Dowling-Degos Disease Research Articles

Galli-Galli disease is an acantholytic variant of Dowling-Degos disease: Additional genetic evidence in a German family

Galli-Galli disease is an acantholytic variant of Dowling-Degos disease: Additional genetic evidence in a German family

Molekularne podłoże keratynopatii

Keratin disorders are a group of rare bullous skin diseases. They are caused by mutations in genes encoding keratins – the main structural proteins of intermediate filament cytoskeleton of epithelial cells and also one of the major components of hair and nails. Different pairs of keratins are the expressed depending on the skin layer, thus variability in the course of keratinopathies is observed. This disorders are inherited in autosomal dominant pattern mostly. Mutations occur in different regions of the keratin genes. In most of these diseases correlation between the location of mutations, and the severity of clinical symptoms can be observed. The most common keratin disorder is epidermolysis bullosa simplex (EBS), which is caused by mutations in KRT5 and KRT14. These genes are expressed in basal layer of epidermal cells. Depending on the effect of the molecular defect in the protein, EB simplex can phenotype of EBS may be highly different - from mild and localized forms, to severe and generalized. Another disease from this group is epidermolytic ichthyosis, which is caused by mutations in KRT1 and KRT10, expressed in epidermal suprabasal cell layer. This paper contains an overview of selected keratin disorders in terms of their molecular pathology. Beside those mentioned above, ichthyosis bullosa of Siemiens, pachyonychia congenita, and Dowling-Degos disease are also described.

Disorders of Pigmentation

The disorders of skin pigmentation discussed in this chapter fall into two categories: disorders of hyperpigmentation (melasma, postinflammatory hyperpigmentation, drug-induced hyperpigmentation, erythema dyschromicum perstans, lentigines, confluent and reticulated papillomatosis of Gougerot and Carteaud, and Dowling-Degos disease) and disorders of hypopigmentation (vitiligo, albinism, piebaldism, and idiopathic guttate hypomelanosis). The definition, epidemiology, etiology and pathogenesis, diagnosis, differential diagnosis, and treatment are discussed for each condition. Figures show examples of melasma, hyperpigmentation secondary to acne, vitiligo and its response to treatment with tacrolimus and with narrow-band ultraviolet B (UVB) light, Vogt-Koyanagi-Harada syndrome, and piebaldism. A table lists therapeutic approaches to vitiligo. This chapter contains 182 references.

Disorders of Pigmentation

The disorders of skin pigmentation discussed in this chapter fall into two categories: disorders of hyperpigmentation (melasma, postinflammatory hyperpigmentation, drug-induced hyperpigmentation, erythema dyschromicum perstans, lentigines, confluent and reticulated papillomatosis of Gougerot and Carteaud, and Dowling-Degos disease) and disorders of hypopigmentation (vitiligo, albinism, piebaldism, and idiopathic guttate hypomelanosis). The definition, epidemiology, etiology and pathogenesis, diagnosis, differential diagnosis, and treatment are discussed for each condition. Figures show examples of melasma, hyperpigmentation secondary to acne, vitiligo and its response to treatment with tacrolimus and with narrow-band ultraviolet B (UVB) light, Vogt-Koyanagi-Harada syndrome, and piebaldism. A table lists therapeutic approaches to vitiligo. This chapter contains 182 references.

Doença de Dowling-Degos: apresentação clínica e histopatológica clássica

Dowling-Degos disease (DDD) is a rare genetic disease of the skin (reticulate pigmented anomaly), clinically characterized by flexural brown pigmented reticulate macules, comedo-like papules on the back, neck and pitted perioral or facial scars. We present the case of a 51 year-old man with macrocomedo-like lesions, pitted scars, cysts, hyperpigmented macules in his back, chest, axillae, neck, groin and face. The patient reported having two children, three brothers and a father with a similar condition. The histopathology of the skin biopsies was very characteristic of Dowling-Degos disease, showing dilated follicular, fingerlike projections called rete ridges (dermal pegs), with thinning of the suprapapillary plates, resulting in an "antler-like" pattern and increased pigmentation of the basal layer.

