Skin erythematous migrant lesions consistent with histologically confirmed dermal arteriolar thrombosis connected to APS.

Antiphospholipid syndrome (APS) is an acquired thrombophilic disorder related to the presence of antiphospholipid antibodies (LAC, anticardiolipin, anti Beta2-glycoprotein) known to cause venous and arterial thrombosis and recurrent pregnancy loss. Skin disorder is a frequent finding usually due to vascular thrombosis involving the dermal layer and can be either localized or widespread causing necrosis and ulceration of the skin, without histological evidence of vasculitis. We present a case of a woman with APS with both arterial and venous thrombotic involvement associated with an atypical dermatological manifestation histologically consistent with a pauci-inflammatory intermediate-deep dermal arteriolar platelet-mediated thrombosis that appeared despite anticoagulation with warfarin and responding to the addition of antiplatelet therapy.

Pyoderma gangrenosum associated with pseudo-Pelger-Huet anomaly in a patient with idiopathic myelofibrosis.

Pseudo-Pelger-Huët anomaly is a condition in which almost all the granulocytes are hyposegmented and/or hypogranulated. It is typically recognized in peripheral blood smears and represents a marker of several disorders, such as myeloproliferative diseases and myelodysplasia. The occurrence of the pseudo-Pelger-Huët anomaly in the cutaneous infiltrate of pyoderma gangrenosum is very rare. We describe the case of a 70-year-old man with idiopathic myelofibrosis who developed pyoderma gangrenosum. Histological examination showed an infiltrate consisting of granulocytic elements with features of dysmaturity and segmentation anomalies (hypo- and hypersegmented forms), suggestive of pseudo-Pelger-Huët anomaly. Methylprednisolone treatment resulted in progressive improvement of pyoderma gangrenosum.

Milia-like calcinosis cutis in Down syndrome: a new case with a review of the literature.

We report an 11-year-old girl who presented with white papules on the dorsal and palmar region of the hands bilaterally. The parents reported that the lesions had appeared four months before and some had resolved spontaneously. The girl was suffering from celiac disease, Down syndrome, and alopecia areata treated with topical corticosteroids. At the first visit, the girl presented with alopecia areata, corticosteroid acne, and a dozen white papules located on the hands. On dermoscopy, a whitish structureless area was seen. Histological examination showed the presence of calcium deposits without tissue damage, thus confirming the diagnosis of milia-like idiopathic calcinosis cutis. At 6-month follow up, the lesions had completely disappeared. Milia-like idiopathic calcinosis cutis is a benign cutaneous disorder consisting of calcium deposits in an apparently undamaged dermis and is typically associated with Down syndrome. Up to a quarter of patients have coexisting syringomas. The milia-like papules tend to self-resolve as patients reach adulthood, so a wait-and-see approach is recommended.

Late granuloma formation secondary to hyaluronic acid injection.

Hyaluronic acid injection to rejuvenate or to correct defects is a very common practice in aesthetic medicine. Although it is considered highly safe because of biocompatibility and biodegradability, adverse reactions can occur. Herein, we report a patient with foreign body granuloma formation that presented as multiple subcutaneous nodules on both arms, following injections of hyaluronic acid performed about six years earlier. Our case is unique with respect to timing and area of granuloma appearance.

Factor H interferes with the adhesion of sickle red cells to vascular endothelium: a novel disease-modulating molecule.

