Autoinflammatory syndromes associated with hidradenitis suppurativa and/or acne

Autoinflammatory syndromes associated with hidradenitis suppurativa (HS) and/or acne are rare but potentially debilitating disorders if not diagnosed and treated correctly. They share a common pathogenesis involving a dysregulated innate immune system with abnormal interleukin (IL)‐1 signaling leading to sterile neutrophilic inflammation. The clinical features are recurrent episodes of fever, painful arthritis, and skin lesions consistent with HS, acne, and pyoderma gangrenosum (PG) accompanied by elevated systemic inflammatory markers in blood. So far, several clinically different syndromes have been reported in the literature including pyoderma gangrenosum, acne, and pyogenic arthritis (PAPA), pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH), pyoderma gangrenosum, acne, and spondyloarthritis (PASS), pyoderma gangrenosum, acne, pyogenic arthritis, and hidradenitis suppurativa (PAPASH), psoriatic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PsAPASH), and pyoderma gangrenosum, acne, and ulcerative colitis (PAC). The rarity of the syndromes complicates the establishment of evidence‐based treatment guidelines. Furthermore, treatment can be challenging due to lack of response to standard treatment modalities. Therefore, it is important to increase the awareness about these diseases in order to optimize disease management and ultimately improve the quality of life of patients.     

Successful use of brachytherapy for a severe hidradenitis suppurativa variant

Hidradenitis suppurativa is a member of the follicular occlusion tetrad, along with acne conglobata, dissecting cellulitis of the scalp and pilodinal sinus. These conditions share common pathophysiologic features, including follicle occlusion, bacterial overgrowth, severe suppurative inflammation, scarring, and sinus tract formation. Treatment of severe cases is challenging, and a novel treatment modality would be of significant value. We describe a 46‐year‐old man who presented with a 15‐year history of suppurative and scarring nodules involving his groin, scalp, neck, face, and chest. Based on their distribution and morphology, these lesions were most characteristic of hidradenitis suppurativa, although he had features of acne conglobata and dissecting cellulitis as well. Over the years, he had been treated with several antimicrobial and immunomodulatory agents, the main conventional therapies for follicular occlusion syndromes, without much success. We then treated him with superficial brachytherapy to his right groin and occiput, which led to significant improvement. No toxic side effects were noted. This case demonstrates the successful application of superficial brachytherapy for the treatment of severe hidradenitis suppurativa, and possibly for other follicular occlusion syndromes.     

Off‐label use of TNF‐alpha inhibitors in a dermatological university department: retrospective evaluation of 118 patients

Tumor necrosis factor‐alpha (TNF)‐alpha inhibitors are licensed for patients with severe refractory psoriasis and psoriatic arthritis. However, TNF‐alpha inhibitors have also been used off‐label for various recalcitrant mucocutaneous diseases. This study aimed to evaluate the efficacy and safety of TNF‐alpha inhibitors used for off‐label dermatological indications. We retrospectively evaluated patient records of 118 patients treated off‐label with TNF‐alpha inhibitors in a dermatological university department. Patients presented with severe aphthous stomatitis/genital aphthous lesions (26), chronic urticaria (25), hidradenitis suppurativa (29), acne conglobata (11), dissecting cellulitis of the scalp (two), orofacial granulomatosis (four), sarcoidosis (four), granuloma annulare (two), granulomatous rosacea (one), granuloma faciale (one), subcorneal pustulosis (one), pyoderma gangrenosum (four), Sweet's syndrome (four), Well's syndrome (one), benign familial pemphigus (one), lichen planus (one), and folliculitis decalvans (one). A significant number of these patients went into remission during therapy with TNF‐alpha inhibitors. A total of 11 patients (9%) experienced severe adverse effects during therapy. Off‐label therapy with TNF‐alpha inhibitors may be considered for selected patients with severe recalcitrant mucocutaneous diseases. The risk of severe adverse effects signals that a thorough benefit–risk assessment should be performed before initiating off‐label treatment with TNF‐alpha inhibitors for these conditions.     

Pyoderma gangrenosum,acne, suppurative hidradenitis (PASH) and polycystic ovary syndrome: Coincidentally or aetiologically connected?

The clinical triad of pyoderma gangrenosum, acne conglobata and hidradenitis suppurativa has been named PASH syndrome. Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and inflammation. Hidradenitis suppurativa, like acne vulgaris, may be a feature of hyperandrogenism. Obesity may be associated with both hidradenitis suppurativa and PCOS. We describe a possible association between PASH syndrome and PCOS.     