Dowling-Degos Disease involving the vulva and back: Case report and review of the literature

Dowling-Degos disease is a rarely encountered pigmentary disorder in which small brown-to-black macules appear in a clustered or reticulated pattern primarily at flexural sites. It usually occurs as an autosomal dominant trait but sporadic cases have also been reported. Dowling-Degos disease is sometimes associated with other cutaneous abnormalities, many of which appear to occur as a result of abnormal follicular development. The histology is distinctive with marked, heavily pigmented, slender, and often branched, elongation of the rete ridges. Dowling-Degos disease is caused by one of several loss-of-function mutations in the keratin 5 gene. Similar mutations are found in patients with Galli-Galli disease and that disorder is now considered to be a subset of Dowling-Degos disease. Medical therapy is ineffective but two patients have responded well to ablative laser therapy. We report a patient with the sporadic form of the disease who developed pigmented macules in the rarely involved sites of the lower back and vulva. Her vulvar lesions were treated with Er:YAG laser ablation.

Atypical Variant of Galli–Galli Disease (Grover-Like Eruption With Lentiginous Freckling) in a Liver Transplant Patient

Galli-Galli disease is considered as a rare variant of Dowling-Degos disease, sharing the same clinical features of reticulate hyperpigmentation of the flexures. Histopathologically, there is acantholysis and suparabasal lacunae. Grover disease (transient acantholytic dermatosis) is a transient dermatosis which clinically presents as an eruption of erythematous excoriated papules located on the trunk and histologically with dyskeratosis and acantholysis. Grover disease has occasionally been reported in patients with chronic renal failure, human immunodeficiency virus infection, hematological malignancies, bone marrow allotransplantation, and renal transplantation. We report herein a case of atypical variant of Galli-Galli disease occurring in a liver transplant patient in whom the leading sign of reticulate hyperpigmentation of the large flexures was lacking. Instead, Grover-like, erythematous, keratotic, excoriated papules and lentigo-like macules with predilection for the trunk were found. Histopathology of both, an excoriated papule and a lentigo-like macule revealed the diagnostic features of Galli-Galli disease namely, elongated, pigmented, finger-like rete ridges, intraepidermal lacunae and acantholysis. However, serial sections of the lentigo-like macule were needed to reveal some suprabasal and subcorneal lacunae with minimal acantholysis. Thus, a good clinicopathological correlation is essential to make the right diagnosis of Galli-Galli disease. Although Grover disease has been described in the setting of solid organ transplantation and immunosuppression, this is the first report of an atypical variant of Galli-Galli disease occurring in a liver transplant patient.

A novel heterozygous nonsense mutation of keratin 5 in a chinese family with Dowling–Degos disease

Dowling-Degos disease (DDD; MIM 179850) is an autosomal dominant genodermatosis caused by mutations in keratin 5 gene (KRT5). KRT5 is specifically expressed in basal layer of epidermis and plays an important role in protecting epithelial cells from mechanical and non-mechanical stresses. We analysed the molecular basis of DDD in a Chinese family. Genomic DNA of the Chinese DDD family and a matched control cohort was isolated according to standard techniques. All exons of the KRT5 gene and adjacent exon-intron border sequences were amplified using PCR and directly sequenced. We identified a novel keratin 5 (K5) nonsense mutation designated c.C10T (p.Gln4X) in exon 1 of the KRT5 gene. Our data expand the spectrum of mutations in the KRT5 gene underlying DDD.

