Cutaneous histopathological findings of Aicardi-Goutières syndrome, overlap with chilblain lupus

We report a 2-year-old girl with developmental delay who, from the age of 1 year, developed perniotic lesions of the hands and feet initially diagnosed as chilblain lupus. Histological examination showed features of epidermal necrosis with intraepidermal bulla formation, interface dermatitis, lymphocytic vasculitis with fibrinoid necrosis and thrombi formation, both superficial and deep dermal lymphocytic infiltrate, lymphocytic eccrine hidradenitis and absence of marked dermal edema. Subsequent investigations suggested a clinical diagnosis of Aicardi–Goutières syndrome (AGS), a rare genetic leukoencephalopathy. Recently, both AGS and familial chilblain lupus, an autosomal dominant form of systemic lupus erythematosus (SLE), have been shown to be allelic thus suggesting a common pathogenic basis. In addition, a phenotypic overlap is apparent between SLE and AGS. To our knowledge, this is the first comprehensive dermatopathological report of the cutaneous lesions seen in AGS, and our paper highlights the importance of considering AGS in the differential diagnosis of perniosis and chilblain lupus.     

Association of class I HLA antigens with the clinical manifestations of Turkish patients with Behçet's disease

Summary Genetic factors appear to be important in the pathogenesis of Behçet's disease. Although it is known to be strongly associated with HLA‐B51, the association of HLA class I antigens with specific clinical findings of the disease has not been studied extensively and the few studies are conflicting. The aim of this study was to investigate the association of HLA class I alleles with the manifestations of Behçet's disease in Turkish patients. Eighty‐five patients with Behçet's disease were typed for HLA‐A, B, and C antigens with the serologic, standard microlymphocytotoxicity technique. Possible associations of the HLA complex with clinical findings of Behçet's disease were examined. Statistically significant findings are as follows (P < 0.05): increased HLA‐B51 and decreased HLA‐B35 frequency in patients with thrombophlebitis, increased HLA‐A29 and decreased HLA‐Bw6 frequency in patients with ocular involvement, decreased HLA‐Cw2 frequency in patients with erythema nodosum, and decreased HLA‐Cw7 frequency in patients with genital ulceration. Of particular note, the results of this study suggest that the presence of HLA‐B51 and the absence of HLA‐B35 can be regarded as laboratory risk factors of venous thrombosis in patients with Behçet's disease.     

Sign of Leser-Trélat associated with adenocarcinoma of the rectum

The acute onset and/or rapid increase in size and number of multiple seborrheic keratoses associated with internal malignancy is called sign of Leser-Trélat. Although some authors reject its existence, there are more than 80 well-documented case reports in the literature. Here, we report a 75-year-old man who presented with abrupt appearance of multiple seborrheic keratoses without any suspicious symptom of cancer. The screening for malignant neoplasms let us detect a rectal adenocarcinoma that was in a curative stage. This case-report illustrates a true sign of Leser-Trélat, and proves that these patients must be appropriately investigated for underlying malignancy.     

A new case of alpha-N-acetylgalactosaminidase deficiency with angiokeratoma corporis diffusum, with Ménière's syndrome and without mental retardation

alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described. We report a further case in a 47-year-old Japanese woman, the product of a consanguineous marriage. The remarkable findings in this patient were her normal intelligence, Ménière's syndrome, disturbance of peripheral sensory nerves, hearing loss and cardiac hypertrophy. alpha-NAGA enzyme activity in her plasma was 0.77% of the normal value. Other enzyme activities, such as alpha-galactosidase, beta-galactosidase, alpha-L-fucosidase, beta-mannosidase and aspartylglucosaminidase, were within normal limits. A large quantity of amino acid O-glycans was detected in her urine. Gene analysis revealed a novel point mutation (G-->A transition) at nucleotide 11018 (986 in the cDNA) resulting in an Arg-329-Gln substitution. Kanzaki disease has the same enzyme defect as Schindler disease, but the manifestations are quite different.     

