Malignant Melanoma Developing in an Area of Palmoplantar Keratoderma (Greither's Disease)

We report a case of malignant melanoma arising on the hyperkeratotic sole of a patient with palmoplantar keratoderma (PPK). Hyperkeratotic lesions were also seen on the dorsa of both hands and feet and the extensor aspects of elbows and knees. The patient's PPK appeared to have been transmitted by an autosomal dominant gene. Histologically, the hyperkeratotic lesions showed acanthosis, marked hyperkeratosis without parakeratosis, and hypergranulosis. All the findings corresponded to those of Greither's disease with malignant melanoma.     

Cutaneous bullae following acute steroid withdrawal in systemic lupus erythematosus

A patient with systemic lupus erythematosus developed severe widespread bullae following sudden steroid withdrawal. Histologically the lesion was suggestive of leukocytoclastic vasculitis with a regenerating subepidermal bulla, but immunofluorescence on non-lesional skin was typical of lupus erythematosus. Treatment led to resolution of the bullous eruption, and despite exacerbations of the patient's lupus nephropathy, the blisters have not recurred. The differential diagnosis of bullous LE is discussed.     

Punctate porokeratotic keratoderma—its occurrence with internal neoplasia

Punctate porokeratotic keratoderma (PPK) represents a diffuse involvement of palms and soles by multiple, acuminate keratotic papules and plugs, histologically identified by parakeratotic cornoid lamellae. A possible association between PPK and internal malignancy has been previously noted by Herman in 1973². A patient with a 3-month history of PPK is described in which a bronchial carcinoma was recently diagnosed. This association led us to speculate that PPK could be a sign of internal neoplasia, as already established for other forms of palmoplantar keratoderma. We suggest that the presence of an underlying malignancy must be screened for when a diagnosis of PPK is proposed.     

HLA‐DRB1*04:05 in two cases of Vogt–Koyanagi–Harada disease‐like uveitis developing from an advanced melanoma patient treated by sequential administration of nivolumab and dabrafenib/trametinib therapy

Although uveitis is reported as a rare adverse event (AE) associated with dabrafenib/trametinib therapy or nivolumab, the occurrence of severe uveitis is extremely rare. We describe two cases of Vogt–Koyanagi–Harada (VKH)‐like uveitis developing after the sequential administration of nivolumab and dabrafenib/trametinib therapy. Interestingly, both cases had HLA‐DRB1*04:05, which is strongly associated with VKH disease, and achieved biologically complete remission after the treatment for uveitis. Our cases suggest a possible correlation between VKH‐like uveitis as an AE and the clinical outcomes of sequential administration of nivolumab and dabrafenib/trametinib therapy for the treatment of advanced melanoma.     

Practical compendium for psoriasis management

Psoriasis management is complex and challenging. It should be tailored for each patient. Treatment strategy differs according to patient's age, sex, disease type, disease severity, burden on patient's quality of life, comorbidities, involvement of specific sites, and pregnancy. The choice of the appropriate therapeutic must take into consideration the availability, the price, and the patient's preferences. It is very important that the chosen treatment is not more unpleasant, intolerable, or dangerous than the disease itself. According to the disease type, severity, and effect on patient's quality of life, dermatologist chooses whether to start with topical therapy, phototherapy or systemic therapy, or a combination of two or more of them. Under each category, there are different types of therapies that can be the first line therapeutics, second line, or even contraindicated. In this compendium, we provide dermatologists with different treatment plans considering all the mentioned variables so that a dermatologist can choose the optimum plan for the patient.     

Post‐erysipela panniculitis ossificans of the lower leg treated with pentoxifylline

We report the case of a female patient who developed a firm, wooden‐like, nonpitting edema of the left lower leg after a dermo‐hypodermitis. The clinical picture was accompanied by intense pain, strongly impacting the patient's quality of life. A soft‐tissue ultrasound demonstrated several millimetric hyperechoic linear lesions whose histopathological examination was conclusive for panniculitis ossificans. A conservative medical management with compression stockings associated with pentoxifylline 800 mg/day was prescribed with improvement of the edema and, in particular, a good pain control. To date, after a 2‐year therapy with pentoxifylline, the leg wooden‐like edema has substantially improved, despite the persistence of the well‐known foci of ossification, and the pain has resolved, conditioning a substantial improvement of the patient's quality of life. No side effect has been observed during the routine follow up. Although there is no unanimous opinion in the literature about the effect of pentoxifylline on bone formation and osteogenic differentiation, pentoxifylline treatment proved to be beneficial in our patient both for the heterotopic ossification process and the pain control. We collected some of the data in literature about pentoxifylline effects and advanced some hypotheses to explain our results. Finally, we suggest that an anti‐inflammatory and vasodilators drug such as pentoxifylline could be a possible alternative in heterotopic ossification disorders.     

