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.     

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.     

Concurrent Hidradenitis Suppurativa,Inflammatory Acne,Dissecting Cellulitis of the Scalp,and Pyoderma Gangrenosum in a 16‐Year‐Old Boy

We report the case of a 16‐year‐old boy who presented to our clinic with concomitant hidradenitis suppurativa, inflammatory acne, dissecting cellulitis of the scalp, and pyoderma gangrenosum. Recent reports describe the co‐occurrence of pyoderma gangrenosum, acne, and hidradenitis suppurativa. This case further expands the spectrum of concomitant pyoderma gangrenosum and dissecting cellulitis of the scalp.     

Pyoderma gangrenosum associated with ulcerative colitis and subcutaneous and splenic abscesses

Pyoderma gangrenosum is a rare, chronic, inflammatory ulcerative skin disease of unknown etiology and pathogenesis. It is often associated with systemic disease. We describe a patient with pyoderma gangrenosum associated with ulcerative colitis and aseptic abscesses of the subcutis and spleen, which have been rarely reported previously. These manifestations were cleared by combined therapy with minocycline hydrochloride and diaphenylsulfone.     

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.     

A new type of minocycline-induced cutaneous hyperpigmentation

Pigmentary disorders are recognized adverse effects of the semi-synthetic tetracycline derivative antibiotic, minocycline. Three distinct types of minocycline-induced cutaneous pigmentation have been described. Type I, blue-black pigmentation confined to sites of scarring or inflammation on the face; Type II, blue-grey circumscribed pigmentation of normal skin of the lower legs and forearms; and Type III, diffuse muddy brown pigmentation of normal skin accentuated in sun-exposed areas. We report two patients with acne vulgaris with a fourth type of minocycline-induced cutaneous pigmentation. They presented with circumscribed blue-grey pigmentation within acne scars confined to the back. Histology showed pigment within dendritic cells, and extracellularly throughout the dermis. Histochemistry identified a calcium containing melanin-like substance. Iron was absent. Immunohistochemistry confirmed some pigment-containing cells to be macrophages. Electron microscopy demonstrated electron-dense granules, free and membrane-bound, within macrophages and fibroblast-like cells. Energy-dispersive X-ray analysis confirmed the presence of calcium. Iron was absent. This fourth type of cutaneous minocycline hyperpigmentation may be a variant of Type I, but based on clinical, pathological and microanalytical differences, appears to be a new entity. The pigment may be a drug metabolite-protein complex chelated with calcium, or an insoluble minocycline-melanin complex. We propose a classification of cutaneous minocycline pigmentation based on clinico-pathological criteria.     

Acute Form of Pyoderma Gangrenosum Induced by Traumatic Injury

A 45-year-old man with the acute form of pyoderma gangrenosum is reported. He developed characteristic ulcers that rapidly followed violaceous erythema at sites of traumatic injury. The skin lesions repeatedly appeared six times within 7 years. Each time, the skin lesions were localized to sites of trauma, and no systemic symptoms nor abnormal laboratory findings were associated. Histological findings were acute superficial inflammation with neutrophilic infiltration into the dermis. Sweet's syndrome-like skin lesions were once associated, indicating that pyoderma gangrenosum and Sweet's syndrome have a close relationship. Nonsteroidal antiinflammatory drugs, potassium iodide, and minocycline were not effective. He was successfully treated with oral administration of corticosteroid. The pathergy of this patient must have been caused not only by the trauma itself but by additional factors such as epidermal components or contaminating micro-organisms, since traumatic injury did not always cause the skin lesions.     

