupialization, or excision with primary closure, flap procedures, and Z-plasty.24 As for HS and the other acne tetrad entities, simple incision and drainage may provide temporary relief from fluctuant abscesses or simple cysts, but complete excision usually has more effective, long-lasting results.6,7,13 In dissecting cellulitis of the scalp, a similar approach can be used with simple incision and drainage for fluctuant nodules, with reports of successful complete excision in more severe, recalcitrant cases.10,37 Additionally, laser therapy has shown some promise in treating scalp lesions,38 acne conglobata,39 and pilonidal sinus.40
Other Therapies: Many other therapies have been described in the literature for the varied presentations and severities of these clinical entities, including corticosteroids (topical, intralesional, systemic), cyclo-sporine, colchicine, anti-androgens, finasteride, oral contraceptives, zinc, and intramuscular immune globulin.6-7,9-10,13,22,28,41
Planned Treatment
In the particular case of our patient, who manifested acne tetrad as well as psoriasis and psoriatic arthritis, we are planning to commence anti-TNF-alpha biologic therapy and/or a systemic retinoid, which have been successfully utilized for both entities in the literature.
