Rapid and successful effects of combining dupilumab with ultraviolet B radiation therapy in the treatment of Papuloerythroderma of Ofuji.

Papuloerythroderma of Ofuji (PEO) is an uncommon disease characterised by widespread erythroderma composed of intensely pruritic solid papules coalescing into plaques sparing the skin folds (deck-chair sign). The pathogenesis of PEO remains unclear, although T helper (Th) 2 and Th22 cells may play an important role. Dupilumab is an interleukin (IL)-4 receptor α-antagonist that effectively reduces Th2 responses, which has drawn increasing attention in the treatment of PEO patients. Here, we reported a successful case of dupilumab treatment in combination with ultraviolet B (UVB) radiation therapy, which is well known and effective for chronic itch. The patient had a significant decrease in visual analogue scale (VAS) score and eosinophil after only 1 week of treatment, which may be due to the combination effect.

Dowling-Degos Disease Presenting With Associated Epidermal Inclusion Cysts: A Case Report and Review of the Literature.

ABSTRACT: Dowling-Degos Disease (DDD) is a rare and disfiguring autosomal dominant genodermatosis characterized by reticulate hyperpigmented macules or follicular comedone-like papules in the intertriginous areas that typically presents in the third or fourth decade of life. It is a progressive disease that is often treatment-resistant. Although its association with hidradenitis suppurativa has been well described, DDD has also been less commonly reported in conjunction with other dermatologic diseases with unknown etiologic associations. Herein, we present a case of DDD with associated epidermal inclusion cysts and conduct a literature review of dermatologic conditions reported in association with DDD.

Miliarial gout: Clinical case and a brief review.

Miliarial gout is a rare clinical variant of chronic tophaceous gout characterised by tiny milia-like papules containing chalky tophaceous material. In this report, we present a case of miliarial gout in a patient with known history of gouty arthritis and review the reported cases of miliarial gout in the literature to discuss its characteristics, diagnosis and treatment.

Disseminated papular variant of Dowling-Degos disease: Histopathological features in POGLUT1 mutation.

Dowling-Degos disease is a rare benign genodermatosis. It is characterized by lentiginous hyperpigmentation and reddish-brown papules and plaques. The flexor sides and intertrigines are often affected, but the clinical appearance may vary. Mutations in different genes are responsible for the clinical manifestation. While mutations in the keratin 5 (KRT5) gene favor a reticular distribution pattern, mutations in the POGLUT1 gene lead to a disseminated, papular clinical picture. Acantholytic variants of Dowling-Degos disease have historically been referred to as Galli-Galli disease, but our case study shows that the histopathological changes can vary even within a single patient. To date, no standardized therapy concept exists. The main focus is on keratolytic measures, with varying response. New therapeutic approaches using laser technology appear to be a promising treatment option.

The deregulation of NOTCH pathway, inflammatory cytokines, and keratinization genes in two Dowling-Degos disease patients with hidradenitis suppurativa.

Dowling-Degos disease (DDD) is a rare autosomal-dominant genodermatosis and it has been associated with hidradenitis suppurativa (HS). Deregulation of NOTCH pathway has been linked to the development of HS in DDD context (DDD-HS). However, molecular alterations in DDD-HS, including altered gene expression of NOTCH and downstream effectors that are involved in the follicular differentiation and inflammatory response, are poorly defined. We report two cases of patients diagnosed with DDD-HS, one of those, under Adalimumab treatment. Our results have shown downregulation of NOTCH1/NCSTN pathway, distinct molecular profiles of inflammatory cytokines (IL23A and TNF), and a novel aberrant upregulation of genes involved in the cornified envelope (CE) formation (SPRR1B, SPRR2D, SPRR3, and IVL) in paired HS lesions of two DDD patients.

Histopathologic findings characteristic of CARD14-associated papulosquamous eruption.