Sickle cell disease is an autosomal recessive genetic red cell disorder with a worldwide distribution. Growing evidence suggests a possible involvement of complement activation in the severity of clinical complications of sickle cell disease. In this study we found activation of the alternative complement pathway with microvascular deposition of C5b-9 on skin biopsies from patients with sickle cell disease. There was also deposition of C3b on sickle red cell membranes, which is promoted locally by the exposure of phosphatidylserine. In addition, we showed for the first time a peculiar "stop-and-go" motion of sickle cell red blood cells on tumor factor-α-activated vascular endothelial surfaces. Using the C3b/iC3b binding plasma protein factor Has an inhibitor of C3b cell-cell interactions, we found that factor H and its domains 19-20 prevent the adhesion of sickle red cells to the endothelium, normalizing speed transition times of red cells. We documented that factor H acts by preventing the adhesion of sickle red cells to P-selectin and/or the Mac-1 receptor (CD11b/CD18), supporting the activation of the alternative pathway of complement as an additional mechanism in the pathogenesis of acute sickle cell related vaso-occlusive crises. Our data provide a rationale for further investigation of the potential contribution of factor H and other modulators of the alternative complement pathway with potential implications for the treatment of sickle cell disease.

Are there distinct clinical and pathological features distinguishing idiopathic from drug-induced subacute cutaneous lupus erythematosus? A European retrospective multicenter study.

BACKGROUND: Clinical and pathologic criteria to distinguish drug-induced subacute lupus erythematosus (DI-SCLE) from idiopathic (I-SCLE) are controversial. OBJECTIVE: The aim of the survey was a retrospective analysis of a consistent number of iatrogenous and idiopathic SCLE cases, by means of clinical and histopathologic investigation. METHODS: Eleven European university dermatology units collected all diagnosed cases from January 2000 to December 2016. Board-certified dermatopathologists reviewed the histopathologic specimens. Statistical analysis included Student t test, exact test of goodness-of-fit, Fisher's exact test, and the Cochran-Mantel-Haenszel test for repeated measures. RESULTS: Out of 232 patients, 67 (29%) belonged to the DI-SCLE group. Patients with DI-SCLE were significantly older and reported more systemic symptoms than those with I-SCLE. No statistical differences were found for presentation pattern or serology, while histopathology showed a significant association of mucin deposition (P = .000083), direct immunofluorescence positivity for granular immunoglobulin M, and C3 deposits on the basement membrane zone (P = .0041) for I-SCLE and of leukocytoclastic vasculitis (P = .0018) for DI-SCLE. LIMITATIONS: This is a retrospective study. CONCLUSION: An integrated clinical and immunopathologic evaluation is useful to differentiate I-SCLE from DI-SCLE. Older age at onset and more frequent systemic symptoms characterize DI-SCLE. Mucin deposition and immunofluorescence findings are found in I-SCLE, and leukocytoclastic vasculitis is found in DI-SCLE.

Pediatric CD8+/CD56+ mycosis fungoides with cytotoxic marker expression: A variant with indolent course.

Mycosis fungoides is predominantly a disease of older patients, but occasionally occurs in children. We report a rare case of CD8+/CD56+ mycosis fungoides with cytotoxic marker (perforin, TIA-1, and granzyme B) expression in a 10-year-old boy. Disease presented with three asymptomatic, slowly progressive erythematous and scaling plaques, surrounded by hypochromic alone in the left tight and lower trunk. UVB narrow band associated with topical corticosteroids resulted in complete remission in about 2 months, and no recurrence at 2-year follow-up. Three similar cases have been retrieved in children through PubMed search, showing similar clinical presentation with erythematous scaling lesions, good response to skin-directed treatments and a favorable prognosis.

Primary Cutaneous CD4+ Small/Medium Pleomorphic T-Cell Lymphoproliferative Disorder: A Case Series.

BACKGROUND: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (CD4+ PCSM-LPD) is defined by a predominance of small- to medium-sized CD4+ pleomorphic T cells and a favorable clinical course. OBJECTIVE: We performed a retrospective analysis of 6 patients with CD4+ PCSM-LPD and reviewed the literature to address questions about its diagnosis, treatment, and prognosis. METHODS: Patients were 3 men and 3 women with a median age of 50 years. All patients presented with a single erythematous nodule, localised on the head in 4 patients and the upper trunk in 2 cases. No patients showed extracutaneous disease at any evaluation. Histopathologic features were characterised by nodular, diffuse, or, in 1 case, a superficial dense infiltrate of small/medium-sized pleomorphic CD4+/PD1+ T lymphocytes. T-cell receptor clonality was demonstrated in 5 cases. Treatment was surgical excision in 5 cases and radiotherapy in 1 case. RESULTS: All patients achieved complete resolution without relapses, during a median follow-up of 3 years. A review of the literature confirmed that CD4+ PCSM-LPD presents predominantly with a solitary nodular lesion on the face, neck, or upper trunk in adult patients. Surgical excision is the preferred treatment. Spontaneous resolution after biopsy may occur. CONCLUSIONS: CD4+ PCSM-LPD is a rare disorder with a favorable course.