Dowling–Degos disease presenting as hypopigmented macules

Dowling–Degos disease presenting as hypopigmented macules

A Large Mutational Study in Pachyonychia Congenita

Pachyonychia congenita (PC) is a rare autosomal dominant skin disorder characterized predominantly by nail dystrophy and painful palmoplantar keratoderma. Additional clinical features include oral leukokeratosis, follicular keratosis, and cysts (steatocysts and pilosebaceous cysts). PC is due to heterozygous mutations in one of four keratin genes, namely, KRT6A, KRT6B, KRT16, or KRT17. Here, we report genetic analysis of 90 new families with PC in which we identified mutations in KRT6A, KRT6B, KRT16, or KRT17, thereby confirming their clinical diagnosis. A total of 21 previously unreported and 22 known mutations were found. Approximately half of the kindreds had mutations in KRT6A (52%), 28% had mutations in KRT16, 17% in KRT17, and 3% of families had mutations in KRT6B. Most of the mutations were heterozygous missense or small in-frame insertion/deletion mutations occurring within one of the helix boundary motif regions of the keratin polypeptide. More unusual mutations included heterozygous splice site mutations, nonsense mutations, and a 1-bp insertion mutation, leading to a frameshift and premature termination codon. This study, together with previously reported mutations, identifies mutation hotspot codons that may be useful in the development of personalized medicine for PC.

Unique brown star shape on dermatoscopy of generalized Dowling-Degos disease

Unique brown star shape on dermatoscopy of generalized Dowling-Degos disease

A Case of Dowling-Degos Disease on the Vulva

Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis and this disease is a genetically determined disturbance of epidermal proliferation. It is characterized by acquired, slowly progressive pigmented lesions that primarily involve the great skin folds and flexural areas such as the axilla, neck, limb flexures, the inframammary area and the inguinal folds. The vulva is an unusual location for DDD. A 41-year-old woman presented with a 10-year history of multiple, small, reticulated and brownish macules distributed symmetrically on the bilateral external genital regions. We found no other similarly pigmented skin lesions on her body, including the flexural areas. There was no known family history of similar eruptions or pigmentary changes. The histologic examination showed irregular rete ridge elongation with a filiform or antler-like pattern and basilar hyperpigmentation on the tips. Fontana-Masson staining showed increased pigmentation of the rete ridges and the S100 protein staining did not reveal an increased number of melanocytes in the epidermis. From these findings, we diagnosed this lesion as DDD.

Coexistence of Vulvar Dowling-Degos Disease and Seborrhoeic Keratosis

Dowling-Degos disease is a rare autosomal dominant inherited pigmentary disorder, mostly confined to the flexures. Diagnosis is established based on the clinical and histopathological correlation. The authors describe the clinical case of a female patient with vulvar involvement and multiple seborrhoeic keratoses on her face, neck, and upper trunk. Major and minor clinical manifestations of Dowling-Degos disease are discussed, with particular emphasis on the genital location of the lesions, which is a rare finding. Also the presence of seborrhoeic keratosis is discussed as a coincidence or a true-associated phenomenon.

Galli-Galli Disease: A Rare Acantholytic Variant of Dowling-Degos Disease

Galli-Galli disease is a rare acantholytic variant of Dowling-Degos disease, with few cases reported in the literature. We describe a case of Galli-Galli disease and review the literature.

Caso para diagnóstico

Dowling-Degos disease is a rare genodermatosis characterized principally by progressive reticulate hyperpigmentation of the flexures. Although the condition is benign, it may be associated with skin malignancies. Furthermore, the characteristic skin changes may be psychologically and socially detrimental to the patient as a result of the unsightliness of the condition. The present report describes a case in which this disease was associated with a keratoacanthoma, and summarizes current concepts on this skin disorder.