Minocycline-induced hyperpigmentation in patients with pemphigus and pemphigoid

BACKGROUND: Immunosuppressive medications typically used to treat the immunobullous disorders pemphigus vulgaris, pemphigus foliaceous, and bullous pemphigoid can have serious adverse effects. The tetracycline family of antibiotic drugs has been shown to be effective in the treatment of these conditions with a more favorable side effect profile. Minocycline hydrochloride use has been associated with various forms of hyperpigmentation, and its incidence is well reported in acne vulgaris and rheumatoid arthritis. We examined a series of 9 patients treated with minocycline for pemphigus or pemphigoid, most of whom have developed cutaneous hyperpigmentation. OBSERVATIONS: Seven of 9 patients treated with minocycline, 50 mg daily (1 patient) or 100 mg twice daily (8 patients), for pemphigus vulgaris, pemphigus foliaceous, or bullous pemphigoid developed hyperpigmentation, which necessitated discontinuing therapy. Five of these patients had experienced notable clinical improvement of their immunobullous disease with minocycline therapy. The average duration of treatment was 8.2 months (range, 1-25 months). The second most common adverse effect in our group was oral candidiasis, which occurred in 2 patients. CONCLUSIONS: We found a favorable response to minocycline therapy in 5 of 9 patients. However, 7 patients developed localized hyperpigmentation as early as 1 month after starting medication use. This incidence of minocycline-induced hyperpigmentation is significantly higher in immunobullous disease than in acne vulgaris or rheumatoid arthritis. This increased incidence may be related to an increase in pigment deposition complexed with collagen during the remodeling process, subclinical inflammation, or glucocorticosteroid-induced skin fragility. The hyperpigmentation process was reversible, as most of our patients had fading of their pigmentation after minocycline cessation.     

Minocycline-induced pigmentation occurring in two sisters

Two sisters are described who developed facial pigmentation while on minocycline therapy for acne vulgaris. It is suggested that the possible mechanisms for this relatively uncommon complication occurring in these two patients may be due to either a genetically acquired alteration in metabolic handling of minocycline or to the ethinyloestradiol component of Dianette, which they were also receiving as treatment for their acne vulgaris. It is concluded that patients on minocycline should be regularly screened for signs of hyperpigmentation, especially if they are on other drugs which are known to accentuate pigmentation of skin.     

Targeted treatment of pyoderma gangrenosum in PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome with the recombinant human interleukin-1 receptor antagonist anakinra

The triad of sterile pyogenic arthritis, pyoderma gangrenosum and acne is known by the acronym of PAPA syndrome. It is a rare autosomal dominant disease of early onset. The treatment of pyoderma gangrenosum is challenging as there is often only partial response to systemic glucocorticosteroids and immunosuppressive therapies. We report the rapid and lasting response of pyoderma gangrenosum to the targeted treatment with the recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) anakinra in a patient with PAPA syndrome.     

Combination of microneedling and glycolic acid peels for the treatment of acne scars in dark skin

Introduction Acne scars can cause emotional and psychosocial disturbance to the patient. Various modalities have been used for the treatment of acne scars like punch excision, subcision, peels, microdermabrasion, unfractionated and fractioned lasers. The latest in the treatment armamentarium is microneedling. Acne scars commonly coexist with postinflammatory hyperpigmentation. A combination of microneedling and glycolic acid (GA) peels was found to give excellent results in the treatment of such scars. The aim was to study the efficacy of a combination of microneedling with glycolic peel for the treatment of acne scars in pigmented skin. Method Thirty patients in the age group of 20–40 years with atrophic box type or rolling scars with postinflammatory hyperpigmentation were chosen for the study. Two groups were made. The first group comprised of 30 patients in whom only microneedling was performed once in 6 weeks for five sessions. In the second group of 30 patients, a combination of microneedling and 35% GA peels was carried out. Patients from both groups were evaluated on the basis of Echelle d’Evaluation clinique des Cicatrices d’acné classification. Results Based on the objective scoring and its statistical analysis, there was significant improvement in superficial and moderately deep scars (grade 1–3). There was also improvement in skin texture, reduction in postacne pigmentation in the second group. Conclusion Microneedling is a simple, inexpensive office procedure with no downtime. It is safe in Indian skin (skin types III–IV). The combined sequential treatment with GA peel caused a significant improvement in the acne scars without increasing morbidity.     

Wegener's granulomatosis presenting as pyoderma gangrenosum

This case report illustrates that pyoderma gangrenosum may be the only presenting feature of Wegener's granulomatosis. The pyoderma gangrenosum lesions were in this case effectively treated by minocycline hydrochloride but this did not prevent the later manifestations of Wegener's granulomatosis from developing.     

