Clinical factors predictive for histological aggressiveness of basal cell carcinoma: A prospective study of 2274 cases.

INTRODUCTION: Since surgery is the first-line treatment for basal cell carcinomas (BCC), the histological aggressiveness of the disease must be clinically predicted in order to apply optimal safety margins that ensure a high rate of complete resection while minimising the risk of recurrence. OBJECTIVES: To evaluate clinical predictive factors of histological aggressiveness of BCC, we conducted a national prospective multi-centre study. METHODS: All consecutive patients presenting for BCC surgery were included, and standardised clinical data collected, and slides were submitted for review. Trabecular, micronodular and morpheaform BCCs were classified as aggressive. RESULTS: Of the 2710 cases included, 2274 were histologically confirmed. Clinical subtyping was correct in 49.9% of superficial BCCs, 86.2% of nodular BCCs and only 22% of aggressive BCCs. By multivariate analysis, aggressive BCCs were more frequently ulcerated (45%), indurated (70%), showed adherence (8.6%), and were associated with high-risk anatomical zones (50.3%, P<0.0001). These predictive clinical features may be helpful for decision making.

[Generalized granuloma annulare: A clinicopathological study]. / Granulome annulaire généralisé : étude anatomoclinique.

BACKGROUND: Granuloma annulare (GA) is a benign granulomatous skin disorder that is generalized (GGA) in 15 % of cases. Although many case reports describe a relationship between GGA and systemic diseases, few large series have been published, and their association is debated. We present herein a series of GGA in order to describe their clinical and histological features. PATIENTS AND METHODS: We included all biopsy-proven cases of GA presenting at the dermatopathology laboratory of Strasbourg where generalized (i.e. over 10 lesions). Clinical features were obtained from patients' medical files. RESULTS: We included 35 GGA, with a sex ratio of 0.5. The mean age was 54 years. Lesions were annular or non-annular in equal measure and were symptomatic in 25 % of cases. Most patients (77 %) had an associated disease, already known in 60 % of cases, including dyslipidemia (27 %), diabetes mellitus (20 %), immunosuppressive drugs (17 %), atopy (17 %), auto-immune disease (17 %), hematological disease (14 %), and cancer (9 %). Histological analysis revealed the predominant pattern to be interstitial (54 %) rather than palisading (20 %), having no correlation with clinical type. Eosinophils were frequent (46 %) in GA but were not correlated with systemic disease or drug taking. Among the 40 % of patients treated, 50 % had a successful outcome on topical corticosteroids, doxycycline, antimalarial drugs or phototherapy. DISCUSSION: GGA differs from localized GA, which is mostly associated with an already known systemic disease, whether metabolic, infectious or neoplastic, uncorrelated with clinical or histological features, and screening is necessary.

[Acute localized exanthematous pustulosis following heparin calcium injections]. / Pustulose exanthématique aiguë localisée après injections d'héparine calcique.

BACKGROUND: Acute localized exanthematous pustulosis (ALEP) is a rare variant of acute generalized exanthematous pustulosis and is also defined by diagnostic criteria established by the EuroSCAR study group. Some twenty cases of ALEP have been described in the literature. PATIENTS AND METHODS: A 61-year-old woman suddenly developed erythematous and edematous lesions after subcutaneous heparin calcium injections in the thighs, with bullous detachment at the center of the lesions and multiple vesicles and non-follicular pustules on the edges. These lesions were centered around the injection points. There were no other skin lesions and no lesions on the oral mucosa, and the patient was apyrexial. The skin biopsy revealed an intracorneal pustule with spongiosis, as well as a prominent infiltrate of lymphocytes, neutrophils and eosinophils in the dermis, with no necrotic keratinocytes. We confirmed a definite diagnosis of ALEP, with a score of 10/12 according to the EuroSCAR criteria. A favorable outcome was quickly obtained after discontinuation of heparin injections, with only post-inflammatory pigmented macules. DISCUSSION: This case shows that heparin calcium can lead to ALEP, thus contraindicating further administration of this substance. Other causative factors consist chiefly of systemic antibiotics, spider bites and exposure to certain plants. This case is remarkable in terms of the limitation of lesions to heparin calcium injection sites.

