From Chilblains (Pernio) to Coeliac Disease-Should We Still Consider It Random?

Coeliac disease (CD) is a gluten-triggered, immune-mediated inflammatory disease occurring in genetically predisposed individuals, causing a variety of gastrointestinal and extraintestinal symptoms. The most common cutaneous association of CD is dermatitis herpetiformis, although recent reports have sought to link CD with other dermatological and autoimmune diseases. Chilblain, also called pernio, is usually a benign, superficial and localized inflammatory skin disorder that results from a maladaptive vascular response to non-freezing cold. We present a patient with pernio (chilblains) and newly diagnosed CD, with a significant intestinal lesion-total villous atrophy, as there are only two known cases of this feature associated with CD published in the literature. In the workup of chilblains (pernio) in children, an active case finding for coeliac disease should be conducted with coeliac-specific serology testing.

Digital Clubbing in Hereditary Hemorrhagic Telangiectasia/Juvenile Polyposis Syndrome.

Hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu Syndrome) is a rare autosomal dominant vascular disorder characterized by the presence of multiple arteriovenous malformations (AVMs) and recurrent bleeding episodes. The diagnosis is based on the Curacao criteria: (i) spontaneous recurrent epistaxis, (ii) mucocutaneous telangiectasia, (iii) AVMs of visceral organs, and (iv) first degree relatives with a similar condition (1). Due to a common genetic pathway and SMAD4 gene mutation, juvenile polyposis syndrome (JPS) may coexist with HHT (2). The disease burden is high in overlapping HHT/JPS, but digital clubbing may be the only physical finding. Continuous meticulous management may improve the quality of life and reduce the risk of complications. In 2000, a 15-year-old female patient was diagnosed with HHT based on epistaxis, multiple pulmonary AVMs, and a father who had similar symptoms. Other visceral AVMs were excluded. No telangiectasia was noted. On several occasions, pulmonary AVMs were managed with coil embolization (Figure 1), which successfully led to the resolution of dyspnea and cyanosis. Recurrent gastrointestinal bleedings led to severe transfusion-dependent anemia. Multiple polyps in the stomach, small intestine, and colon were repeatedly endoscopically removed, confirming the coexisting JPS. Genetic testing was not performed. Proctocolectomy was performed to prevent malignant transformation in the digestive tract. Telangiectasias are the dermatological hallmark of the HHT and occur in up to 90% of patients with the typical onset in childhood, becoming more apparent with increasing age. They are most frequently found on the face, with highest incidence on the nose, lips, tongue, and ears, followed by the fingertips, trunk, and feet; telangiectasia is recognized as the most common of the three criteria required for the diagnosis of HHT (1). Interestingly, no cutaneous telangiectasia developed in our patient during years of follow-up. However, pulmonary AVMs led to digital clubbing of her both fingers and toes (Figure 2). Digital clubbing is the focal enlargement of the connective tissue in the terminal phalanges, consequently changing the shape of nails, which become abnormally curved and shiny. It is associated with various infectious, neoplastic, inflammatory, and vascular conditions (3). Despite its well-known prevalence in certain conditions, the pathogenesis of this phenomenon remains elusive. Vascular, neural, and hormonal mechanisms have been considered, implicating the role of a wide range of substances, such as prostaglandins, bradykinin, estrogen, platelet-derived growth factor, hepatocyte growth factor, and growth hormone, however, none of these mechanisms provide a unifying explanation (4,5). In digital clubbing, the increased vascularity in the nail-bed leads to hyperplasia of fibrous tissue and edema, resulting in a loss of the hyponychial angle, fluctuance of the nail-bed, and an abnormal phalangeal depth ratio (5). The clinical assessment of the clubbing is based on the measurement of the distal phalangeal depth (DPD) of the finger (at the nail base) and the interphalangeal depth (IPD). A DPD/IPD ratio >1 is defined as clubbing, while a DPD/IPD ratio <1 is defined as normal (3). Clubbing is a potentially reversible phenomenon provided that the underlying condition is cured (4,5). In the context of pulmonary AVMs, abnormal communication between the pulmonary artery and pulmonary vein outside the capillary bed leads to right-to-left shunt physiology that clinically presents as dyspnea, cyanosis, and clubbing. Embolization of AVMs as the first-line therapy resolved systemic symptoms in our patient, and therefore no other treatment options were pulmonary considered further. However, 20 years later, despite the treatment, the severe clubbing of her both fingers and toes remained (Figure 2). Based on our findings, HHT should be considered in differential diagnosis of patients with digital clubbing resulting from AVMs, in particular when no skin telangiectasia is present.

Darier Disease Presenting with Recurrent Kaposi Varicelliform Eruption in a 10-year-old Boy with Seborrheic Dermatitis.