PsAPASH: a rare and recent autoinflammatory syndrome associated with hidradenitis suppurativa

Hidradenitis suppurativa is a chronic inflammatory skin disease, which affects 1% of the population, being more common in young, obese and smokers, and mainly affects armpits and groin, with formation of pustules, nodules, abscesses, scars and fistulas. Recently, its association with other autoimmune diseases such as psoriasis, psoriatic arthritis, pyoderma gangrenosum, pyogenic arthritis and ulcerative colitis have been reported. These associated forms are usually resistant to standard treatment, with immunobiologicals as promising therapy. The case of a rare form of association is reported, with only one case previously described in the literature: psoriasis arthritis, pyoderma gangrenosum, acne and hidradenitis suppurativa.     

Perifolliculitis capitis abscedens et suffodiens treatment with tumor necrosis factor inhibitors: A case report and review of published cases

Perifolliculitis capitis abscedens et suffodiens (PCAS) or dissecting cellulitis is a rare condition presenting deep follicular occlusions, follicular ruptures and follicular infections in the scalp area with unknown etiology, which consequently cause primary neutrophilic cicatricial alopecia by the repeated follicular inflammation. PCAS is categorized as one of the “follicular occlusion tetrad” along with hidradenitis suppurativa, acne conglobata and pilonidal cyst. In the pathogenesis of the follicular occlusion tetrad, the involvement of neutrophils and its activator tumor necrosis factor (TNF) have been discussed. Here, we report a case of PCAS that was successfully treated with adalimumab, a human anti‐TNF monoclonal antibody. This is the first Asian case of PCAS that was improved by a TNF inhibitor.     

Perifolliculitis capitis abscedens et suffodiens successfully controlled with topical isotretinoin

Perifolliculitis capitis abscedens et suffodiens (or dissecting folliculitis of the scalp or dissecting cellulitis of the scalp or dissecting perifolliculitis of the scalp) is a rare entity and constitutes the equivalent over the scalp, of hidradenitis suppurativa and acne conglobata. Etiologic factors are unknown. Diagnosis is proven histologically. Management is very difficult and consists in systemic administration or intralesional injection of several drugs or in surgical manipulations. An 18 year-old white patient with cystic infiltrations, alopecia plaques, pustules and other inflammatory elements (clinicohistological features consistent with dissecting folliculitis of the scalp), is presented. Isotretinoin topical application assured successful control of the disease and averted the evolution of the clinical aspect to scarring alopecia and nodule formation. Topical isotretinoin exercises a curative, inhibitory and antiproliferative action, in perifolliculitis capitis abscedens et suffodiens.     

Keratitis-ichthyosis-deafness syndrome in association with follicular occlusion triad

Keratitis-Ichthyosis-Deafness syndrome is a rare congenital disorder of the ectoderm caused by mutations in the connexin-26 gene (GJB2) on chromosome 13q11-q12, giving rise to keratitis, erythrokeratoderma and neurosensory deafness. We report the case of a 31-year-old black male diagnosed as having KID syndrome. Sequencing analysis showed a heterozygous missense mutation D50N (148G > A) in the GJB2 gene. In addition to the classical features of vascularizing keratitis, erythrokeratoderma and congenital deafness, our patient presented a follicular occlusion triad with hidradenitis suppurativa (HS, alias acne inversa), acne conglobata and dissecting cellulitis of the scalp, leading to cicatricial alopecia and disfiguring, inflammatory vegetations of his scalp. Conservative therapy such as a keratolytic, rehydrating and antiseptic external therapy, antibiotic, antimycotic and retinoids were only of moderate benefit, so we finally chose the curative possibility of surgery therapy of the axillar papillomas and of the scalp. The inflammatory papillomatous regions of the axillae and of the scalp were radically debrided. Clean granulation was awaited and covered in a second session with a mesh graft from the thigh, achieving a satisfactory result. To our knowledge, only one case of KID syndrome occurring in association with follicular occlusion triad has been reported before.     

Perifolliculitis capitis abscedens et suffodiens in a caucasian: diagnostic and therapeutic challenge

Perifolliculitis capitis abscedens et suffodiens or dissecting cellulitis of the scalp is a rare, chronic destructive folliculitis of the scalp, characterized by painful nodules, purulent drainage, sinus tracts, keloid formation and cicatricial alopecia. The cause of the disease is unknown, but it is similar in many features to hidradenitis suppurativa and acne conglobata. In our case report, the patient's dermatologic appearance included one slightly erythematous, infiltrated alopecic area with draining lesions in the right parietal part of the scalp with a few alopecic areas in other parts of the scalp. The identification of the infectious agent, repeated swabs and KOH examination/or fungal cultures and tissue sampling for histopathologic analysis were necessary to confirm the diagnosis of perifolliculitis capitis abscedens et suffodiens. The patient received systemic antibiotics (azithromycin and amoxicillin-clavulanate) and oral antimycotic therapy (fluconazole), followed by a long period of oral isotretinoin with local skin care, which led to resolution and thus inhibited the evolution to scarring and nodular stage of the disease. Thus, such combined approach could be useful for other patients with these dermatologic problems.     

