Pyoderma gangrenosum in an infant: A case report and review of the literature

Pyoderma gangrenosum is a neutrophilic dermatosis that is rare in infancy, with only 20 cases reported in the literature. We present a case of infantile pyoderma gangrenosum refractory to topical steroids, tacrolimus, and dapsone as well as systemic steroids and infliximab that is currently well controlled with the addition of oral tacrolimus. To our knowledge, this is the first report of the effective, safe use of oral tacrolimus in combination with infliximab for infantile pyoderma gangrenosum. We review all current cases of infantile pyoderma gangrenosum, as well as tacrolimus and its role in the treatment of this condition.     

Dapsone 5% Gel

Dapsone, a synthetic sulfone that has been available for over 60 years, has been used to treat a myriad of cutaneous disorders. Prior to the general acceptance of isotretinoin, oral dapsone had been reported to be effective in the treatment of nodulocystic acne. However, the potential for systemic toxicity prevented its widespread adoption in the treatment of acne. For many years scientists explored the possibility of developing a topical formulation of dapsone for the treatment of acne in the hope of minimizing the adverse hematologic effects of oral dapsone. Such a formulation had been unavailable until recently. Dapsone 5% gel (Aczone?) was recently developed to treat acne vulgaris. This topical formulation was approved in the US based on two randomized, vehicle-controlled studies. A 12-month, open-label study was also conducted to assess the safety and efficacy of topical dapsone over the long term. Finally, two open-label phase I pharmacokinetic studies were conducted to evaluate the systemic absorption of topical dapsone compared with oral dapsone. This article reports the results of these studies, which show a reduction in acne lesion count comparable to those observed in clinical trials of other approved topical acne therapies. With regard to safety, the studies demonstrated that the concentrations of dapsone and N-acetyl dapsone remain low and do not accumulate over time once steady state is reached. Of the total of 50 patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency in all the studies, only two experienced a drop in hemoglobin levels, and those shifts in values were consistent with fluctuations observed for other study participants. A recent study evaluating the risk of hemolysis in patients with G6PD deficiency found topical dapsone 5% gel to be safe to use in this patient population. Based on the observations noted in the above-mentioned studies, we conclude that topical dapsone 5%gel is safe and effective in the treatment of acne vulgaris.     

An unusual presentation of a common disease

We present a case of perforating granuloma annulare (PGA), in which we show the natural history of lesions and outline the different clinical types. Our patient responded well to intralesional triamcinolone acetonide 10mg/ml injections. Although she was otherwise well, PGA can be associated with diabetes mellitus in up to 17 percent of cases. Differential clinico-histopathological diagnosis, specifically in relation to necrobiosis lipoidica diabeticorum is being discussed. Treatment for PGA is difficult; apart from topical and/or intralesional steroids (clearance up to 54% in one case series), other options include Psoralen plus UVA (PUVA), systemic isotretinoin, chloroquine or hydroxylchloroquine, sulphapyridine, dapsone, topical application of imidazole creams, and liquid nitrogen. Spontaneous remission has also been reported in up to 77 percent in one case series.     

Hailey-Hailey Disease Responding to Thalidomide

Familial benign chronic pemphigus or Hailey-Hailey disease (HHD) is a rare autosomal dominant disorder characterized by the development of recurrent blisters and erosions in the intertriginous areas. Various topical and systemic treatment options include corticosteroids, topical 5-fluorouracil, topical vitamin D analogs, topical zinc oxide, dapsone, psoralen plus ultraviolet A, systemic retinoids, cyclosporine, methotrexate, and photodynamic therapy. In recalcitrant cases, further options including, invasive methods such as grenz ray therapy, carbon dioxide laser abrasion, and erbium: YAG laser ablation, dermabrasion, electron beam therapy, botulinum toxin, and full-thickness excision of affected skin with repair by split-thickness grafting have been reported as useful in treatment of HHD. We describe a case of HHD who was treated with several treatment modalities including antibiotics, corticosteroids, and dapsone earlier and when presented to us had a severe recalcitrant disease. Thalidomide, as a modality of treatment has been successfully used in few cases earlier. Our patient responded well to thalidomide.     