Adjuvant therapy for cutaneous melanoma: a systematic review and network meta-analysis of new therapies

New drugs have been recently approved as adjuvant therapies for melanoma. In this Bayesian network meta-analysis, we aimed to assess the best therapeutic option in terms of recurrence-free survival (RFS), overall survival (OS) and adverse events (AEs). PubMed, Embase, Cochrane library and the American Society of Clinical Oncology databases were searched from inception until 20 August 2018. We estimated adjusted hazard ratios (HRs) for RFS and OS and relative odds ratios (ORs) for AEs and surface under the cumulative ranking (SUCRA) probabilities were calculated. A number of 872 records were identified, and six were finally included in the meta-analysis. A total of 4244 patients in six studies were randomized. The following therapies were considered in the selected studies: combined dabrafenib and trametinib, vemurafenib, nivolumab, ipilimumab and pembrolizumab. Nivolumab demonstrated the highest probability (75.1%) of being the best in term of RFS, followed by dabrafenib+trametinib, pembrolizumab, ipilimumab and vemurafenib; however, OS was not estimable. Concerning AEs, pembrolizumab and nivolumab showed the highest probability to be less associated with any and 3–4 grade AEs (83.1% and 64.4%, respectively). In conclusion, all new drugs are highly effective in adjuvant setting, and the best choice is dependent of patient's context.     

Multiple skin cancers in patients with mycosis fungoides after long‐term ultraviolet phototherapy

Phototherapy is a useful noninvasive therapy, but it can induce cutaneous malignant tumours, including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). We report on a 79‐year‐old man who had long‐standing mycosis fungoides for 40 years, which had been treated with psoralen ultraviolet A therapy for 37 years at a dose of approximately 5000 J/cm². Approximately 6 years before presentation, numerous types of cutaneous malignancies, including actinic keratosis, BCC and SCC, had begun to develop all over the patient's body. We hypothesized that he was experiencing a pathogenesis similar to patients with xeroderma pigmentosum (XP), and we therefore assessed his DNA repair capacity. Based on these investigations, the patient was eventually diagnosed as non‐XP, even though we detected that his DNA repair capacity was slightly lower than that of normal controls, which may have led to the skin cancers. We speculate that multiple skin malignancies can be induced by long‐term phototherapy in patients with slightly impaired DNA repair capacity.     

Combination of an EGFR blocker and a COX‐2 inhibitor for the treatment of advanced cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers worldwide. Epidermal growth factor receptor (EGFR) is expressed at the cell surface by more than 90% of SCCs and its activation is responsible for cell cycle progression, proliferation, survival, angiogenesis and metastasis. Cyclooxygenase‐2 (COX‐2) is an enzyme up‐regulated through EGFR signaling and responsible for some of the EGFR‐dependent biological effects. An 88‐year‐old man presented with a recurrent, locoregionally meta‐static SCC of the right parietal region, which was resistant to radiotherapy. With a combination therapy of an EGFR blocker (cetuximab) and a COX‐2 inhibitor (celecoxib), the tumor regressed partially and the patient's Karnofsky index improved. We speculate that the combined use of cetuxi‐mab and COX‐2 inhibitors can be a new and effective therapy for advanced and recurrent cutaneous SCCs.     

Psoriasis improvement after gastric bandage in a patient partial responder to infliximab

Patients overweight or obese have more severe psoriasis than normal weight patients. Sometimes the excessive weight is related to a lack of efficacy of systemic treatment. We report a case of a psoriatic patient that experienced a dramatic improvement of psoriasis after weight loss surgery by gastric bandage. The great weight loss was accompanied by an effectiveness gain of response to infliximab. The mechanism responsible for this association is not certain, but it is probably multifactorial, involving genetic, environmental and immune‐mediated factors. It has been suggested that adipose tissue can dramatically alter the volume of drug distribution and limit drug efficacy. Moreover, a reduction of weight could favour the response to therapy and remission of the disease, inducing an improvement in patient's quality of life. Gastric bandage has a scarce rate of complications, a fast recovery and scarce life‐threatening complications. It should be considered in obese patient that not shown effectiveness to therapy.     

