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.

Familial pseudoxanthoma elasticum associated with multiple comedones.

Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder characterized by atypical elastic fibers that causes connective tissue abnormalities of the skin, eyes, and heart, among other organs. The disorder is rare, with a classic presentation of yellow-orange cobblestone-like papules on flexural areas, lax skin, ocular degeneration, and moribund vasculature in multiple organs. There is wide variability in the presentation of the affected organs [1]. We present two sisters with classic cutaneous findings of PXE with the additional unusual findings of numerous open comedones on the neck. To our knowledge, this is the first report of numerous open comedones in familial PXE.

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.

High incidence of internal malignancy in papuloerythroderma of Ofuji: a case series from Japan.

BACKGROUND: Although it has been reported that papuloerythroderma of Ofuji (PEO) often occurs in association with internal malignancy, the true incidence of malignancy in patients with PEO is unknown. OBJECTIVE AND METHODS: To ascertain the incidence of and relationship with internal malignancy in patients with PEO, 11 patients with PEO diagnosed at our dermatology clinic between September 2005 and June 2011 were retrospectively reviewed. RESULTS: Internal malignancy was found in 6 (54.5%) of the 11 PEO patients, and 5 cases were idiopathic PEO. In the 6 cases with associated malignancy, PEO preceded the malignancies, and the diagnosis of malignancy was made just before or shortly after the diagnosis of PEO, but the malignant process and PEO did not always run a parallel course. CONCLUSIONS: Although the limitations of this study included a relatively small sample size, the present findings show a high incidence of internal malignancy in patients with PEO.

Persistent pruritic papules and plaques: a characteristic histopathologic presentation seen in a subset of patients with adult-onset and juvenile Still's disease.

BACKGROUND: 'Persistent pruritic papules and plaques' of Still's disease represents a recently described eruption seen in a subset of patients. Most cases reported in the literature to date have been associated with adult-onset Still's disease. METHODS: We present the clinical and histopathologic examinations of three female patients ranging in age from 15 to 54 years. RESULTS: Our three patients each presented with clinical findings consistent with Still's disease. The youngest patient suffered from the juvenile form of Still's disease (systemic-onset juvenile rheumatoid arthritis). Each patient had a persistent, pruritic eruption with histopathologic findings of dyskeratosis confined to the upper layers of the epidermis as well as a sparse superficial dermal infiltrate containing scattered neutrophils. CONCLUSIONS: These cases confirm the characteristic clinical and histopathologic findings of 'persistent papules and plaques of Still's disease' and show the potential for this eruption in both the adult and juvenile age groups.

Purpura-associated congenital lymphedema.

An 8-year-old girl referred to our Department for a two-month worsening of congenital primary lymphedema of the lower limb and for the appearance of several purpuric lesions on the right thigh and knee. We diagnosed a lichenoid pigmented purpura of Gougerot and Blum in a patient with Milroy disease, complicated by an insufficiency of anterior saphena. We treated the patient with topical steroids and compression stockings, until surgical intervention of phlebectomy. We report this case for the rarity of the disease, for the even more rare association with lichenoid pigmented purpura and for cutaneous immunopathological findings.

A case of colloid milium in patient with beta thalassaemia major.

Colloid milium (CM) is a rare cutaneous condition characterized by translucent papules occurring on sun-exposed regions including the face, neck and dorsal aspects of the hands and back. Clinically, there are two variants of CM: an adult-onset type and a juvenile form. The juvenile form is inherited and presents before puberty. Probably this variant is because of an inherited susceptibility to ultraviolet (UV) light and can be transmitted as both autosomal recessive and autosomal dominant character. In this paper, we report an interesting case of adult CM in a transfused patient affected by beta thalassaemia major. The association of CM with beta thalassaemia, to our knowledge, has not been reported previously, in literature. Thus, this case represents the first case of CM associated with beta thalassaemia major. In our view, the lesion could be related to excess iron, similar to pseudoxanthoma elastic-like lesions, another cutaneous disorder which is present in beta thalassaemia. As our patient is a farmer and was exposed to sun during his work, UV light damage could have have a role in promoting the development of the disease. Other cases of CM associated with beta thalassaemia should be reported to confirm these hypotheses.

Transgrediens et progrediens palmoplantar keratoderma (Greither disease) and confluent and reticulated papillomatosis of Gougerot and Carteaud in the same patient: a coincidental finding?

A 13-year-old patient with typical findings of transgrediens et progrediens palmoplantar keratoderma that developed confluent and reticulated papillomatosis of Gougerot and Carteaud is presented. Although coexistence of the two disorders might be coincidental, the possibility of common pathogenetic pathways resulting in alterations of keratinization could be of investigational interest.

Clear cell papulosis.