Newer Approaches to the Treatment of Acne Vulgaris

The multifactorial etiology of acne vulgaris makes it challenging to treat. Current treatments include topical retinoids, benzoyl peroxide, topical and systemic antibiotics, azelaic acid, and systemic isotretinoin. Adjunctive and/or emerging approaches include topical dapsone, taurine bromamine, resveratrol, chemical peels, optical treatments, as well as complementary and alternative medications. The purpose of this paper is to discuss the therapies available for acne and their latest developments, including new treatment strategies (i.e. re-evaluation of the use of oral antibiotics and avoidance of topical antibiotic monotherapy, use of subantimicrobial antibiotic dosing, use of low-dose isotretinoin, optical treatments), new formulations (microsponges, liposomes, nanoemulsions, aerosol foams), new combinations (fixed-combination products of topical retinoids and topical antibiotics [essentially clindamycin] or benzoyl peroxide), new agents (topical dapsone, taurine bromamine, resveratrol) and their rationale and likely place in treatment. Acne vaccines, topical natural antimicrobial peptides, and lauric acid represent other promising therapies.     

Dapsone treatment of folliculitis decalvans

BACKGROUND: Folliculitis decalvans consists of recurrent patchy painful folliculitis of the scalp causing scarring alopecia. The physiopathology of this condition is still unclear, but is likely a manifestation of chronic neutrophilic bacterial folliculitis. Numerous topical and systemic treatments (corticosteroids, antistaphylococcal antibiotics) have been used with variable results. Based on the dapsone antimicrobial activity and its anti-inflammatory action especially directed to the neutrophil metabolism, we treated two patients with severe folliculitis decalvans with this drug. CASE REPORTS: The patients were treated with dapsone at a daily dose of 75 and 100 mg, respectively for 4 to 6 months. After 1 and 2 months, pustular folliculitis progressively cleared, leaving a residual non inflammatory cicatricial alopecia. When maintaining a dapsone dosage at 25 mg/day no relapse occurred during 3 years and 1 year, respectively. No important adverse effect to dapsone was evidenced. After dapsone withdrawal, a moderate relapse of the disease with pruritus and folliculitis occurred after a few weeks in both cases. The disease relapse rapidly cleared after dapsone reintroduction at a daily dose of 25 mg. COMMENTS: Dapsone at moderate dosage was well tolerated and rapidly effective in treating the two cases of folliculitis decalvans. A long term and low dose (25 mg daily) maintenance treatment avoided disease relapses.     

Linear IgA disease: complicated by alpha thalassemia

Dapsone is regarded as the treatment of choice for linear immunoglobulin A disease (chronic bullous disease of childhood). It is associated with both hemolytic anemia and methemoglobinemia. The hematotoxic effects are dose related and can result in significant hemolysis. We present a case of a patient with chronic bullous disease of childhood and alpha thalassemia trait. Complete resolution occurred on a standard dose of dapsone without significant hemolysis.     

Facial cellulitis associated with Pseudomonas aeruginosa complicating ophthalmic herpes zoster

Cellulitis is a rare and severe soft-tissue infection characterized by acute, diffuse, spreading inflammation, often associated with systemic symptoms such as malaise and fever. Surgery of the head and neck, dental infections, sinusitis, upper respiratory tract infections, and trauma are the most common portal of entry for pathogens in facial cellulitis. A very unusual case complicating an ophthalmic herpes zoster in a 74-year-old woman was observed at the department of dermatology, Cagliari University (Italy). Culture of skin swabs showed growth of numerous Gram-negative bacilli, further identified as Pseudomonas aeruginosa. Therapy with intravenous ciprofloxacin was promptly instituted on the basis of the culture and sensitivity report. She was initially treated with daily drainage and twice-daily topical fusidic acid. The lesion completely resolved in 4 weeks, and no general complications or recurrence have been observed for 6 months. Early recognition and management of facial cellulitis is mandatory to avoid serious and generalized complications. Pseudomonas aeruginosa is rarely reported in facial cellulitis; there are apparently no reports of this infection occurring as a complication of ophthalmic herpes zoster. Herpetic damage of the anatomic barrier as well as impairment of defense mechanisms because of decompensated diabetes mellitus may have facilitated the colonization and proliferation of this opportunistic pathogen in our patient.     