Neutrophilic urticarial dermatosis: an entity bridging monogenic and polygenic autoinflammatory disorders, and beyond.

Neutrophilic urticarial dermatosis (NUD) has been described in 2009. Clinically, it is an eruption of rose or red macules or slightly elevated plaques, vanishing within 24 h. It occurs mostly on the trunk and the limbs. Extracutaneous signs such as fever or joint pain can be associated. The histopathological findings are a dense perivascular and interstitial infiltrate of neutrophils with leucocytoclasia but without vasculitis. It is often associated with other systemic diseases such as Schnitzler syndrome, adult-onset Still disease (AOSD), cryopyrin-associated periodic syndrome (CAPS) and Lupus erythematosus (LE). The pathogenesis of NUD is not well established but its association with CAPS and AOSD suggests that NUD is linked to autoinflammation. The management of NUD depends on the clinical findings and the potential associated systemic condition. Neutrophil migration inhibitors, such as dapsone or colchicine, and IL-1 antagonists, in particular, anakinra, are the main therapeutic options for the treatment of NUD. The prognostic value of NUD, especially when occurring in the setting of LE is not known and needs to be further investigated.

Mechanics hands in patients with antisynthetase syndrome: 25 cases.

BACKGROUND: Antisynthetase antibodies (ASA) are directed against aminoacyl-tRNA-synthetases, ubiquitous enzymes of which eight types have hitherto been described. They are seen primarily in antisynthetase syndrome (ASS), in which diffuse interstitial lung disease is associated with inflammatory myopathy, joint involvement and cutaneous signs, in particular mechanic's hands. The aim of this study was to determine the prevalence and semiological characteristics of cutaneous involvement in patients presenting ASA. PATIENTS AND METHODS: We carried out a retrospective study of the medical files of patients with ASA diagnosed at the Strasbourg University Hospital between 1994 and 2009. RESULTS: We identified 22 women and 3 men presenting ASS (n=21), dermatomyositis (n=3) or sclerodermatomyositis (n=1). Mean age at the time of diagnosis was 56 years (12-79). The most commonly seen antibodies were anti-Jo1 (n=19), with the other cases of ASA involving anti-PL12 (n=3), anti-PL7 (n=2) and anti-EJ (n=1) antibodies. Five patients died from pulmonary complications. Mechanic's hands (characteristic plaques and papules along the edge of the first fingers on both hands) were found in 10 patients with ASS (7 cases) or dermatomyositis (3 cases), at the time of diagnosis in 7 cases and during a systemic episode in 3 cases. Muscular involvement was seen in all patients: 9 had diffuse interstitial lung disease and 8 had joint involvement. Cutaneous signs regressed totally or partially in all patients under treatment; in 6 patients, worsening was seen during systemic episodes of the disease. One of the 10 patients died through pulmonary complications. DISCUSSION: Mechanic's hands are a key indicator in cases of ASA and its outcome is intimately linked with underlying systemic involvement, particularly pulmonary. The characteristic semiology enables this disorder to be recognised and allows differentiation from psoriasis or irritant contact dermatitis of the hands, and it does not vary according to antibody. Whether or not the disease is life-threatening is unaffected by the presence of this sign.

[Multifocal chalazodermic amyloidosis: The concept of immunoglobulinemic elastopathy]. / Chalazodermie amyloïde multifocale. Le concept d'élastopathie immunoglobulinémique.