Systematic mutation screening of KRT5 supports the hypothesis that Galli-Galli disease is a variant of Dowling-Degos disease

Galli-Galli disease (GGD) is a rare genodermatosis. Its clinical presentation is identical to that of Dowling-Degos disease (DDD), but the presence of the histopathological feature of acantholysis in GGD is thought to distinguish the two disorders. Mutations in the keratin 5 gene (KRT5) have been identified in the majority of patients with DDD and in a small number of patients with GGD. To provide further support for the hypothesis that GGD is merely a variant of DDD, and to examine whether acantholysis is genuinely rare in DDD or rather a common but under-reported histological feature of DDD. We conducted the first systematic mutational investigation of patients with GGD and re-examined the histopathology of patients previously assigned a diagnosis of DDD. For the mutational investigation, KRT5 was sequenced in seven unrelated patients with clinically and histopathologically confirmed GGD. In addition, the histopathological findings of six patients with DDD were re-evaluated. The mutation c.418dupA was found in five patients with GGD. The typical histopathological features of GGD were identified in six patients who had previously been assigned a diagnosis of DDD. We found further evidence to suggest that GGD is indeed a variant of DDD and not a distinct disease entity. Two facts in particular support this conclusion: the same KRT5 mutation was found in patients with GGD and in patients with DDD, and acantholysis seems to be present in a large number of patients who had previously been assigned a diagnosis of DDD.

Galli-Galli Disease Presenting as Lichenoid Papules in the Flexures

Galli-Galli disease is a rare genodermatosis currently regarded as an acantholytic variant of Dowling-Degos disease. The 2 diseases have the same clinical features: reticular hyperpigmented macules in the great skin folds, erythematous scaly papules and plaques, comedo-like lesions, and pitted perioral scars, and the only differentiating characteristic is the histological finding of acantholysis, usually without dyskeratosis. We describe the case of a patient with hyperpigmented papules in the skin folds as the only sign of Galli-Galli disease, and we present a review of the literature.

Presentación de enfermedad de Galli-Galli como pápulas liquenoides flexurales

Galli-Galli disease is a rare genodermatosis currently regarded as an acantholytic variant of Dowling-Degos disease. The 2 diseases have the same clinical features: reticular hyperpigmented macules in the great skin folds, erythematous scaly papules and plaques, comedo-like lesions, and pitted perioral scars, and the only differentiating characteristic is the histological finding of acantholysis, usually without dyskeratosis. We describe the case of a patient with hyperpigmented papules in the skin folds as the only sign of Galli-Galli disease, and we present a review of the literature.

Identification of novel and known KRT5 and KRT14 mutations in 53 patients with epidermolysis bullosa simplex: correlation between genotype and phenotype

Basal epidermolysis bullosa simplex (EBS) is a hereditary skin blistering disorder resulting in most cases from missense mutations in the keratin 5 (KRT5) or keratin 14 (KRT14) genes. To identify the underlying mutations in different EBS subtypes and correlate genotype and phenotype. Mutation analysis was performed in 53 patients with EBS and their families by direct sequencing of the KRT5 and KRT14 genes. We identified 39 different mutations, of which 15 have not been published previously. Three novel deletion/insertion mutations, among them one in-frame duplication, were associated with the rare phenotype of EBS with mottled pigmentation. We identified for the first time a patient with compound heterozygosity for KRT5 mutations causing Dowling-Degos disease and EBS. Identification of novel mutations and genotype-phenotype correlations in EBS allow improved understanding of disease pathogenesis as well as better patient management.

Three cases of Dowling Degos disease in two families

Dowling Degos disease is a rare condition inherited as autosomal dominant trait characterized by numerous, asymptomatic, symmetrical, progressive, small, round-pigmented macules over axillae and groins, face, neck, arms and trunk, scattered comedo-like lesions (dark dot follicles) and pitted acneiform scars. Histopathology is diagnostic. We are hereby reporting three cases of Dowling Degos disease belonging to two families. Our first and second case belonged to the same family, whereas our third case belonged to different family. In our series, all the patients had onset after puberty. All three cases had reticulate pigmentation over face and/or flexures, black comedones and follicular pits. On histopathological examination of the skin biopsy taken from the lesion over the back, all these patients showed classical histopathological features of Dowling Degos disease. We feel that one should investigate the patient presenting with reticulate pigmentation over the face and flexures with blackish comedone-like lesions, because histopathological features of this condition are unmistakable.