Pentoxyfilline as a treatment for subcorneal pustular dermatosis

Subcorneal pustular dermatosis (SPD) is a rare pustular neutrophilic dermatosis in which groups of sterile pustules appear in the superficial (subcorneal) skin. This chronic condition can be associated with significant morbidity and decreased quality of life. Dapsone is the first‐line therapy for SPD, but some patients fail to respond or cannot tolerate it. In these instances, patients may be treated with second‐line therapies such as phototherapy, topical corticosteroids, or systemic agents including glucocorticoids, acitretin, immunosuppressive, or biologic medications. These therapies may not always be efficacious and can be associated with intolerable adverse effects. Here, we report a case of a patient who sustained long‐term remission and no side effects with the novel use of pentoxifylline, a tumor necrosis factor‐alpha inhibitor, as monotherapy. Pentoxifylline should be considered as a possible therapy in patients with SPD intolerant to dapsone.     

Epidermolysis bullosa acquisita in childhood

This case report of an 11-year-old girl describes a juvenile form of epidermolysis bullosa acquisita, an autoimmune disease of IgG antibodies to basement membrane type 7 collagen. Our case illustrates an unusually severe, acute inflammatory presentation of this condition with prominent mucosal and constitutional features requiring admission to a paediatric burns unit. The treatment consisted of supportive topical and systemic agents, prednisolone and dapsone. She responded to dapsone alone and the course of the illness was uneventful.     

Low‐dose naltrexone: a novel treatment for Hailey–Hailey disease

Hailey–Hailey disease (chronic benign familial pemphigus) is a rare inherited dermatosis typically characterized by erosions at intertriginous sites preceded by minor trauma or stress. We report a case of treatment‐resistant Hailey–Hailey disease having failed topical and oral steroids, prophylactic aciclovir and doxycycline, and systemic therapies including dapsone, acitretin and ciclosporin. Low‐dose naltrexone 4·5 mg once daily was commenced following an incidental benefit in this patient's similarly affected sister. The clinical and psychological response to date has been considerable.     

Spotlight on topical pimecrolimus in atopic dermatitis

Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is a nonsteroid, has anti-inflammatory activity, and has demonstrated efficacy in reducing symptoms of atopic dermatitis in adult and pediatric patients when applied topically. Compared with vehicle, topical pimecrolimus 1.0% cream was significantly more effective at reducing symptoms of atopic dermatitis, as measured by the Eczema Area and Severity Index (EASI), in infants aged 3 to 23 months, children aged 2 to 17 years, and adults. The median reductions from baseline in the total EASI score in adults after treatment with pimecrolimus 1.0% or corresponding vehicle twice daily for 3 weeks were 47 and 0%, respectively. In infants and children, treatment with pimecrolimus 1.0% twice daily for 6 weeks resulted in significant decreases in mean EASI scores compared with vehicle. The severity of pruritus was significantly reduced in patients of all age groups after topical treatment with pimecrolimus 1.0% cream. Compared with vehicle, the incidence of eczematous flares was also reduced by intermittent long-term use of topical pimecrolimus 1.0% in adults, children and infants. Sixty-one percent of children treated with pimecrolimus for 1 year completed the first 6 months of treatment without experiencing a flare, compared with 35% of patients who received vehicle. Furthermore, the use of topical corticosteroids for the treatment of uncontrolled flares in adults, children and infants was lower in the pimecrolimus groups than in the vehicle groups. Topical pimecrolimus 1.0% cream is well tolerated in atopic dermatitis patients of all age groups. There were no clinically relevant systemic adverse events reported from any of the studies in patients with atopic dermatitis. The most frequently reported adverse events pertained to application site reactions, such as burning and a feeling of warmth. In conclusion, topical pimecrolimus 1.0% cream has shown efficacy in the treatment of mild to moderate atopic dermatitis in infants, children and adults. Although tolerability data concerning infants and children have not yet been published in full, the drug appears to be well tolerated in all age groups, and there have been no reports of clinically relevant systemic adverse events. Furthermore, pimecrolimus has shown no potential for skin atrophy, a problem commonly associated with treatment with topical corticosteroids. Topical pimecrolimus 1.0% provides a promising and well tolerated treatment option in the management of infants, children and adults with mild to moderate atopic dermatitis.     

