Chronic diarrhoea and ichthyosis vulgaris: a rare presentation of Hodgkin's lymphoma.

A man in his 30s presented with several months of non-bloody diarrhoea and nausea along with conjunctivitis, diffuse ichthyosis and cellulitis in the setting of progressive neck swelling. He was ultimately diagnosed with nodular sclerosing Hodgkin's lymphoma after undergoing a broad infectious, rheumatological and neoplastic workup. This represents a rare presentation of classic Hodgkin's lymphoma and demonstrates the known alteration of cellular immunity in Hodgkin's lymphoma alongside manifestations of the profound inflammatory state associated with the disease. The patient was initiated on chemotherapy and many of his symptoms resolved. Hodgkin's lymphoma may present as a multisystemic cascade of symptoms and should be high on the differential diagnosis for a patient with lymphadenopathy and associated infectious, gastrointestinal and cutaneous symptoms.

Acquired ichthyosis, asteatotic dermatitis or xerosis? An update on pathoetiology and drug-induced associations.

Acquired ichthyosis (AI) is a relatively rare cutaneous entity characterized by transient, generalized scaling and pruritus in the absence of family history of ichthyosis or atopic disease. The hyperkeratosis in AI can range from the mild, white-to-brown scaling resembling that in ichthyosis vulgaris (IV) to the more prominent dark brown scaling phenotype, similar to that found in lamellar ichthyosis. The disease can wax and wane in relation to endogenous and/or exogenous factors. Histopathology of AI is similar to that found in IV. AI is usually of cosmetic concern to patients but can, in some cases, reflect the presence of more serious conditions, including malignancies, autoimmune diseases or metabolic disorders. In some cases, AI can be an adverse effect of a medication or the cutaneous symptom of a toxic exposure. Other conditions, such as severe xerosis or eczema, can present with clinical findings similar to AI, making diagnosis a challenge. Furthermore, cases of AI are sporadic throughout the literature and have been documented across a wide variety of medical settings distinct from dermatology, which often contribute to misdiagnosis of this disease. Definitive management requires prompt identification and treatment of the inciting factors combined with conservative therapies, which can include topical emollients, keratolytics, retinoids or corticosteroids, and in rare cases, oral retinoids.

Mood symptoms, neurodevelopmental traits, and their contributory factors in X-linked ichthyosis, ichthyosis vulgaris and psoriasis.

BACKGROUND: High rates of adverse mood/neurodevelopmental traits are seen in multiple dermatological conditions, and can significantly affect patient quality of life. Understanding the sex-specific nature, magnitude, impact and basis of such traits in lesser-studied conditions like ichthyosis, is important for developing effective interventions. AIM: To quantify and compare relevant psychological traits in men with X-linked ichthyosis (XLI, n = 54) or in XLI carrier women (n = 83) and in patients with ichthyosis vulgaris (IV, men n = 23, women n = 59) or psoriasis (men n = 30, women n = 122), and to identify factors self-reported to contribute most towards depressive, anxious and irritable phenotypes. METHODS: Participants recruited via relevant charities or social media completed an online survey of established questionnaires. Data were analysed by sex and skin condition, and compared with general population data. RESULTS: Compared with the general population, there was a higher rate of lifetime prevalence of mood disorder diagnoses across all groups and of neurodevelopmental disorder diagnoses in the XLI groups. The groups exhibited similarly significant elevations in recent mood symptoms (Cohen d statistic 0.95-1.28, P < 0.001) and neurodevelopmental traits (d = 0.31-0.91, P < 0.05) compared with general population controls, and self-reported moderate effects on quality of life and stigmatization. There were strong positive associations between neurodevelopmental traits and recent mood symptoms (r > 0.47, P < 0.01), and between feelings of stigmatization and quality of life, particularly in men. Numerous factors were identified as contributing significantly to mood symptoms in a condition or sex-specific, or condition or sex-independent, manner. CONCLUSION: We found that individuals with XLI, IV or psoriasis show higher levels of mood disorder diagnoses and symptoms than matched general population controls, and that the prevalence and severity of these is similar across conditions. We also identified a number of factors potentially conferring either general or condition-specific risk of adverse mood symptoms in the three skin conditions, which could be targeted clinically and/or through education programmes. In clinical practice, recognizing mood/neurodevelopmental problems in ichthyosis and psoriasis, and addressing the predisposing factors identified by this study should benefit the mental health of affected individuals.