A case of pyoderma vegetans and the follicular occlusion triad.

A case of pyoderma vegetans (PYV) and hidradenitis suppurativa (HS) is described. Our patient had a previous history of perifolliculitis capitis abscedens et suffodiens and acne conglobata. Direct immunofluorescence findings ruled out pemphigus vegetans and suggested a potential pathogenic mechanism.     

SAPHO syndrome associated with hidradenitis suppurativa and pyoderma gangrenosum successfully treated with adalimumab and methotrexate: a case report and review of the literature

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare inflammatory condition describing the combination of skin, bone, and joint manifestations that has a heterogeneous presentation. We report a case of severe SAPHO syndrome in association with hidradenitis suppurativa and pyoderma gangrenosum in a 27‐year‐old male. The patient had an initial migratory arthritis affecting the knees, ankles, metacarpophalangeal joints, proximal interphalangeal joints, wrists, shoulder, and lower back, which progressed to a persistent arthritis and swelling at the sternum, shoulders, wrists, hands, feet, and lower back. Radiographic changes were consistent with the diagnosis of SAPHO syndrome. Serum proinflammatory cytokine levels were significantly elevated and improved substantially after 3 months of therapy. Rationale for therapy in this patient was the observation that tumor necrosis alpha antagonists have been successfully used in SAPHO syndrome, and since arthropathy was so prominent in our patient, we elected to use adalimumab combined with methotrexate.     

Pyoderma gangrenosum associated with hidradenitis suppurativa: a case report and review of the literature

Pyoderma gangrenosum is an inflammatory disease that has been found to be associated with many systemic illnesses. The case presented here is of a man with a 20-year history of hidradenitis suppurativa who developed pyoderma gangrenosum. The pyoderma lesions appeared as a single outbreak which resolved totally after immunosuppressive treatment. This association has been reported only rarely in the literature. Furthermore, in the cases reported, no relationship was apparent between the activity of both diseases. In all cases the clinical course appeared independent, with no apparent overlap in inflammatory activity or response to the drugs administered.     

Are dissecting cellulitis and hidradenitis suppurativa different diseases?

Although dissecting cellulitis (DC) and hidradenitis suppurativa (HS) are classified separately, they share many clinical, dermatoscopic, pathogenetic, and histologic aspects, as well as therapeutic options. The association between DC, HS, and acne conglobata represents the follicular occlusion triad or follicular occlusion tetrad, which may include a pilonidal sinus. DC, also known as “folliculitis et perifolliculitis capitis abscendes et suffoidens,” is classified as a secondary cicatricial and neutrophilic alopecia. It occurs with perifolliculitis of the scalp, dermal abscesses, sinus tract development, and secondary scarring alopecia. HS, sometimes known as acne inversa, is a chronic relapsing inflammatory disease afflicting apocrine gland–rich areas of the body with painful nodules and abscesses, sinus tracts, and scarring. Given the overlap between the clinical features and the pathogenesis of DC and HS, it would be more appropriate to consider these conditions as two different localizations of the same disease rather than two different pathologies, being a follicular occlusion disease occurring on the scalp and on the apocrine gland–rich areas of the body.     

Squamous cell carcinoma arising in acne conglobata

A squamous cell carcinoma was found on the back of a man who had had acne conglobata for more than forty years. Squamous cell carcinomas called Marjolin's ulcers may arise in the sites of chronic inflammation and scarring such as thermal burn scars, discoid lupus erythematosus, leg ulcerations, and foci of osteomyelitis. Squamous cell carcinoma has also been reported in all three diseases included in the so-called "follicular occlusion triad": acne conglobata, dissecting cellulitis of the scalp, and hidradenitis suppurativa.     

A case of dissecting cellulitis and a review of the literature

Dissecting cellulitis (also called perifolliculitis capitis abscedens et suffodiens) manifests with perifollicular pustules, nodules, abscesses and sinuses that evolve into scarring alopecia. It predominantly occurs in African American men between 20-40 years of age, but can occasionally affect other races and women too. Associated musculoskeletal findings are sometimes reported. When it occurs with acne conglobata, hidradenitis suppurativa, and pilonidal cysts, the syndrome is referred to as the follicular occlusion triad or tetrad. Its course is chronic and relapsing, and treatment is often difficult. Medical therapies include isotretinoin, antibiotics, and prednisone. Destructive therapies include X-ray therapy, surgical excision, and skin grafting. Laser epilation of hair follicles is a promising new therapy for dissecting cellulitis.     