We present a case of a 10-year-old boy with a longstanding history of seborrheic dermatitis (SD) referred to the Allergy and Immunology Department for recurrent Kaposi varicelliform eruption (KVE) secondary to herpes simplex 1 (HSV-1) infection and possible primary immunodeficiency. The patient was the second child of non-consanguineous parents, with an older, healthy brother. Family history was negative for primary immunodeficiency and skin disorders. The patient's skin problems began in infancy when he was diagnosed and treated by a dermatologist for SD. From preschool age, he was under the care of a pediatric neurologist and a defectologist for a sensory processing disorder. For the last two years, the patient had been receiving chlorpromazine therapy for aggressive behavior. The first episode of KVE was diagnosed at the age of six, following potent topical corticosteroid therapy for SD and sun exposure, another known risk factor for HSV infection. After the third KVE episode, prophylaxis with oral acyclovir was initiated. The skin changes were treated with topical steroids and oral antibiotics during disease flares, with poor clinical response. On presentation, the patient was in good general health, adipose, and of unremarkable somatic status, except for numerous symmetrical yellowish-brown keratotic papules and plaques on the forehead, cheeks, and the lateral side of the neck (Figure 1). The nail plate had multiple red and white longitudinal streaks and V-shaped notches on the distal free end of the nail plate (Figure 2). The allergy tests revealed increased total immunoglobulin E (IgE) and sensitization to ragweed. Immunological workup showed normal immunoglobulins and good specific immunity (good vaccine response and normal humoral response to HSV-1) but a decreased number of T- cells (CD3+ 1020/µL (1320-3300), CD3+CD8+ 281/µL (390-1100) with normal T-cell response after antigen stimulation. The diagnosis of Darier disease (DD) was confirmed based on medical history, clinical findings and histological finding of focal suprabasal acantholysis and dyskeratosis (Figure 3). Low-dose oral retinoid therapy was initiated with modest clinical response after 6 months of therapy. In the light of recent publication (1), we initiated intravenous immunoglobulin (IVIG) substitution (400 mg/kg every month) with excellent clinical response. After 4 months, the patient's skin improved in terms of reduced inflammation, scab healing, and reduced itching. Acyclovir prophylaxis was continued. The patient had no new episodes of KVE during follow-up. Kaposi's varicelliform eruption (KVE) or eczema herpeticum occurs in a chronic inflammatory skin disease such as atopic dermatitis (AD), SD, Hailey-Hailey disease, allergic contact dermatitis, psoriasis, and DD (2). It is considered a dermatologic emergency due to its high mortality rate if misdiagnosed or left untreated (3). DD is a rare autosomal dominant genodermatosis of variable expressivity caused by mutations in the ATP2A2 gene, which encodes a sarco/endoplasmic reticulum calcium ATPase (SERCA2) highly expressed in keratinocytes (4). The onset of the disease usually occurs between the ages of 6 and 20 years. There are several clinical variants of DD: hypertrophic, verrucous, vesicular-bullous (dyshidrotic), erosive, and predominantly intertriginous forms (4). The fact that skin lesions occurred in infancy and a negative family history for skin diseases could be the reason our patient was initially misdiagnosed with seborrheic dermatitis. Due to the variable expressivity of the disease, it is impossible to exclude the diagnosis in other family members, and genetic testing of the patient and family members is therefore planned. A co-occurrence of neuropsychiatric abnormalities such as epilepsy, mental impairment, and mood disorders have been reported in patients with Darier disease, and these disorders were also present in our patient (5), indicating a correct diagnosis. Patients with DD have a high propensity for severe viral, bacterial, and fungal skin infection, probably due to local disruption of the skin barrier function or as the result of an underlying defect in general host defence (6). The occurrence of KVE in patients with DD is rare (7) and possibly caused by a disturbances in cell-mediated immunity (8). Despite abnormal findings in cellular immunity in some patients with DD, no consistent or specific abnormalities of the immune system have yet been demonstrated (6). Our patient had a decreased number of cytotoxic T-cells with normal T-cell response after antigen stimulation (in contrast with the findings of Jegasothy et al. (6)) and normal humoral response to HSV-1 infection. Recurrent KVE in our patient could be related to immune system dysfunction as an additional risk factor, along with impaired skin barrier. The excellent clinical response to IVIG speaks in favor of the role of antibody immune response in preserving the skin barrier. Occurrence of KVE in patients with mild DD (as in the case of our patient) and in some patients immediately preceding clinical skin manifestations of disease, argues very strongly against the second supposition. The severity of DD is variable and has a chronic course with frequent exacerbations and remissions. Known exacerbating triggers are: heat, sweat, sun exposure, friction, medication, and infection (9,10). The disease is chronic, and management is focused on the improvement of the skin appearance, relief of symptoms (e.g., irritation, pruritus, and malodor), and prevention or treatment of secondary infections. Topical (emollients, corticosteroids, retinoids, 5-fluorouracil, tacrolimus, pimecrolimus), physical (excision, electrodessication, dermabrasion, ablative laser, photodynamic therapy), and systemic (oral antibiotics, antiviral drugs, antimicrobial prophylaxis, vitamin A, retinoids) therapies are among the treatment options, all of which are of limited effect (2,11,12). IVIG substitution could be beneficial in some patients with Darier disease (1). In conclusion, this case highlights the association of DD with impaired cellular immunity and indicates the importance of proper diagnosis due to adequate management and avoidance of possible fatal outcomes. However, whether a subtle abnormality of T-cells in DD predisposes the patient to KVE remains unclear. Possible underlying mechanisms should be investigated further.