Intravenous Immunoglobulin Treatment in a Child with Resistant Atopic Dermatitis

In a subgroup of patients suffering from atopic dermatitis (AD), treatment is quite difficult even after taking oral immunosuppressants. High-dose intravenous immunoglobulin (IVIG) treatment has been reported to be beneficial for them in a few uncontrolled trials. Herein we report a case of intractable AD in a 5-year-old girl who had significant clinical improvement after receiving 3 cycles of IVIG treatment (2 g/kg) without notable side effects. Since the first infusion of IVIG, the patient''s skin lesions improved steadily and the improvement persisted until the 8-month follow-up. The eczema area and severity index score decreased remarkably, while immunologic parameters did not correlate with clinical improvement. This case suggests that IVIG therapy can be quite effective and safe for children with resistant AD.     

Generalized pustular psoriasis responsive to PUVA and oral cyclosporin therapy

A patient with acute generalized pustular psoriasis was successfully treated with a combination of oral cyclosporin (6 mg/kg per day) and photochemotherapy (PUVA). Although early inpatient treatment with weak topical steroids and PUVA produced initial improvement, the patient's clinical condition fluctuated, with the subsequent development of erythroderma. The addition of oral cyclosporin produced dramatic improvement within 1 week of its commencement. The patient remained in remission 12 months following cessation of therapy.     

Domperidone-induced systemic lupus-like syndrome

In a 64-year-old woman, fever, malar rash, widespread macular erythema, polyarthritis, generalized myalgia, and a positive reaction for antinuclear antibody developed while she was taking donperidone (30 mg daily). Proteinuria and hypocomplementemia were not found. The histopathology of cutaneous lesions was almost consistent with that of systemic lupus erythematosus. The lupus band test on the involved skin was weakly positive, but electron microscopy revealed no microtubular structure in the vascular endothelium of the involved skin. After withdrawal of the drug, there was complete resolution of the clinical signs and symptoms. Resumption of the therapy with the drug resulted in recurrence of her symptoms. The patient's antinuclear antibody reaction was weakly positive over a three-month follow-up period. To our knowledge, this is the first reported case of a clinical systemic lupus-like syndrome induced by therapy with donperidone.     

Polo-like kinase 1 is a potential therapeutic target in human melanoma

Exploration of the human melanoma cell-cycle pathway can lead to identification of new therapeutic targets. By gene set enrichment analysis, we identified the cell-cycle pathway and its member polo-like kinase 1 (Plk-1) to be significantly overexpressed in primary melanomas and in melanoma metastases. In vitro expression of Plk-1 was peaked at the G2/M phase of the cell cycle. Plk-1 knockdown/inhibition led to induction of apoptosis, which was caspase-3/8-dependent and p53-independent, and involved BID and Bcl-2 proteins. Comparative genomic hybridization/single-nucleotide polymorphism arrays showed no genetic alteration in the Plk-1 locus. Previous suggestions and significant enrichment of the mitogen-activated protein kinase (MAPK) signaling pathway pointed to potential regulation of Plk-1 by MAPK signaling. Inhibition of this pathway resulted in decreased Plk-1 expression as a consequence of G1 cell-cycle arrest rather than direct regulation of Plk-1. Inhibition of MAPK and Plk-1 had an additive effect on reduced cell viability. This study shows that in human melanoma, Plk-1 expression is dynamically regulated during the cell cycle, knockdown of Plk-1 leads to apoptotic cell death, and that a combination of Plk-1 and MAPK inhibition has an additive effect on melanoma cell viability. We conclude that combined inhibition of Plk-1 and MAPK could be a potentially attractive strategy in melanoma therapy.     

Two for two: Dual therapy with erlotinib and acitretin for twins with severe keratoderma in Olmsted syndrome

Olmsted syndrome (OS) is a rare genetic disorder, characterized by painful palmoplantar keratoderma (PPK), periorificial and intertriginous hyperkeratoses, and alopecia. Fewer than 75 cases have been described. Variants in TRPV3 result in constitutive activation of transient receptor potential vanilloid 3, leading to increased epidermal growth factor receptor (EGFR) signaling, palmoplantar epidermal hyperproliferation, and exquisite lesional pain. We describe pre-school aged twins with OS with partial improvement from oral erlotinib, an EGFR inhibitor, but dramatic reduction of their persistent palmoplantar thickening and pain from adding acitretin.     

