Valérie Failla

Herpes zoster in patients treated with biologicals.

Background: The incidence and severity of herpes zoster (HZ) appear increased in patients receiving tumor necrosis factor-α antagonists. Objective: To study the incidence and clinical features of HZ in 1,220 patients (4,206 patient-years) receiving either adalimumab, etanercept, infliximab, rituximab or ustekinumab. Results: Twenty-two HZ cases were identified [1.26% of total cohort; adalimumab: 11/1,546 patient-years, incidence rate (IR) 7.1; etanercept: 4/789 patient-years, IR 5.1; rituximab: 1/168 patient-years, IR 5.2; ustekinumab: 2/37 patient-years, IR 53.5; infliximab: 4/1,666 patient-years, IR 2.4]. The time to event varied widely (1.5– 108 months). Extensive HZ was reported in 45 and 32% of the cases, respectively. Persistent postzoster neuralgia (PHN; >6 months) was observed in 5/20 patients. Conclusions: The HZ incidence was 2.1-fold higher among patients over 60 years, compared with a reference population, although not statistically significant. Severe, multidermatomal HZ and persistent PHN were common.

Ustekinumab and Herpes Zoster

Background: TNF-α antagonists may increase the risk of herpes zoster (HZ), as well as the duration and severity. Recently, the monoclonal antibody ustekinumab, blocking the p40 subunit of IL-12 and IL-23, has been introduced for treating moderate to severe plaque psoriasis. There are no PubMed reports of HZ occurring in people receiving ustekinumab treatment. Common HZ was reported in clinical trials. Observation: Two patients with severe psoriasis treated with ustekinumab developed severe contiguous multidermatomal HZ 1 and 9 months after treatment initiation. Discussion: The occurrence of HZ after the instauration of ustekinumab suggests a causal relationship. Indeed, the inhibition of the p40 subunit of IL-12 shifts the immune response towards a Th1 profile with diminished IFN-γ and TNF-α expression, decreasing the antiviral immune response. Conclusion: Ustekinumab is probably a risk factor for developing HZ. Anti-HZ vaccination prior to ustekinumab treatment should be considered.

Photodynamic therapy for multi-resistant cutaneous Langerhans cell histiocytosis

Langerhans cell histiocytosis is a rare group of proliferative disorders. Beside cutaneous involvement, other internal organs can be affected. The treatment of cutaneous lesions is difficult and relies on topical corticosteroids, carmustine, nitrogen mustard, and photochemotherapy. Systemic steroids and vinblastine are used for recalcitrant skin lesions. However, some cases fail to respond. An 18-month old boy presented a CD1a+, S100a+ Langerhans cell histocytosis with cutaneous and severe scalp involvement. Topical corticosteroids and nitrogen mustard failed to improve the skin lesions. Systemic corticosteroids and vinblastine improved the truncal involvement but had no effect on the scalp lesions. Methylaminolevulinate (MAL) based photodynamic therapy (PDT) resulted in a significant regression of the scalp lesions. Control histology revealed an almost complete clearance of the tumor infiltrate. Clinical follow-up after six months showed no recurrence. Although spontaneous regression of cutaneous Langerhans cell histiocytosis is observed, the rapid effect of photodynamic therapy after several failures of other treatment suggests that photodynamic therapy was successful. As far as we know this is the first report of photodynamic therapy for refractory skin lesions. Larger series are needed to determine whether photodynamic therapy deserves a place in the treatment of multiresistant cutaneous Langerhans cell histiocytosis.

Pincer nails associated with pamidronate.