BACKGROUND: Pathogenic mutations in caspase recruitment domain-containing protein 14 (CARD14) lead to CARD14-associated papulosquamous eruption, which shares clinicopathologic findings with psoriasis and pityriasis rubra pilaris. We aimed to describe distinguishing histopathologic features of CARD14-associated papulosquamous eruption. METHODS: This retrospective study examined the histopathologic features of specimens from patients with confirmed CARD14-associated papulosquamous eruption and adult patients with plaque psoriasis and pityriasis rubra pilaris. RESULTS: Lesional skin biopsies from patients with CARD14-associated papulosquamous eruption consistently showed alternating checkerboard parakeratosis and orthokeratosis, acanthosis without acantholysis, and dilated vessels in the dermal papillae, with some cases also showing follicular plugging. CONCLUSION: CARD14-associated papulosquamous eruption has a range of findings, with a predominance of features typically associated with pityriasis rubra pilaris.

Lichen planus follicularis tumidus: Immunotyping of the inflammatory infiltrate with focus on plasmacytoid dendritic cells.

Lichen planus follicularis tumidus (LPFT) is a rare clinicopathological variant of lichen planus (LP), clinically presenting with red-to-violaceous plaques studded with comedo-like lesions and keratin-filled milia-like cysts. Histopathologically, LPFT is characterized by cystically dilated follicular infundibula in the dermis, surrounded by a dense lichenoid lymphoid infiltrate with an associated interface reaction. We describe the clinicopathological features of an additional case of LPFT, focusing on the number and distribution of CD123(+) TCF4(+) plasmacytoid dendritic cells (pDCs). In our case, pDCs represented approximately 5% of the total inflammatory infiltrate, predominantly exhibiting a lichenoid distribution around the infundibula with no evidence of cluster formation, thus ruling out cutaneous lupus erythematosus. Our report is the first to describe the number and distribution of pDCs in LPFT. The results of our immunohistochemical analysis corroborate the notion that LPFT should be regarded as a rare variant of LP.

Clear cell papulosis: Dermatoscopic findings and literature review.

Clear cell papulosis is a rare skin condition that predominantly develops in patients of Asian background during their early childhood. We present a new case of clear cell papulosis of a 1-year-old Thai girl presented with multiple hypopigmented macules and papules on the lower abdomen and pubic area for 3 months and also review the previous 41 cases published in the literature since 1987. Herein, for the first time, we report the dermatoscopic features of clear cell papulosis that represents as depigmented homogenous structureless lesions. This would be beneficial for distinguishing clear cell papulosis from its differential diagnoses.

Self-healing juvenile cutaneous mucinosis: Clinical and histopathologic findings of 9 patients: The relevance of long-term follow-up.

BACKGROUND: Self-healing juvenile cutaneous mucinosis (SHJCM) is a rare disorder, and its pathogenesis and long-term prognosis are unknown. OBJECTIVE: To elucidate the clinical and histopathologic characteristics, pathogenesis, and outcome in patients with SHJCM. METHODS: Retrospective study of 9 patients with SHCJM. To complement initial findings, data collection forms were sent to the referring physicians. RESULTS: All patients had an acute onset of firm nodules. Of the 9 patients, 6 presented initially with waxy papules on the dorsum of the hands; 5 suffered from periorbital edema, and 6 had a febrile prodrome. Histopathologic assessment of the papules revealed dermal mucin deposition, whereas the nodules showed proliferative fasciitis-like features or nonspecific chronic lobular panniculitis. Laboratory studies elicited evidence of active viral infection in 2 patients (human herpes virus 6 and rotavirus). Seven cases had spontaneous resolution within 6 months, and 2 patients with incomplete resolution showed subsequent transition to fibroblastic rheumatism and an autoinflammatory rheumatologic disease, respectively. LIMITATIONS: This was a retrospective study with incomplete data from referring physicians. CONCLUSIONS: Although spontaneous complete regression is expected, patients with SHJCM need long-term follow-up because of the possible development of dematorheumatolgic conditions. The pathogenetic role of microbial agents deserves further investigation.

Clear cell papulosis: report and review.