Palmar hyperlinearity in early childhood atopic dermatitis is associated with filaggrin mutation and sensitization to egg.

BACKGROUND/OBJECTIVES: Palmar hyperlinearity is a typical clinical feature of Filaggrin gene (FLG) null mutations. There are reports of FLG mutations and allergic sensitization; however, reports on the relationship between palmar hyperlinearity to sensitization are limited. This study aimed to examine the association between palmar hyperlinearity and sensitization in atopic dermatitis (AD) children. METHODS: This cross-sectional, case-control study included children ˂ 6 years old with moderate-severe AD whose parents consented for mutation analysis and photographic documentation. Each child underwent genotyping to detect the eight most prevalent FLG mutations in the Japanese population: R501X, 3321delA, S1695X, Q1701X, S2554X, S2889X, S3296X, and K4022X. Clinical features and parameters including egg-specific IgE were examined, and palm photographs were evaluated by 12 trained dermatologists blinded to genotyping results. RESULTS: Of the 57 patients (age range, 2 months to 5 years; median, 22 months), 16 were heterozygotes and three were compound heterozygotes. Palmar hyperlinearity, as recognized by more than two-thirds of dermatologists, was significantly associated with FLG mutation (P = 0.002, OR = 6.98, 95% CI = 2.1-23.7), and this association was observed especially in children over 2 years. Cross-shaped crease of the thenar eminence, as known in previous reports, also demonstrated significant correlation with FLG mutation. When the children were divided according to the presence or absence of palmar hyperlinearity, the egg white-specific IgE was significantly higher in the hyperlinearity group (55.9 vs 18.3 IU/mL, P < 0.05). CONCLUSIONS: Palmar hyperlinearity indicates possible inherited barrier abnormalities of the skin in early childhood. Its identification may help to predict a more accurate prognosis, such as sensitization.

Whole exome sequencing identified two point mutations of COL7A1 and FLG in a Chinese family with dystrophic epidermolysis bullous pruriginosa and ichthyosis vulgaris.

We report a 21-year-old man with recurrent bullous eruptions and severe itching on the lower legs and feet since 5 years of age. Dry, dirty brown, tile-like scales covered his lower legs with dystrophic toenails. Nodular prurigo-like lesions, scarring papules and milia remitted after the bullous eruptions. His father and another two family members had similar but mild presentations with recurrent bullae on the lower legs. Whole exome sequencing detected the heterozygous variants of COL7A1 c.6698G>A and FLG c.7249C>T in this pedigree. COL7A1 c.6698G>A was reported in bullous dermolysis of the newborn and FLG c.7249C>T was reported in ichthyosis vulgaris. Thus, the diagnosis of dystrophic epidermolysis bullosa pruriginosa associated with ichthyosis vulgaris was made.

Concurrent Chondrodysplasia Punctata Type 2 (Conradi-Hunermann-Happle Syndrome) and Ichthyosis Vulgaris in Teenaged Twin Girls.

We present concurrent X-linked chondrodysplasia punctata and ichthyosis vulgaris in adolescent fraternal twin girls, notable for initial presentation with dry skin in adolescence, characterized by dark-brown scale typical of ichthyosis vulgaris and blaschkolinear, atrophic, scaly plaques. This constellation of findings prompted further genetic investigation. Using a multigene approach to examine 39 genes associated with congenital ichthyosis, next-generation sequencing revealed a novel heterozygous missense mutation at a mutational hotspot in the EBP gene c.439C>T (p.R147C) in conjunction with a single nonsense mutation in the FLG gene (p.R501X) in both sisters. These individuals highlight the clinical variability of Conradi-Hunermann-Happle syndrome, illustrate the possibility of co-occurrence of rare and common forms of ichthyosis, and demonstrate the utility of multigene analysis.

Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis.