Bisphosphonates such as pamidronate are currently used in the management of metastatic bone disease and in the prevention of osteomalacia and osteoporosis. We report the first case of pincer nails after a single infusion of pamidronate infusion. A 52-year-old woman presented with thoracic pain that had been present for several months, caused by spontaneous fractures of the ribs. She had a history of thyroid and ovarian cancers. Results of extensive investigations (medical imaging, biopsies and blood testing) to exclude any metastatic process were negative, and showed only focal osteomalacia of the ribs. The patient was started on injections of salcatonin 100 U ⁄ day (Miacalcic ; Novartis Pharma SA ⁄ NV, Vilvorde, Belgium) along with oral calcium and vitamin D, with paracetamol and morphine to alleviate pain. After 6 months, the pain remained severe and it was decided to treat the patient with an infusion of pamidronate disodium 45 mg (Aredia ; Novartis Pharma). A few days after the infusion, the patient reported acute pain in her fingers. This was followed by haemorrhages of the distal nail bed of all fingernails, with tender erythematous swelling of the periungual soft tissues (proximal, distal and lateral nail folds). Within a week of the infusion, pincer nails, with severe transverse overcurvature, developed. Two weeks later, the same effect occurred on the toenails, but was much less pronounced. Two biopsies were taken from the distal and proximal parts of a fingernail bed. On histological examination, only aspecific onycholysis was seen. Fungal cultures had no growth. Radiography of the hands did not detect any bone alteration. The only other medications the patient was taking were atenolol, levothyroxin, alprazolam and lorazepam, which she had been taking at the same dosages for > 5 years without any side-effects. Pain from the resulting constriction of the nails interfered greatly with the patient s daily activities, and surgical treatment was planned. This had to be postponed because 4 weeks after the pamidronate infusion, the patient developed acute gingival recession that led to the extraction of four teeth. After 4 months, the subungual haemorrhages had completely disappeared, and the nail condition improved substantially; the overcurvature was still present but to a lesser degree. The pain was also greatly lessened. Hence, surgery was postponed, and the patient monitored for another 2 months, by which time (6 months after the pamidronate infusion), all fingernails had almost recovered their normal shape except for four lateral nail areas that remained ingrown and painful. These improved after chemical cauterization of the corresponding area of the lateral matrix. Pincer nails are quite common on the toes but are rare on the fingers. Development of pincer fingernails has been reported with psoriasis, subungual tumours, tinea unguium, Kawasaki disease, metastatic gastrointestinal carcinoma, systemic lupus erythematosus and use of beta-blockers. Whether given intravenously or orally, bisphosphonates are eliminated quickly from the bloodstream, with the halflife in plasma being about 35 min. The portion reaching the kidneys is eliminated unmetabolized through the urine within a few hours. The remainder, also unmetabolized, is deposited in the skeleton. The half-life in bone is very long (about 1 year) and this explains the long-lasting sideeffects. The mechanisms underlying the sudden development of pincer nails after infusion of pamidronate remain unclear. It is well established that pincer nail deformation may result from an enlargement of the distal interphalangeal joint. However, in our patient, no swelling was found by the rheumatologists at her first presentation, and no alteration in the bones of the hands was seen on radiographs. Psoriasis precipitated by beta-blockers was excluded by the biopsy. The abrupt start of acute pain associated with splinter haemorrhages may represent an involvement of the nail-bed vessels (nail-bed toxicity or inhibition of nail-bed angiogenesis is seen with some chemotherapeutic drugs such as sunitinib and sorafenib) with subsequent oedema of the bed, which would then be responsible for the transverse overcurvature of the plate. To of our knowledge, this is the first case reported of such a side-effect. There are seven criteria used to assess the relationship between drugs and their possible side-effects (imputation). They are divided into two groups, the chronological (C) score and the semiological (S) score criteria; the sum of Viewpoints in dermatology • Correspondence

Seasonal variations in vitamin D levels in melanoma patients: a single-centre prospective pilot comparative study

Background  More than 90% of vitamin D synthesis is dependent on UV exposure. Photosensitive disorders such as lupus erythematosus, protoporphyria and xeroderma require strict sun avoidance, and vitamin D deficiency has been demonstrated in these patients. Melanoma patients are also instructed to avoid sun exposure and may hence be expected to be vitamin D deficient.