A 12-month-old boy presented with three months of asymptomatic hypopigmented flat-topped papules on the suprapubic skin and lower abdomen. Emollients and topical steroids offered no improvementand the patient was referred to the dermatology department. Shave biopsy revealed a papillated epidermis with scattered solitary mononuclearclear cells at all levels of the epidermis and an overlying basket weave orthokeratosis. The cells were epithelioid with increased amphophilic cytoplasm. Immunohistochemical staining was positive for CK7,CEA, and CAM5.2 and negative for S100, CD1a, and Mart-1. These findings were consistent with clear cell papulosis. No treatment was recommended as these lesions were asymptomatic. However, yearlyfollow up was recommended given the resemblance of these cells to those of Paget disease. Review of the literature demonstrates a total of 31 biopsy confirmed cases with AE1, CEA, and EMA positivity and S100negativity as the most consistent staining properties. A recent retrospective review of 19 cases documents long term follow-up of at least six years and up to 21 years. The results suggested a tendency toward selfresolution and an absence of malignant progression, supporting the benign nature of these lesions.

Mutations in POFUT1, encoding protein O-fucosyltransferase 1, cause generalized Dowling-Degos disease.

Dowling-Degos disease (DDD), or reticular pigmented anomaly of the flexures, is a type of rare autosomal-dominant genodermatosis characterized by reticular hyperpigmentation and hypopigmentation of the flexures, such as the neck, axilla, and areas below the breasts and groin, and shows considerable heterogeneity. Loss-of-function mutations of keratin 5 (KRT5) have been identified in DDD individuals. In this study, we collected DNA samples from a large Chinese family affected by generalized DDD and found no mutation of KRT5. We performed a genome-wide linkage analysis of this family and mapped generalized DDD to a region between rs1293713 and rs244123 on chromosome 20 [corrected]. By exome sequencing, we identified nonsense mutation c.430G>T (p.Glu144(∗)) in POFUT1, which encodes protein O-fucosyltransferase 1, in the family. Study of an additional generalized DDD individual revealed the heterozygous deletion mutation c.482delA (p.Lys161Serfs(∗)42) in POFUT1. Knockdown of POFUT1 reduces the expression of NOTCH1, NOTCH2, HES1, and KRT5 in HaCaT cells. Using zebrafish, we showed that pofut1 is expressed in the skin and other organs. Morpholino knockdown of pofut1 in zebrafish produced a phenotype characteristic of hypopigmentation at 48 hr postfertilization (hpf) and abnormal melanin distribution at 72 hpf, replicating the clinical phenotype observed in our DDD individuals. At 48 and 72 hpf, tyrosinase activities decreased by 33% and 45%, respectively, and melanin protein contents decreased by 20% and 25%, respectively. Our findings demonstrate that POFUT1 mutations cause generalized DDD. These results strongly suggest that the protein product of POFUT1 plays a significant and conserved role in melanin synthesis and transport.

Fibroelastolytic papulosis: histopathologic confirmation of disease spectrum variants in a single case.

Fibroelastolytic papulosis is a rare, acquired fibroelastolytic disorder that presents clinically as white-to-yellow papules and plaques most commonly occurring on the neck of elderly patients. The term fibroelastolytic papulosis encompasses two closely related conditions previously described as pseudoxanthoma elasticum-like papillary dermal elastolysis (PDE) and white fibrous papulosis of the neck (WFPN). Here we present a case of a 78-year-old white female with a several-year history of numerous, asymptomatic 2-3 mm yellowish, non-follicular papules distributed symmetrically over the posterior neck, axillae, arm and antecubital fossae. Histopathologic examination revealed thickened and clumped elastotic fibers admixed with thick, sclerotic appearing collagen bundles in the mid and deep reticular dermis. Rare melanophages, loss of vertically oriented elastic fibers and scattered elastotic globes were noted in the papillary dermis. Based on the shared clinicopathologic features showed in this case, strong consideration should be made for the additional inclusion of papillary dermal elastosis as existing along the disease continuum of fibroelastolytic papulosis. This occurrence of fibroelastolytic papulosis shows unique histopathologic findings of pseudoxanthoma elasticum-like PDE, papillary dermal elastosis and WFPN, further supporting the theory that these entities exist as variants along the fibroelastolytic papulosis spectrum.