INTRODUCTION: Impairment of dermal elastic tissue occurs in different entities associated with immunoglobulins or immunoglobulin-derived protein-secreting clonal plasma cell proliferations, such as amyloid elastosis, anetodermic nodular amyloidosis or monoclonal gammopathy-associated cutis laxa. We report a case of cutaneous immunoglobulinemic amyloidosis revealed by a unique chalazodermic presentation and we review elastic tissue impairment in patients with monoclonal gammopathies. OBSERVATION: A 67-year-old woman consulted for non-infiltrated anetodermic lesions on the upper left quadrant of her abdomen present for ten years. She also had a chalazodermic plaque with abnormal skin wrinkling and laxity in her right axilla. Biopsies revealed deep dermal and subcutaneous amyloid deposits. Immunohistochemistry with lambda light chain was positive. Orcein staining and electron microscopy showed extensive elastolysis. The patient presented no signs of systemic involvement, but a very small amount of monoclonal IgGλ gammopathy was detected during follow-up. DISCUSSION: This is a unique chalazodermic presentation of immunoglobulinemic amyloidosis that does not fit into a clearly-defined nosological setting. It highlights the complex interactions between immunoglobulin-derived proteins, including light and heavy chains, and elastic tissue components, leading to different types of impairment of the latter. We therefore suggest the unifying concept of immunoglobulinemic elastopathy, underscoring the need to screen for monoclonal gammopathy in patients presenting elastic tissue impairments.

Neutrophilic urticarial dermatosis: A review.

Neutrophilic urticarial dermatosis (NUD) is a rare form of dermatosis. In clinical terms, it consists of a chronic or recurrent eruption comprising slightly elevated, pink to reddish plaques or macules. The elementary lesion lasts 24 to 48hours and resolves without leaving any residual pigmentation. Extra-cutaneous signs are common, particularly fever or arthralgia. At histopathology, the dermis contains dense neutrophilic interstitial infiltrate with leukocytoclasis, but without fibrinoid necrosis of vessel walls. NUD often occurs in a setting of underlying systemic disease. The most commonly associated diseases are adult-onset Still's disease, Schnitzler syndrome, lupus erythematosus and cryopyrin-associated periodic syndromes. Treatment of NUD depends on the clinical context. Dapsone and colchicine are often effective.

Schnitzler Syndrome: a Review.

PURPOSE OF REVIEW: We focus on recent advances in diagnosis and therapeutic strategies, as well as on pathogenesis of Schnitzler syndrome. RECENT FINDINGS: New diagnostic criteria were established, and their external validity was assessed in a retrospective cohort study. The cytokine interleukin-1 (IL-1) plays a crucial role in the pathogenesis of the Schnitzler syndrome, and this explains the spectacular efficiency of IL-1 blocking therapies. The Schnitzler syndrome is now considered as a late-onset acquired autoinflammatory syndrome in which the cytokine IL-1 plays a crucial role. IL-1 blocking therapies are efficient on the inflammation-linked symptoms but not on the monoclonal component. Therefore, they probably don't reduce the risk of the development of lymphoproliferative disorders that remains the main prognostic issue. The link between autoinflammation and the monoclonal component needs to be further elucidated.

Schnitzler syndrome: validation and applicability of diagnostic criteria in real-life patients.

BACKGROUND: Schnitzler syndrome is characterized by an urticarial rash, a monoclonal gammopathy, and clinical, histological, and biological signs of neutrophil-mediated inflammation. The aim of this study was to assess the applicability and validity of the existing diagnostic criteria in real-life patients. METHODS: This multicentric study was conducted between 2009 and 2014 in 14 hospitals in which patients with Schnitzler syndrome or controls with related disorders were followed up. We compared the sensitivities and specificities and calculated the positive and negative predictive values of the Lipsker and of the Strasbourg criteria for the patients with Schnitzler syndrome and for the controls. We included 42 patients with Schnitzler syndrome, 12 with adult-onset Still's disease, 7 with cryopyrin-associated periodic disease, 9 with Waldenström disease, and 10 with chronic spontaneous urticaria. RESULTS: All patients with Schnitzler syndrome met the Lipsker criteria. According to the Strasbourg criteria, 34 patients had definite Schnitzler syndrome, five had probable Schnitzler syndrome, and three did not meet the criteria. One control met the Lipsker criteria and had probable Schnitzler syndrome according to the Strasbourg criteria. Sensitivity and specificity of the Lipsker criteria were 100% and 97%, respectively. For the Strasbourg criteria, sensitivity for definite and probable diagnosis was 81% and 93%, respectively, with a corresponding specificity of 100% and 97%. CONCLUSION: Diagnostic criteria currently in use to diagnose Schnitzler syndrome are reliable. More investigations must be done to attest their efficiency in patients with recent-onset manifestations.