Treatment Options for Pediatric Psoriasis.

Psoriasis is a multifactorial inflammatory papulosquamous disease affecting 0.5% to 2% of the pediatric population. Pediatric psoriasis, presenting similar to adult psoriasis, significantly reduces patient quality of life, often requiring an individualized treatment approach for each patient. Combination and rotational therapy are helpful in reducing toxicity and maximizing efficacy. Patients with mild and limited disease severity respond well to topical treatment with steroids or vitamin D analogues, unlike moderate and severe psoriasis where sufficient remission is rarely achieved. Therefore phototherapy, systemic immunomodulators, or biologic agents are the next line of treatment to be considered. There is limited data available on the use and long-term safety of biologics in the pediatric population. Biologic agents must be administered by experienced dermatologists, only in patients with moderate-to-severe plaque psoriasis who are intolerant or refractory to other systemic conventional disease-modifying treatment or phototherapy, or if those treatments are contraindicated.

Non-suicidal self-injury among psychiatric outpatient adolescent offspring of Croatian posttraumatic stress disorder male war veterans: Prevalence and psychosocial correlates.

BACKGROUND: The children of male veterans with combat-related posttraumatic stress disorder (PTSD) are at particularly high risk of emotional and behavioral problems. However, no studies have examined non-suicidal self-injury (NSSI) in this population of youth. AIMS: To determine the prevalence and psychosocial correlates of lifetime NSSI in a sample of psychiatric outpatient adolescent offspring of Croatian PTSD male veterans. METHOD: Consecutive outpatient adolescent offspring of Croatian male PTSD veterans, aged 12 to 18 years, were assessed on the Deliberate Self Harm Inventory, the Youth Self-Report, the Family Assessment Device, the Parental Bonding Instrument and the Demographics Questionnaire. RESULTS: Of the whole sample, 52.7% of adolescents reported NSSI at least once during their lifetime. Lifetime NSSI was significantly associated with internalizing symptoms (adjusted odds ratio (OR) = 2.14; 95% confidence interval (CI): 1.04-4.42, p = .040), poor family functioning (adjusted OR = 6.54; 95% CI: 2.02-21.22, p = .002), lower maternal and paternal care (adjusted OR = 0.47; 95% CI: 0.40-0.56, p = .000 and adjusted OR = 0.82; 95% CI: 0.73-0.91, p = .000, respectively) and higher paternal control (adjusted OR = 1.84; 95% CI: 1.59-2.14, p = .000) in multivariate analysis. No association was found between lifetime NSSI and any of the socio-demographic variables. CONCLUSION: NSSI is a significant clinical problem in outpatient adolescent offspring of PTSD male veterans, which may be influenced by clinical and family factors. Interventions aimed at reducing internalizing symptoms and improving family functioning and parental behaviors are needed in the treatment of adolescent offspring of male PTSD veterans engaging in NSSI.

Photosensitivity skin disorders in childhood.

Photosensitivity in childhood is caused by a diverse group of diseases. A specific sensitivity of a child's skin to ultraviolet light is often the first manifestation or a clinical symptom of photodermatosis. It might indicate a serious underlying systemic disease such as lupus erythematosus or dermatomyositis, or a rare group of genetic skin disorders like Xeroderma pigmentosum, Cockayne syndrome, Trichothyodystrophy, Bloom syndrome, Rothmund-Thomson and Kindler syndrome as well as metabolic disorders and cutaneous porphyria. Photosensitivity secondary to topical or systemic agents may also cause photosensitivity in children. Early recognition and prompt diagnosis may prevent complications associated with unprotected exposure to sunlight and avoid actinic injuries that can lead to malignant skin changes.

Vitamin D--the true and the false about vitamin D.