Late epidermal growth factor receptor inhibitor-related papulopustular rash: a distinct clinical entity.

We report four patients developing a late form of papulopustular rash induced by epidermal growth factor receptor inhibitors. These patients presented an unusual presentation of acneiform rash, characterized by late development (several months after treatment commenced), localization to the limbs with sparing of the face, and association with severe pruritus and Staphylococcus aureus superinfection in all cases. These clinical symptoms may suggest a distinct mechanism from the early acne-like rash frequently observed with these targeted anticancer therapies. Clinicians should be aware of this delayed adverse event, and we suggest the term 'late acneiform toxicity of EGFR inhibitors (LATE) syndrome' to permit better characterization of this clinical picture.

Dowling-Degos disease co-presenting with Darier disease.

We present a case of a patient with long-standing hyperpigmented macules and erythematous papules over his chest, abdomen, back and arms, suggestive of Dowling-Degos disease (DDD). In addition, there were hyperkeratotic papules, alternating red and white nail-bed discolouration, and V-shaped nail notching consistent with Darier disease (DD). Histology showed findings consistent with DDD and DD on separate specimens. The lack of acantholysis in areas of filiform hyperpigmented rete ridges ruled out Galli-Galli disease (GGD). DDD results from mutations in the genes encoding keratin 5 (KRT5), protein O-glucosyltransferase 1 (POGLUT1) or protein O-fucosyltransferase 1 (POFUT1), while DD results from mutations in the ATP2A2 gene. Both genes are present on chromosome 12. In this case, the patient presented with features of both DDD and DD, which suggests that either a cooperating mutation or a mutation in an unrelated gene locus may underlie the findings in this patient.

Clear Cell Papulosis: Report of a Case With Unique Clinical and Histologic Findings.

Clear cell papulosis is a rare, self-limited, benign disease of early childhood, characterized by white macules and flat papules over the milk line. Histopathologically, it is characterized by scattered clear cells throughout the basal and/or suprabasal epidermal layers, which-as clear cells of Toker of the nipple do-typically express cytokeratin 7. They also exhibit other markers expected for adenoid differentiation, such as low-molecular weight cytokeratins, carcinoembryonic antigen, epithelial membrane antigen, and mucin. The age of onset, distribution of lesions, histopathology, and its benign behavior nature help to exclude clinically similar conditions, either benign or malignant. The authors report a case of clear cell papulosis in a 7-year-old Brazilian girl in whom lesions were observed on the legs and histologically formed by solid and adenoid aggregates of clear cells, in a similar fashion than clear fetal cells of Toker.

Plasmacytoid Dendritic Cells and Type I Interferon Signature in Lichen Striatus.

BACKGROUND/OBJECTIVES: In addition to several infectious and neoplastic cutaneous entities, plasmacytoid dendritic cells (pDCs) have been shown to be involved in the pathogenesis of multiple cutaneous inflammatory and autoimmune disorders, including those characterized histologically by an "interface dermatitis" pattern such as lupus or lichen planus (LP), but their role in lichen striatus (LS), which is also known to have this histologic inflammatory pattern, has never been studied. The objective of the study was to investigate the role of pDCs in LS. METHODS: Fifteen LS patients were found in our database and were immunohistochemically tested for pDC occurrence and activity using anti-blood-derived dendritic cell antigen-2 and anti-myxovirus resistance protein A (MxA) antibodies, respectively. These individuals were also compared with 15 individuals with LP. RESULTS: pDCs were present in all individuals with LS and LP, but they were less abundant in those with LS, although MxA (surrogate marker of local type I interferon production and thus an indirect assessment of pDC activity) was similarly intense and diffuse in all individuals with LS and LP. In addition to being part of the upper dermal inflammatory bandlike infiltrate as in LP, LS cases, unlike LP, also showed perieccrine pDCs. CONCLUSIONS: pDCs constitute a central component of the inflammatory infiltrate in LS, suggesting a significant role in its pathogenesis. pDC distribution (perieccrine distribution) could also help in microscopically differentiating LS from LP.