[Clinicopathological aspects of terra firma-forme dermatosis]. / Dermatose en terre sèche : aspects anatomo-cliniques.

BACKGROUND: Terra firma-forme dermatosis was first described in 1987. It is characterized by the appearance in children or adolescents of dirt-like patches despite normal cleansing. The lesions are removed when the skin is rubbed with a 70°C alcohol swab. This largely unknown condition is of uncertain origin but could be due to a keratinisation disorder. PATIENTS AND METHODS: Herein we report the case of a 17-year-old male patient who, after seeking the opinions of a number of doctors, consulted in dermatology for multiple pigmented patches on the trunk and limbs that had appeared one year earlier. These lesions had persisted despite appropriate cleansing. He had no history of endocrine disorders and no familial history of pigmentation disorders. A skin biopsy revealed compact orthokeratotic hyperkeratosis resembling a second layer of stratum corneum on top of a normal layer. Very small granules were seen within this layer and PAS staining revealed spores. These skin lesions disappeared when rubbed with an alcohol swab, resulting in a diagnosis of terra firma-forme dermatosis. DISCUSSION: Where a diagnosis of terra firma-forme dermatosis is suspected, confirmation is easy to obtain using an alcohol swab. Nevertheless, the disease is not familiar to dermatologists. The most common differential diagnoses are acanthosis nigricans, reticulate and confluent papillomatosis, and Dowling-Degos disease. Their histopathological appearances are very different and skin biopsy can be useful for diagnosis. These entities belong to a group of disorders involving abnormal keratinisation and pigmentation. Anatomoclinical correlation is essential for optimal management. The appearance of the stratum corneum may play an important role in the diagnosis of terra firma-forme dermatosis.

[Pseudoxanthoma elasticum-like disease with deficiency of vitamin K-dependent clotting factors and cutis laxa features]. / Pseudoxanthome élastique variant avec déficit en facteurs de coagulation vitamine K-dépendants et perte d'élasticité cutanée.

BACKGROUND: Pseudoxanthoma elasticum (PXE)-like syndrome is characterized by the association of PXE and cutis laxa (CL) features with a deficiency of vitamin K-dependent clotting factors. It was first described in 1971 and was identified as a distinct genetic entity in 2007 with analysis of the GGCX (γ-glutamyl carboxylase) gene, which is involved in congenital deficiency in vitamin K-dependent clotting factors. Here we report a new case of this extremely rare syndrome. PATIENTS AND METHODS: A 23-year-old female patient was seen for the emergence of loose and redundant skin following extensive weight loss. She also presented a deficiency of vitamin K-dependent clotting factors. Physical examination revealed excessive, leathery skin folds in the axillary and neck regions. A skin biopsy revealed polymorphous and fragmented elastic fibers in the reticular dermis. These were mineralized, as was demonstrated by Von Kossa staining. The clinical features of CL associated with the histopathological features of PXE and vitamin K-dependent clotting factor deficiency led us to a diagnosis of PXE-like syndrome. A molecular study of the GGCX gene showed compound heterozygosity. DISCUSSION: The GGCX gene is usually responsible for PXE-like syndrome. GGCX encodes a γ-glutamyl carboxylase necessary for activation of gla-proteins. Gla-proteins are involved both in coagulation factors in the liver and in the prevention of ectopic mineralization of soft tissues. Uncarboxylated forms of gla-proteins in fibroblast would thus enable mineralization and fragmentation of elastic fibers.