Dramatic improvement of pyoderma gangrenosum with infliximab in a patient with PAPA syndrome

Infliximab, a chimeric antitumor necrosis factor alpha monoclonal antibody (anti-TNF alpha), has been recently shown to have a beneficial effect on pyoderma gangrenosum associated with inflammatory bowel disease. Patients with the syndromic triad of pyogenic sterile arthritis, pyoderma gangrenosum, and acne, an autoinflammatory process caused by mutations in the CD2 binding protein-1 (CD2BP1) gene, can have severe pyoderma gangrenosum. We describe a 14-year-old patient with this syndrome who was unresponsive to multiple therapies. A dramatic improvement in his pyoderma gangrenosum was observed after one infusion of infliximab, and a second infusion led to its resolution. Our observation extends the therapeutic use of infliximab to this component of PAPA syndrome.     

Clinical trial of a laser device called fractional photothermolysis system for acne scars

Ablative laser resurfacing is an effective treatment for acne scars. However, edema and prolonged erythema are common. Additionally, scarring and hyperpigmentation are often induced. A new concept of laser called fractional photothermolysis has been designed to create microscopic thermal wounds to achieve skin rejuvenation without significant side-effects. We treated 10 patients with acne scars using this laser system (Reliant Fraxel SR Laser). All the patients were successfully treated with minimal adverse effects. The fractional photothermolysis system represents an optional method for the treatment of acne scars.     

Clinical Management of Pyoderma Gangrenosum

Pyoderma gangrenosum is a noninfectious neutrophilic dermatosis that usually starts with sterile pustules which rapidly progress to painful ulcers of variable depth and size with undermined violaceous borders. In 17 to 74% of cases, pyoderma gangrenosum is associated with an underlying disease, most commonly inflammatory bowel disease, rheumatological or hematological disease or malignancy. Diagnosis of pyoderma gangrenosum is based on a history of an underlying disease, typical clinical presentation and histopathology, and exclusion of other diseases that would lead to a similar appearance. Randomized, double-blinded prospective multicenter trials investigating the treatment of pyoderma gangrenosum are not available. The treatments with the best clinical evidence are systemic corticosteroids (in the initial phase usually 100 to 200 mg/day) and cyclosporine (mainly as a maintenance treatment). Combinations of corticosteroids with cytotoxic drugs such as azathioprine, cyclophosphamide or chlorambucil are used in patients with disease that is resistant to corticosteroids. The combination of corticosteroids with sulfa drugs, such as dapsone, or clofazimine, minocycline and thalidomide, has been used as a corticosteroid-sparing alternative. Limited experience has been documented with methotrexate, colchicine, nicotine, and mycophenolate mofetil, among other drugs. Alternative treatments include local application of granulocyte-macrophage colony-stimulating factor, intravenous immunoglobulins and plasmapheresis. Skin transplants (split-skin grafts or autologous keratinocyte grafts) and the application of bioengineered skin is useful in selected cases in conjunction with immunosuppression. Topical therapy with modern wound dressings is useful to minimize pain and the high risk of secondary infection. The application of topical antibacterials cannot be recommended because of their potential to sensitize and their questionable efficacy, but systemic antibacterial therapy is mandatory when infection is present. Despite recent advances in therapy, the prognosis of pyoderma gangrenosum remains unpredictable.     

Superficial granulomatous pyoderma: a localized vegetative form of pyoderma gangrenosum

Twenty-five patients had superficial ulcerative and vegetative pyoderma with granulomatous histologic findings. Healing occurred without systemic corticosteroid therapy in all but three patients. All patients had clinical pyoderma gangrenosum. In five patients the lesion occurred after surgery of the skin. Histopathologic study of 40 biopsy specimens showed focal neutrophilic abscesses of the papillary dermis, often with peripheral palisading histiocytes and foreign-body giant cells. Pseudoepitheliomatous, vegetative hyperplasia and sinus tract formation were observed frequently. All patient had massive areas of plasmacytosis, and 13 had eosinophils. Granulation tissue, hemorrhage, and fibrosis were additional features in some areas. Foreign material in the lesions was considered unimportant, except in one patient with a starch granuloma. Therapy with local corticosteroids, minocycline, tetracycline, or sulfa drugs resulted in healing in 15 patients. We believe that we have identified a localized, limited form of chronic superficial pyoderma gangrenosum with verrucous and ulcerative lesions and a granulomatous histologic appearance that represents a unique pattern of this disease in some patients.     