Efficacy of topical tacrolimus for treating the malar rash of systemic lupus erythematosus

The rash of systemic lupus erythematosus (SLE) is usually treated with topical corticosteroids, but prolonged use causes adverse cutaneous side-effects. We assessed the efficacy of topical tacrolimus for treating the skin lesions of SLE. Three patients with SLE affecting their facial skin applied 0.1% tacrolimus ointment on one side of their face twice daily for 3 weeks, in conjunction with a sunscreen cream. After 3 weeks, erythema on the treated side was ameliorated in all three patients compared with the untreated side. Although the study is preliminary, the results demonstrate that topical tacrolimus may be useful for treating the malar rash of SLE.     

Acantholytic pityriasis rubra pilaris associated with topical use of imiquimod 5%: case report and literature review

Topical use of immune response modifiers, such as imiquimod, has increased in dermatology. Although its topical use is well tolerated, it may be associated with exacerbations of generalized cutaneous inflammatory diseases, possibly through the systemic circulation of pro-inflammatory cytokines. This report describes a case of development of pityriasis rubra pilaris, a rare erythematous-papulosquamous dermatosis, in a woman aged 60 years during treatment with imiquimod 5% cream for actinic keratosis. It evolved with erythrodermic conditions and palmoplantar keratoderma, presenting progressive clinical resolution after the introduction of methotrexate. The authors emphasize the importance of recognizing possible systemic reactions associated with the topical use of imiquimod.     

Treatment of eosinophilic cellulitis (Wells syndrome) – a systematic review

Eosinophilic cellulitis (Wells syndrome) is a rare inflammatory skin disease defined by erythematous, tender, sometimes urticarial plaques, possibly with vesicles and bullae, and granulomatous eosinophilic infiltrates in the dermis. Usually the disease has a benign course with spontaneous remission within a few weeks. Nevertheless, recurrences are quite frequent and may occur for several years. The objective of this study was to review the so far reported treatment options for Wells syndrome in a systematic manner. This systematic review is based on a search on Medline, Embase and Cochrane Central Register for English and German articles from 1970 to 2015. Advices on the treatment of Wells syndrome are limited predominately to case reports or to small case series. There are no randomized controlled trials, and control groups are missing. A variety of treatment options for Wells syndrome were reported including topical and systemic corticosteroids, antihistamines, cyclosporine, dapsone, azathioprine, griseofulvin, doxycycline, minocycline, antimalarial medications, oral tacrolimus/topical tacrolimus, sulfasalazine, interferon alpha and gamma, TNF alpha inhibitors, colchicine and PUVA therapy. As well‐designed, randomized controlled trials are missing, no guidelines for the treatment of this disease can be given. Due to the small number of patients and the frequent misdiagnosis of this clinical entity, the aim of this systematic overview is to call attention to this rare condition and to help clinicians to diagnose and treat Wells syndrome effectively. Due to the good prognosis and tendency to resolve, systemic treatment should be limited to cases resistant to local therapy or with widespread lesions.     

Dapsone

Dapsone and other sulfonamides have been used successfully in the treatment of patients with a variety of blistering skin diseases. The patients most likely to respond to dapsone therapy have a predominantly neutrophilic infiltrate in their skin. Therefore the blistering diseases with the most consistent responses to dapsone therapy include dermatitis herpetiformis and linear IgA disease. Dapsone's precise mechanism of action is unknown. In vitro studies have shown that dapsone can interfere with the production of and response to neutrophil chemoattractants and that it may impair the neutrophils' ability to localize to sites of inflammation and produce toxic oxygen intermediates. The safe use of dapsone requires an understanding of the pharmacology and adverse effects of the drug. Hemolytic anemia and methemoglobinemia are two of the dose-related adverse effects. Agranulocytosis, motor neuropathy, and dapsone hypersensitivity syndrome are some of the severe idiosyncratic effects that can occur in patients treated with dapsone. Dapsone is an effective drug for the management of patients with some blistering disease, especially those with predominant neutrophilic infiltrates in the skin. Careful patient selection and close monitoring of patients during therapy with dapsone are critical elements in the safe and effective use of dapsone for patients with blistering skin diseases.     