BACKGROUND: The stratum corneum and tight junctions (TJs) form physical barriers in the epidermis. Dendrites of activated Langerhans cells (LCs) extend beyond the TJs to capture external antigens in mice. LCs and inflammatory dendritic epidermal cells (IDECs) are observed in the skin of patients with atopic dermatitis (AD). OBJECTIVE: We sought to investigate the characteristics of LCs and IDECs and the distribution of their antigen capture receptors in relation to TJs in normal and AD skin. METHODS: We characterized the interactions of LCs and IDECs with TJs and the expression patterns of langerin and FcεRI by using whole-mount epidermal sheets from healthy subjects and patients with AD, ichthyosis vulgaris, and psoriasis vulgaris. RESULTS: As in mouse skin, activated LCs penetrate TJs in human skin. The number of LCs with TJ penetration increased approximately 5-fold in erythematous lesional skin of patients with AD but not in nonlesional skin of patients with AD or lesions of patients with ichthyosis vulgaris or psoriasis. In contrast, IDECs localized in the lower part of the epidermis, and their dendrites extended horizontally without penetration through TJs. Although langerin accumulated on the tips of dendrites of activated LCs, FcεRI was expressed diffusely on the cell surfaces on LCs and IDECs in lesional skin from patients with AD. CONCLUSIONS: These findings highlight interesting differences between LCs and IDECs in epidermis of patients with AD, where LCs, but not IDECs, extend dendrites through the TJs, likely to capture antigens from outside the TJ barrier with a polarized distribution of langerin but not FcεRI. These behavioral differences between skin dendritic cells might reflect an important pathophysiology of AD.

Topographic and biomechanical evaluation of cornea in patients with ichthyosis vulgaris.

PURPOSE: To compare the topographic and biomechanical properties of corneas in eyes of patients with ichthyosis vulgaris (IV) and eyes of healthy individuals. METHODS: Thirty healthy individuals (control group) and 30 patients with IV (study group) were enrolled in this prospective study. Topographic measurements, including keratometry values, irregularity, and surface asymmetry index in the right eye of each participant were obtained using Scheimpflug camera with a Placido disc topographer (Sirius). Corneal hysteresis (CH), corneal resistance factor (CRF), corneal-compensated intraocular pressure (IOPcc) and Goldman-related intraocular pressure (IOPg) were measured using the Reichert Ocular Response Analyzer (ORA). Central corneal thickness (CCT) was also measured with ultrasonic pachymetry and the Sirius corneal topography system. RESULTS: Topographic parameters were not significantly different between both groups (p>0.05). Although mean CH was not significantly different between the groups, the CRF was significantly lower in patients with IV (p=0.249 and p=0.005, respectively). The CCT was significantly lower in patients with IV compared to healthy controls (p<0.001). The IOPg and IOPcc were significantly lower in the patients with ichthyosis than in healthy controls (p=0.001 and p=0.004, respectively). CONCLUSIONS: The study demonstrated that while the eyes of patients with IV had corneal topographic findings and corneal hysteresis similar to those of healthy controls, some of corneal biomechanical properties such CRF and CCT and IOP values such as IOPg and IOPcc were significantly lower in patients with IV. These results should be taken into account when planning a corneal refractive surgery and glaucoma screening for patients with IV.

Usefulness of a global clinical ichthyosis vulgaris scoring system for predicting common FLG null mutations in an adult caucasian population.

BACKGROUND: Loss of function FLG alleles were first identified as causative of ichthyosis vulgaris (IV) and were subsequently found to be major predisposing factors for atopic dermatitis (AD) and atopic disorders. OBJECTIVES: To identify independent factors associated with the clinical IV phenotype in adult caucasian patients with AD and to assess the performance of a global clinical severity score of IV in predicting common FLG null mutations. PATIENTS AND METHODS: This was a prospective study conducted from January 2007 to June 2008. Adult patients attending the department of dermatology with a diagnosis of AD with or without IV were eligible to participate. For each patient, five clinical signs of IV were scored from 0 to 3 - diffuse xerosis, hyperlinearity of palms, scales on legs, scalp desquamation and keratosis pilaris - and a global IV clinical severity score was derived (0-15). Age of onset of AD, SCORAD (SCORing of Atopic Dermatitis), family and personal history for other signs of atopy, and total immunoglobulin E were recorded. Genotyping was performed for R501X and 2282del4. Univariate and multivariate analysis for factors associated with AD or AD + IV were conducted. RESULTS: In univariate analysis, family history of atopy, global clinical severity scoring and 2282del4 FLG mutation were positively correlated with the AD + IV phenotype. Using multivariate analysis, SCORAD for AD (OR 0·94, P = 0·01) and global clinical severity scoring for AD + IV (OR 2·62, P < 0·0001) were found to be independent factors. CONCLUSIONS: The 2282del4 FLG mutation was confirmed as a good marker of early-onset disease. Moreover, our global clinical severity score yielded a good negative predictive value of common caucasian null FLG mutations.