Vitamin D has a positive impact on our overall health. Also there are a few conditions with strong evidence for a protective effect of vitamin D, such as bone diseases, internal cancers, multiple sclerosis, hypertension and DM type 1. Skin is the major source of vitamin D through the action of UVB light on keratinocytes, although the biologically active form of vitamin D is not exclusively produced in the kidney but also in prostate, colon, skin and osteoblast where it acts as an autocrine or paracrine hormone. In the past decade raising incidence of skin cancers, especially melanoma and its connection with sun exposure lead to a sun protection policies and practices as part of the public health campaigns. The question is how much solar UV exposure is adequate to maintain the balance between the risk and the benefit. We as dermatologists have to raise public awareness of the potential health effects from excessive exposure to UV radiation but also we have to be aware that adequate blood level of vitamin D is necessary for optimal health. So future recommendation on sun protection have to balance between the risk and benefits of sun exposure, as well as to promote vitamin D supplementation as a safe alternatives in high risk population.

Phototoxic and photoallergic skin reactions.

Indirect action of sun together with different exogenous agents (systemic medications and topically applied compounds) sometimes may result in phototoxicic and photoallergic reactions. Drug-induced photosensitivity reactions refer to the development of cutaneous disease as a result of the combined effects of a drug and light (mostly spectrum within the UVA and visible light range or UVB range). The aim of the review was to show the prominent features of phototoxic and photoallergic reactions, which occur in sun-exposed areas, including face, neck, hands and forearms. Phototoxic reactions are significantly more common than photoallergic reactions and mostly resemble to exaggerated sunburn. Photoallergic reactions appear only in a minority of individuals and resemble allergic contact dermatitis on sun-exposed areas, although sometimes may extend into covered areas. Generally, the physical examination and a positive patient's history of photosensitivity reactions on substances are of great importance for the diagnostics. The treatment of these reactions includes identification and avoidance of offending agent and application of anti-inflammatory dressings, ointments and corticosteroids.

Cicatricial alopecia as a manifestation of different dermatoses.

There are numerous dermatoses which may cause cicatricial alopecia when localized on the scalp, such as chronic discoid lupus erythematosus (DLE), lichen planus, graft-versus-host disease, dermatomyositis, scleroderma, cicatricial pemphigoid, porphyria cutanea tarda, follicular mucinosis, perifolliculitis capitis abscedens, lichen sclerosus et atrophicus, necrobiosis lipoidica, sarcoidosis, etc. Histologically, cicatricial alopecia is characterized by dermal scarring, along with absent or reduced hair follicles and reduced number of erector pili muscles. According to working classification of cicatricial alopecia by the North American Hair Society, primary cicatricial alopecia may be divided into the following categories: lymphocytic group (e.g., DLE, lichen planopilaris, classic pseudopelade (Brocq), central centrifugal cicatricial alopecia); neutrophilic group (e.g., folliculitis decalvans, dissecting cellulitis); and mixed group (e.g., folliculitis keloidalis). Over a 5-year period, 36 patients with cicatricial alopecia were hospitalized at our Department: DLE (n = 27), pseudopelade Brocq (n = 3), mucinosis follicularis (n = 2), and lichen planopilaris, folliculitis decalvans, folliculitis abscedens and folliculitis keloidalis (one patient each). Clinical evaluation was compared with histopathologic analysis of follicular architecture, as well as with the type, localization and extent of inflammatory infiltrate. Scalp biopsy was considered mandatory in all cases. Our experience indicates the need of more complex research to extend the knowledge about the etiopathogenesis and treatment options for cicatricial alopecia. We hope that this type of alopecia may attract more attention and research in the future.

Lethal injuries among the members of the 4th Guardian Brigade of Croatian Army during the 1991-1995 war.

OBJECTIVE: We analyzed the causes of deaths among the members of the 4th Guardian Brigade (GB) of the Croatian Army during the war in Croatia from 1991 to 1995: the site of the lethal injuries, the type of wounds, and estimated the severity of injuries with lethal outcome according to the Abbreviated Injury Scale. METHODS: This was a retrospective study using the files and data obtained from 4th GB, Croatian Ministry of Defense, and Croatian Ministry of War Veterans. RESULTS: During the War in Croatia from 1991 to 1995, 182 members of 4th GB were killed. One hundred fifteen (63.2%) suffered lethal injuries caused by shell fragments, 47 (25.8%) soldiers had gunshot wounds, and 20 ( 11.0%) died in traffic accidents. Mean Abbreviated Injury Scale for killed soldiers was 7.61 +/- 1.27. CONCLUSION: During the war in Croatia, the leading causes of death were mines and explosions, and, in a minor proportion, gunshot wounds.