Erosive pustular dermatosis of the scalp: causes and treatments

Erosive pustular dermatosis of the scalp is a rare condition which primarily affects older women after local trauma and has historically been treated with topical steroids. As it is a rare entity and resembles other dermatologic conditions, it may easily be misdiagnosed. Identifying the causes and evaluating the efficacy of treatments of erosive pustular dermatosis of the scalp (EPDS) is of great importance to both avoid misdiagnosis and ensure optimal treatment of this rare condition. There are numerous causes. In addition to surgeries and physical injuries, topical and procedural treatments for actinic keratoses and androgenetic alopecia can trigger the development of lesions. There are also documented associations with several autoimmune and systemic conditions. Besides corticosteroids, topical tacrolimus and photodynamic therapy were the most commonly used treatments for EPDS. They were effective with few recurrences and adverse effects. Other successful treatment options were topical dapsone, silicone gels, calcipotriol, acitretin, and isotretinoin. Oral dapsone can be used in cases of disseminated disease. Zinc sulfate should be considered with low‐serum zinc levels. While cyclosporine was effective, there were adverse effects that may limit its use. It is important for dermatologists to be aware of the wide array of potential causes of erosive pustular dermatosis and include it on their differential. Additionally, although high‐potency topical steroids have been historically used as the first‐line treatment, there are many other effective treatments that may avoid recurrence and skin atrophy, particularly in the elderly population.     

Lupus miliaris disseminatus faciei: A resistant case with response to cyclosporine

Lupus miliaris disseminatus faciei (LMDF) is a chronic, inflammatory dermatosis of unknown etiology, characterized by multiple, monomorphic, symmetrical, reddish‐brown papules over forehead, cheeks, and eyelids. Histopathology shows perifollicular epitheloid cell granuloma. Though numerous therapies, ranging from cyclines, macrolides, dapsone tranilast, isotretinoin, steroids, and tacrolimus have been tried, the results are inconsistent, except with systemic steroids. One approach is to administer therapies based on the histological findings and the corresponding mode of action of drugs, thus antibiotics and dapsone are effective in the early inflammatory stage while clofazamine can be used in the granulomatous stage of the disease. A case of LMDF, recalcitrant to multiple systemic therapies, who responded dramatically to cyclosporine (50 mg twice daily), which probably was due to the specific effect on T_H1 cell response which mediates cell mediated immunity responsible for granulomatous changes on histology has been reported. This case highlights that LMDF is an independent granulomatous entity (not a variant of rosacea or tuberculosis).     

Treatment of bullous pemphigoid with dapsone, methylprednisolone, and topical clobetasol propionate: a retrospective study of 62 cases

Dapsone has been used successfully as adjuvant therapy for bullous pemphigoid (BP). The effectiveness of dapsone for this indication, however, remains controversial. We evaluated the effectiveness and adverse events of dapsone (1.0-1.5 mg/kg per day) in combination with oral methylprednisolone (tapering doses of 0.5 mg/kg per day) and topical clobetasol propionate (initially applied once daily on lesions only) in the treatment of BP. Sixty-two patients treated with this regimen were analyzed retrospectively. Patients were free of new blisters after a mean (+/- SD) of 22 +/- 13 days (median, 20 days). After 3 and 6 months of treatment, methylprednisolone could be reduced to less than 10 mg/d in 71% and 91% of patients, respectively; after 12 months of treatment, 53% of patients were in complete remission without receiving further therapy. Dapsone-related side effects were usually mild except in 3 patients (5%), 2 patients with anemia (hemoglobin level, <7 g/dL) and 1 with agranulocytosis. Our data suggest that dapsone used in combination with systemic and topical corticosteroids may be a relatively safe and effective treatment option for BP.