[Clinical features of the nephrotic syndrome associated with ichthyosis vulgaris and analysis of related gene mutation].

OBJECTIVE: To study clinical features of 3 children who presented with nephrotic syndrome (NS) associated with ichthyosis vulgaris (IV), and to detect relationship between NS associated with IV in patients and FLG gene or NPHS2 gene. METHOD: Clinical and kidney pathological data of the 3 patients were analyzed and progress of pathologic damage in the patient kidney was observed through repeated percutaneous renal biopsy. Using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing, the diversity of the expression of NPHS2 gene in the 3 patients were analyzed, and FLG gene in the 3 patients and parts of their family members with IV was detected. RESULT: (1) The age of the 3 patients (patient 1 was a girl and patients 2 and 3 were boys) suffering from NS was 3 years and 8 months, 2 years and 6 months, and 5 years and 3 months, respectively. The age of onset of IV was 1 year and 6 months, 10 months, and 2 years and 6 months, respectively. All the 3 patients were resistant to steroid therapy. Despite multi-immunosuppressive therapy, no clinical response was achieved. The patients were followed up for 1.5 to 4.0 years. The patients displayed continuous proteinuria, renal function was normal, but their heights were lower than other children at the same age. (2) The older brother of patient 1 died of uremia. The other patients' family members did not have kidney disease. (3) Renal histopathology showed that the patients 1 and 2 had mild mesangial proliferative glomerulonephritis (MsPGN) and the patient 3 had minimal change disease (MCD). One and a half years after the first renal biopsy, the patients 1 and 2 underwent repeated renal biopsy. Renal histopathology showed that the 2 patients' disease developed to medium MsPGN. (4) None of the 3 patients had NPHS2 gene mutation. All the three patients had R501X and 2282del4 which are the common gene mutation type of the FLG, and all the patients were heterozygote. With the detection of the FLG gene of the part of the patients of the three families, the second patient's grandfather had the R501X homozygote mutation and the others were the R501X heterozygote mutation and 2282del4 heterozygote mutation. CONCLUSION: The 3 cases of NS associated with IV had no response to steroid and multi-immunosuppressive therapy, the renal damage observed by histopathology progressed fast. The children with NS associated with IV displayed R501X heterozygote mutation and 2282del4 heterozygote mutation of FLG gene, which suggested that the absence of response to steroid and multi-immunosuppressive therapy may be related to the FLG gene.

Subcutaneous calcification as a delayed complication of radiotherapy: a case report and review of the literature.

Subcutaneous calcification following radiotherapy is a very rare late complication. Here we report a case of radiotherapy for Hodgkin's disease in a patient with ichthyosis. Our review of the literature revealed that subcutaneous calcifications occurred in previously normal skin following irradiation. In our case the calcification developed in abnormal skin after telecobalt radiotherapy for mediastinal Hodgkin's disease. Ichthyosis is a systemic cutaneous disease and may increase the risk of late radiation complications.

Linear and whorled nevoid hypermelanosis complicated with inflammatory linear verrucous epidermal nevus and ichthyosis vulgaris.

We report a 17-year-old girl who presented with linear and whorled melanosis following Blaschko lines mainly on her trunk. Ichthyosiform lesions and linear scaling erythemas were observed respectively on her lower limbs and the dorsa of her hands, left knee, ankle and foot. No abnormality was found in systemic examination and blood tests. A biopsy specimen of pigmentation of her back showed there was increased pigmentation within the basal keratinocytes, with focal incontinentia pigmenti. Notable lymphangiectasis could also be seen in the mid part of dermis, which had never previously been described. The biopsy of scaling erythemas of her hand showed dominant hyperkeratosis with focal parakeratosis, acanthosis and papillomatous hyperplasia in the epidermis. The diagnosis of linear and whorled nevoid hypermelanosis (LWNH) complicated with inflammatory linear verrucous epidermal nevus and ichthyosis vulgaris was made in accordance with clinical and pathological manifestations. LWNH ought to be differentiated from incontinentia pigmenti and hypomelanosis of Ito.