PSORIASIS: STATE OF THE ART 2013

Abstract Psoriasis affects about 2 to 3% of the caucasian population. It is a chronic inflammatory disease affecting predominantly the skin with the involvement of autoimmune mediated mechanisms. Typical pathogenic features include an increased renewal of epidermal keratinocytes, the enlargement of the germinating compartment, papillomatosis, altered epidermal differentiation, angiogenesis, lymphangiogenesis and inflammatory infiltration. Several types of psoriasis are distinguished and may be present simultaneously in some patients. Up to 20 candidate genes have been evidenced in psoriasis. Genetic variability explains different types of the disease and influences response to therapeutics. Furthermore, psoriasis is triggered or aggravated by infections, traumatisms, medications, stress, tobacco, alcohol and endocrine factors. Severe psoriasis is frequently associated with co-morbidities as obesity, diabetes, metabolic syndrome and cardiovascular diseases. For this reason, the similar pathogenic mechanisms of psoriasis and other IMID‘s (Immune Mediated Inflammatory Diseases) and the use of systemic treatments shared with other specialties, an updated vision of psoriasis for the internist is mandatory.

Chronic Idiopathic Penile Edema: Three Cases and a Review of the Literature

Chronic idiopathic penile edema (CIPE) is an exceptional entity with disabling persistent lymphedema of the penis, affecting accessorily the scrotum and the pubis. The onset presents with recurrent swelling of the external genitalia, regressing spontaneously. After 2-3 years the swelling becomes progressively persistent. Mictional and erectile dysfunctions are not uncommon. A thorough work-up including RX, ultrasound examination, CT scanning, MRI imaging, serology and extensive blood testing should be performed to exclude underlying causes, including neoplastic, infectious, vascular and inflammatory diseases. CIPE is associated with significant psychological and functional impact. Surgical correction is the sole therapeutic option. Three patients with CIPE and a review of the literature are presented in order to increase awareness of this rare condition.

Congenital infantile digital fibromatosis: a case report and review of the literature

Infantile digital fibromatosis (IDF) is a rare benign fibroproliferative tumor of early childhood. IDF preferentially affects the fingers and the toes. Malignant transformation or metastases have never been reported. Surgical treatment has been advocated previously but local recurrences were observed frequently. Recent literature supports clinical surveillance without any medical or surgical intervention as spontaneous regression usually occurs after two to three years. A six-month-old Caucasian girl with IDF on the left fourth digit is presented here. The tumor progressively increased in size after birth. Topical imiquimod cream and diflucortolone valerate cream, both displaying antifibrotic properties, had no effect on tumor growth. Currently the lesion size remains stable without any treatment. Early recognition of IDF is important in order to avoid unnecessary surgical intervention that may prove to be potentially aggravating, unless serious functional or cosmetic concerns intervene. Parents should be reassured concerning the benign nature of IDF and be informed that spontaneous involution of IDF might be expected.

Childhood Herpes Zoster-Triggered Guttate Psoriasis

Psoriasis is commonly triggered or exacerbated by various stress factors, certain drugs, or streptococcal throat infections. Viral infections such as HIV, CMV, chikungunya, or herpes simplex virus are very uncommon triggers for psoriasis. Cases of varicella-triggered psoriasis are exceptional. A 7-year-old boy with a previous history of guttate psoriasis presented with generalized acute guttate psoriasis shortly after an extensive herpes zoster infection affecting the first and second left lumbar dermatomes. INF-alpha and granulocyte monocyte colony stimulating factor influence peripheral monocytes to transform into INF-dendritic cells (DCs), similar to those involved in psoriasis. These INF-DCs express toll-like receptors 7 and 8, which are responsive to viral single stranded RNA. Hence, viral infections and interferon (INF)-alpha may play a role in triggering psoriasis.