Detection of the K?bner phenomenon of the skeleton of patients with psoriasis]

Psoriasis is a humorally controlled systemic disease. The degree of "eruptive strength" of manifestation results from hereditary factors (disposition) and environmental factors (provocation). We were able to demonstrate that the well-known K?bner phenomenon of the skin also occurs on the skeleton of patients suffering from psoriasis. We analysed 83 patients in whom bone scans were carried out. Our results indicate that provocation factors such as bacterial foci and/or trauma correlate with a significantly higher number of pathological scintigraphic findings, ranging up to "hot spots". Furthermore, not only did bone fractures remained scintigraphically positive for an unusually long time, traumas of the end phalanx could be demonstrated in 70% of psoriatic patients compared with 21% of a control group. Obviously, one factor alone or a combination of factors triggers the involvement of the skeleton as a "deep K?bner phenomenon". In psoriatic patients the response of bone metabolism to disturbance differs from that of non-psoriatic patients in that there is a long-lasting dysregulation. This explains the high correlation between skin and skeletal manifestation in psoriatics. Therefore the manifestation of psoriatic disease is due not to a single-stranded linear causal interrelation but to a multicausal "network pathogenesis". Bone scintigraphy is the diagnostic method of choice in patients with psoriatic osteoarthropathy and allows an objective evaluation of therapeutic success.     

Clinical, molecular and biochemical characterization of nine Spanish families with Conradi-Hünermann-Happle syndrome: new insights into X-linked dominant chondrodysplasia punctata with a comprehensive review of the literature

Summary Background Conradi–Hünermann–Happle syndrome (CDPX2, OMIM 302960) is an inherited X‐linked dominant variant of chondrodysplasia punctata which primarily affects the skin, bones and eyes. CDPX2 results from mutations in EBP (emopamil binding protein), and presents with increased levels of sterol precursors 8(9)‐cholestenol and 8‐dehydrocholesterol. Objectives To expand the understanding of CDPX2, clinically, biochemically and genetically. Methods We present one of the largest series reported to date, including 13 female patients belonging to nine Spanish families. Patients were studied biochemically using gas chromatography–mass spectrometry, genetically using polymerase chain reaction and in their methylation status using the HUMARA assay. Results In our cases, there was a clear relationship between abnormal sterol profile and the EBP gene mutation. We describe three novel mutations in the EBP gene. EBP mutations were inherited in three out of nine families and were sporadic in the remaining cases. Conclusions No clear genotype–phenotype correlation was found. Patients’ biochemical profiles did not reveal a relationship between sterol profiles and severity of disease. A skewed X‐chromosome inactivation may explain the clinical phenotype in CDPX2 in some familial cases.     

In vivo levels of IL-4, IL-10, TGF-β1 and IFN-γ mRNA of the peripheral blood mononuclear cells in patients with alopecia areata in comparison to those in patients with atopic dermatitis

Alopecia areata (AA) has been considered to be supported by an aberrant expression of IFN-γ as a result of antigen dependent immune response. On the other hand, AA sometimes concurs with atopic diseases, although the mechanism of the concurrence is not clear. This study was designed to elucidate the immune status of AA and the similarity between AA and atopic dermatitis (AD) by analysis of in vivo levels of mRNA of Th1, Th2, and suppressive cytokines of peripheral blood mononuclear cells (PBMC). Using semiquantitative RT-PCR, the levels of cytokine mRNA were measured in freshly isolated PBMC of 47 patients with AA, 15 patients with AD, and 12 healthy controls (HC). The levels of IL-4, IFN-γ, and TGF-β1 mRNA were lower in patients with AA than those in HC. The levels of IL-10 mRNA in AA were comparable with those in HC. Decreased levels of IFN–γ and TGF-β1 were also shown in patients with AD. These results indicated a similarity (decreased levels of IFN-γ and TGF-β1) between AD and AA based on the cytokine profile. In addition, decreased levels of IL-4 mRNA in AA might also explain the experience that the severity of atopic disease coincident with AA is mild in the most of cases. Next, we compared the levels of these cytokine mRNA among the three subgroups of AA that were categorized based on the severity of the symptoms: mild, severe and totalis. Although there was no significant difference between any combinations of the subgroups, there was a tendency to increase the levels of IFN-γ mRNA and to decrease the levels of IL-4 mRNA according to the severity of alopecia. However, the levels of IFN-γ mRNA in any subgroups were less than those of HC. These results suggest that IFN-γ is therefore involved in the pathogenesis of AA, although the information from PBMC is limited. In conclusion, AA might be induced by an aberrant expression of IFN-γ in individuals whose PBMC produce low amounts of IFN-γ and TGF-β1. Further analysis is therefore required to investigate the phenotypes of the population in PBMC with or without reference to regulatory T cells.