Isoniazid induced pellagra despite pyridoxine supplementation

Although pellagra is a recognized complication of isoniazid therapy, the diagnosis may be overlooked or delayed--sometimes with life-threatening consequences. We report a case of isoniazid-induced pellagra which occurred despite pyridoxine supplementation. Drug withdrawal and supplementation with niacin led to a rapid and sustained clinical improvement. The possible mechanisms of isoniazid induced pellagra are discussed.     

Vismodegib Therapy for Basal Cell Carcinoma in an 8‐Year‐Old Chinese Boy with Xeroderma Pigmentosum

Vismodegib is an oral inhibitor of the Hedgehog signaling pathway and has been used to treat basal cell carcinoma (BCC) in adults. This article reports clearance of a nodular BCC of the nasal tip in an 8‐year‐old boy with xeroderma pigmentosum (XP). BCC can pose therapeutic challenges when located in areas that are not amenable to traditional therapies such as Mohs micrographic surgery or topical agents. Vismodegib was used at a dose of 150 mg/day to treat the boy's BCC. After 4 months of therapy, we achieved complete clinical clearance. During 21 months of follow‐up, the patient's nose remained clinically clear of tumor. Vismodegib was successfully used to treat a child with XP and nodular BCC. Our goal in using vismodegib was tumor regression while avoiding cosmetic and functional disfigurement. Vismodegib was effective in clinically clearing the tumor, and the patient has shown no signs of recurrence. Further studies are warranted.     

Use of topical povidone‐iodine resulting in an iododerma‐like eruption

Iododerma is a rare skin eruption that is usually induced by the systemic use of iodide‐containing radiographic contrast medium or treatment with oral potassium iodide therapy. Iododerma has also rarely been reported to occur following topical application of iodine. We herein report the case of a 42‐year‐old male who developed multiple pinpoint pustules on both lower extremities. Three days after the eruption began, the patient started applying topical 10% povidone‐iodine solution to the lesions. During this treatment, the lesions enlarged into multiple 2–9‐cm pus‐filled bullae, limited to the treated areas. Lesional bacterial culture swab and Gram stain were negative. Blood cultures were also negative and the patient's white blood cell count was normal. A punch biopsy specimen revealed pseudoepitheliomatous hyperplasia and dermal‐epidermal separation with epidermal necrosis and underlying abscess formation. A superficial and deep perivascular, interstitial and perifollicular infiltrate containing numerous neutrophils, with abscess formation and eosinophils was also seen. This histology was consistent with iododerma and the patient's lesions involuted following cessation of topical iodine use, leaving only post‐inflammatory hyperpigmentation. In summary, our patient likely had a folliculitis that was then treated with topical povidone‐iodine that led to iododerma. Although it remains possible that the reaction was an unusual contact hypersensitivity response, the ulceration, pseudoepitheliomatous hyperplasia and abscess formation do support an iododerma‐like eruption.     

Treatment of pustular psoriasis with infliximab

Pustular psoriasis is a severe form of psoriasis with a generalized pustular eruption. Since TNF‐α plays an important role in pustular psoriasis, we treated two patients who had not responded to established therapy regimens with the TNF‐α antagonist infliximab. Both patients showed significant improvements of their skin eruption and their general condition within three days after treatment and without any side effects. We suggest that infliximab is a therapeutic option for severe therapy‐resistant pustular psoriasis because a single well‐tolerated dose significantly ameliorates the patient's condition.     

Recurrent erythema multiforme triggered by progesterone sensitivity

Determining the underlying etiology of recurrent erythema multiforme (EM) can be a difficult endeavor. Although infection with herpes simplex virus (HSV) has been implicated in some cases, the precise trigger of a given patient's recurrent EM often remains elusive. We discuss the case of a woman with a recurrent blistering eruption that was clinically and histopathologically consistent with EM. An investigation into the etiology of the patient's EM suggested that HSV was not the causative factor but instead pointed toward a hormonal influence that we interpret as autoimmune progesterone dermatitis (APD). This case is presented to highlight the importance of considering hormonal triggers in women with recurrent EM that consistently flares during the luteal phase of the menstrual cycle, the point at which serum progesterone levels peak. A brief review of the literature regarding the diagnosis, histopathology, etiology and treatment of APD is further provided. Nasabzadeh TJ, Stefanato CM, Doole JE, Radfar A, Bhawan J, Venna S. Recurrent erythema multiforme triggered by progesterone sensitivity.