A 2-year-old boy presented with multiple, hypopigmented, flat-topped papules in the pubic region and on the abdomen in a distribution pattern that followed the milk lines. The lesions had first appeared at age three months and increased in number over time. Histopathologic examination showed large clear cells within the lower epidermis, which stained positively with periodic acid-Schiff. These findings were diagnostic of clear cell papulosis, a rare condition that primarily affects young children. We review the histopathologic and immunohistochemical findings that link clear cell papulosis to clear cells of Toker and extramammary Paget disease.

Galli-Galli Disease Presenting as a Lentigo-like Eruption: A Further Clinical Feature in the Wide Spectrum of Reticulate Pigment Disorders.

Dear Editor, Reticulate pigmentary disorders (RPD) is a term used to classify a spectrum of several acquired and congenital disorders. Different clinical features can be present, including a reticular pattern and a freckle-like pattern with hyper- or hypo-pigmented macules (1). Dowling-Degos disease (DDD), an autosomal dominant genodermatosis, is the main type of RPD (2). Clinically, DDD presents with pigmented, reticulate, flexural macules and comedo-like papules on the back and neck. Galli-Galli disease (GGD) is a very rare variant of DDD, from which is clinically indistinguishable (3). A 65-year-old Caucasian male patient presented to our Department with a 6-year history of diffuse maculopapular lesions involving the trunk and the extensor and flexor regions of the upper and lower extremities (Figure 1). These lesions were small, monomorphous, erythematous macules and papules, some covered by discrete scales. Numerous brown lentiginous macules were also observed. The patients did not present with comedo-like lesions, reticulate pigmentation, pitted acneiform facial scars, palmar pits, or nail changes. Furthermore, the oral mucosa showed no lesions. The patient's familial history was negative for dermatoses. Laboratory routine tests were all negative. Topical and oral steroids as well as systemic retinoids were unsuccessful. Therefore, a punch biopsy was performed. Histologic examination showed a digitate elongations of rete ridges, with small foci of acantholysis (Figure 2, a). The epidermis showed a finger-like projections extending into the papillary dermis with increased melanin pigment. The epidermis was atrophic above the digitate proliferations and above the acantholytic foci, where necrotic and dyskeratotic keratinocytes also were found (Figure 2, b). In the papillary dermis, a lymphohistiocytic infiltrate with perivascular distribution was detected (Figure 2, a). According to the clinical and histological findings, a final diagnosis of Galli-Galli disease with lentigo-like macular lesions was established. The patients started 25 mg/day acitretin with only partial improvement. GGD is now considered a variant of DDD, from which is clinically indistinguishable (2,3). Several differential diagnosis can be considered, including Darier's and Groover's disease (2-9) (Table 1). Because of the absence of digitate proliferation of the rete ridges and the presence of yellow or brown macules, Darier's disease can be distinguished from GGD. In our patient, the involvement of the lower legs and the presence of unusual brown, lentigo-like macules were accurately evaluated, because of the major diagnostic pitfall with an extensive kind of Grover's-like eruption with lentiginous freckling (6). However, the involvement of sun-shielded areas and the histological presence of a lentiginous elongation of rete ridges led us to a final diagnosis of GGD. Regarding the pathogenesis, the alteration of the keratine 5 gene (12q13.13) may be the main factor in GGD. In GGD, a reduced amount of functional keratin 5 impairs the structure of keratin intermediate filaments (10). As a result, the structure of the epidermis is affected, leading to alterations in desmosomes and hemidesmosomes (2). Regarding the lentigo-like pattern of our patient, the additional diffusion of lentigos over shield-sites and the absence of extreme sun exposure in the patient's history ruled out the ultraviolet radiation as the main etiopathogenetic factor. In this regard, as reported by Girard et al., lentigos could represent a post-inflammatory pigmentation of the papular acantholytic lesions (10). However, as emphasized by Coper et al. (6), the persistence of lentigos for several years would contrast with this hypothesis. It is indeed known that a failure of keratin 5 may disrupt the movement of pigment-carrying melanosomes into keratinocytes. The disruption of melanosome transport is thought to be the cause of the pigmentation abnormalities seen in DDD as well as in GGD. These aspects could explain the elongated rete ridges and the altered pigmentation clinically and pathologically observed in GGD and DDD.

Pruritic papular eruption in HIV.

Pruritic papular eruption (PPE) is characterized chronic pruritus and symmetric papular eruptions on the trunk and extremities with the absence of other definable causes of itching in an HIV-infected patient. PPE seems to be much more prevalent in less developed regions of the world. The etiology of this distressing condition is unclear, although an inappropriate response to an exogenous agent, such as arthropod bites, may underlie the pathogenesis. Identifying PPE's association with the immune dysregulation of HIV and distinguishing this condition from other pruritic disorders found in HIV-infected patients is important for optimal management.