Pyoderma Vegetans

BACKGROUND: Pyoderma vegetans is a rare condition that is clinically characterized by large verrucous plaques with elevated borders and multiple pustules. The etiology of this disorder remains unknown. OBJECTIVES: We describe a 24-year-old woman with rapidly evolving pyoderma vegetans. Our patient had the unique additional findings of a highly elevated serum IgE level and a history of hidradenitis suppurativa. CONCLUSIONS: Pyoderma vegetans is diagnosed on clinical and histological criteria. Differentiation must be made from disorders such as pyoderma gangrenosum, Sweet's syndrome, and deep fungal infections. We illustrate a case of pyoderma vegetans and review the literature on this rare disorder. Clinical and histological criteria for diagnosis are presented, as well as differentiation from some mimicking disorders.     

Targeting the gut‐skin axis—Probiotics as new tools for skin disorder management?

The existence of a gut‐skin axis is supported by increasing evidence, but its translational potential is not widely recognized. Studies linked inflammatory skin diseases to an imbalanced gut microbiome; hence, the modulation of the gut microbiota to improve skin condition seems to be a feasible approach. Today, there is a growing interest in natural products as alternatives to synthetic drugs. In this respect, oral probiotics could be a simple, safe and cheap modality in the therapeutic management of skin inflammation. Unfortunately, very few studies have looked into how probiotic supplementation influences inflammatory skin disorders. The result, though promising, are difficult to implement in clinical practice due to the heterogeneity of the applied supplemental regimen in the different studies. In this Viewpoint, we aim to encourage the conduction of more research in that direction to explore unambiguously the therapeutic potential of oral probiotics in dermatology. We focus on the most common inflammatory skin diseases (atopic dermatitis, psoriasis, rosacea, acne vulgaris) with an associated gut dysbiosis, but we also discuss some less common, but very serious skin pathologies (eg erythema nodosum, pyoderma gangrenosum, hidradenitis suppurativa) that are possibly linked to a disturbed gut flora composition. We dissect the possible mechanisms along the gut‐skin axis and highlight novel points where probiotics could interfere in this communication in the diseased state.     

Pyoderma gangrenosum and its syndromic forms: evidence for a link with autoinflammation

Pyoderma gangrenosum is a rare inflammatory neutrophilic dermatosis manifesting as painful ulcers with violaceous, undermined borders on the lower extremities. It may occur in the context of classic syndromes like PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) and SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis), as well as in a recently described entity named PASH (pyoderma gangrenosum, acne and suppurative hidradenitis). Pyoderma gangrenosum has recently been included within the spectrum of autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. In PAPA syndrome, different mutations involving the PSTPIP1 gene, via an increased binding affinity to pyrin, induce the assembly of inflammasomes. These are molecular platforms involved in the activation of caspase 1, a protease that cleaves inactive prointerleukin (pro‐IL)‐1β to its active isoform IL‐1β. The overproduction of IL‐1β triggers the release of a number of proinflammatory cytokines and chemokines, which are responsible for the recruitment and activation of neutrophils, leading to neutrophil‐mediated inflammation. In SAPHO syndrome, the activation of the PSTPIP2 inflammasome has been suggested to play a role in inducing the dysfunction of the innate immune system. Patients with PASH have recently been reported to present alterations of genes involved in well‐known autoinflammatory diseases, such as PSTPIP1, MEFV, NOD2 and NLRP3. Pyoderma gangrenosum and its syndromic forms can be regarded as a single clinicopathological spectrum in the context of autoinflammation.     

Dissecting cellulitis of the scalp with associated spondylarthropathy: case report and review

Arthritis is a well-recognized but uncommon accompaniment to several chronic cutaneous inflammatory conditions in which severe acne is one component. We report the case of a man with dissecting cellulitis of the scalp who developed severe peripheral and axial arthritis.     

Pyoderma gangrenosum associated with acne conglobata

We report a 16-year-old male in whom pyoderma gangrenosum appeared in conjunction with acne conglobata. The patient also developed a seronegative spondyloarthropathy that was the main presenting complaint. There was no evidence of inflammatory bowel disease. Treatment with isotretinoin was successful. Both acne and pyoderma lesions healed and the articular symptoms improved. The present case, together with other reports in the literature show that acne conglobata must be included in the list of possible associations of pyoderma gangrenosum. We also comment on acne arthritis, a relatively frequent phenomenon, although still not generally known, in acne conglobata.