A cross‐sectional,multi‐center study on treatment of facial acne scars with low‐energy double‐pass 1450‐nm diode laser

Acne scars are the ultimate outcome of acne vulgaris, a prevalent skin disorder affecting the pilo‐sebaceous unit. Laser resurfacing has been demonstrated to be an efficient therapy option for acne scars. Hence, we adopted this concept and conducted a study to evaluate the safety and efficacy of low‐energy double‐pass 1450‐nm diode laser on acne scars. This study was conducted on 48 patients with acne scars, treated at 4‐week interval with low‐energy double‐pass 1450‐nm diode laser. Patients were evaluated clinically and with photographs, at day 0, first month and third month post the final treatment and during follow‐up visit. Five treatment sessions were completed by all patients. Approximately, 79.2% of patients showed around 30% improvement. At the end of third month follow‐up, 92.9% of the patients demonstrated >30% improvement. Vesicle formation was observed in two cases, with no post‐inflammatory hyperpigmentation and transient hyperpigmentation was observed in one case, which vanished within 2 months. Our study showed that 1450‐nm diode laser treatment was efficient and well endured in facial acne scars when used with double‐pass at low‐energy.     

Pyoderma gangrenosum or cutaneous lymphoma: a difficult clinical diagnosis

Pyoderma gangrenosum is frequently associated with an underlying condition such as ulcerative colitis or a myeloproliferative syndrome. However, lymphoproliferative malignancies have only rarely been seen concurrently with pyoderma gangrenosum. We present the case of a patient with small lymphocytic lymphoma who noted a slowly enlarging skin ulcer that was clinically consistent with pyoderma gangrenosum. Examination of a biopsy specimen showed infiltration of the skin with lymphoma cells as well as deeper necrotic material and thrombosis of vessels that were infiltrated by lymphoma. This case illustrates the difficulty of differentiating pyoderma gangrenosum from cutaneous lymphoma clinically.     

Evaluation of CROSS technique with 100% TCA in the management of ice pick acne scars in darker skin types

Background Acne scars are difficult to treat. Chemical reconstruction of skin scars (CROSS) is a technique using high strength trichloroacetic acid (TCA) focally on the atrophic acne scars to induce collagenization and cosmetic improvement. Objective The aim of this study was to evaluate the efficacy and safety of CROSS technique using 100% TCA in ice pick scars in dark skin types IV and V. Methods Thirty patients with ice pick acne scars were initially primed for 2 weeks before the procedure. The priming agents used were hydroquinone 4% applied in the morning and tretinoin 0.025% in the night. Sunscreens were advised to prevent postinflammatory hyperpigmentation. Subsequently, they underwent focal application of 100% TCA with a wooden toothpick in each individual scar, at 2 weekly intervals, for four sessions. Improvement was assessed by the physician, photographic assessment by an independent investigator, and patient feedback by visual analogue scale after the fourth treatment. Results Excellent improvement (more than 70%) was observed in the majority of patients (73.3%), while 20% patients showed good improvement (50–70%) and 6.7% patients had fair results (30–49%) at the end of four sessions. Transient hypopigmentation was observed in one patient and hyperpigmentation in two patients. However, no significant adverse effects such as prolonged pigmentary changes or scarring were noted. Conclusion Treatment of ice pick acne scars with the CROSS technique using high strength 100% TCA is a safe, minimally invasive, efficacious, and cost‐effective technique in darker skin. Adequate priming and continued use of hydroquinone and tretinoin reduces complications and promotes healing.     

Tetracycline/doxycycline-induced cutaneous depressed pigmentation

Pigmentary disorders are recognized adverse effects of tetracyclines. Unlike minocycline, which occasionally causes black pigmentation of a variety of tissues, tetracycline itself or doxycycline is rarely attributed to the pigmentation of skin. Herein, we report the first case report of blue-black discoloration developed within depressed acne scars following tetracycline/doxycycline therapy for acne.