Histiocytoid Sweet syndrome is infiltrated predominantly by M2-like macrophages.

BACKGROUND: Histiocytoid Sweet syndrome (HSS) is a rare variant of Sweet syndrome (SS). The nature of histiocytoid cells is still uncertain. OBJECTIVE: We sought to offer a comprehensive overview on clinical features of HSS and further information on immunohistochemical phenotype of the infiltrate. METHODS: The clinical, histologic, and immunohistochemical features of 12 of our patients with HSS and all cases retrieved through a PubMed search were analyzed. RESULTS: Lesions consisted of erythematous-violaceous papules and plaques, randomly distributed mostly on the trunk and the limbs. Three patients had myelodysplastic syndrome and 1 had a monoclonal gammopathy. The infiltrate was mainly composed of CD68(+)CD163(+)myeloperoxidase(+)myeloid cell nuclear differentiation antigen(+)CD117(-)CD15(-)CD34(-), a phenotype suggestive of M2-like macrophages. A few mature neutrophils and lymphocytes were also present. Review of all HSS cases showed no sex predominance and no extracutaneous infiltrates; inconstant presence of fever and blood neutrophilia; association with hematologic or solid neoplasms (26%), autoimmune conditions (12%), and infectious diseases (10%); and good response to steroid treatment, with rare relapses or recurrences. LIMITATIONS: The study includes a limited case series. The pathogenesis of the disease remains to be clarified. CONCLUSIONS: HSS lesions are infiltrated mostly by M2-like macrophages. The clinical features present more similarities than differences with SS.

Annular Lichenoid Dermatitis of Youth: Report of Six New Cases with Review of the Literature.

BACKGROUND: Annular lichenoid dermatitis of youth (ALDY) is an uncommon disease clinically reminiscent of morphea, annular erythema or mycosis fungoides. OBJECTIVE: To describe the histological and clinical features of a small series of patients with ALDY and to review the literature. PATIENTS: We describe the clinical and histological features of six patients (age range 7-79 years) with asymptomatic erythematous macules and patches with a red-brownish border and central hypopigmentation, mostly distributed on the groin and flanks. Histologically, all cases showed lichenoid dermatitis limited to the tips of rete ridges, with many intraepidermal CD8+ and some CD4+ T cells. T cell receptor rearrangement was absent in all cases. A total of 44 patients with a consistent clinical and histological picture have been described. The disease is sensitive to topical and/or systemic corticosteroids. CONCLUSIONS: ALDY is a unique lichenoid dermatitis for whose diagnosis a clinical-pathological correlation is essential. The disease typically affects young patients, more rarely adults and elderly.

A rare case of granuloma annulare in a 5-year-old child with type 1 diabetes and autoimmune thyroiditis.

Granuloma annulare (GA) has rarely been reported in childhood, and its etiology still remains unclear. Its association with type 1 diabetes (T1D) and other chronic systemic diseases such as autoimmune thyroiditis (AT) or rheumatoid arthritis has been reported. There is no description in the literature of pediatric cases and the simultaneous association of GA and multiple autoimmune diseases in the same subject. We report the case of a 5-year-old girl who presented onset signs and symptoms of T1D. The diagnosis of T1D was confirmed by the presence of autoimmune T1D antibodies. Moreover, AT was also diagnosed by autoantibodies and positive ultrasound. One month later, coin-size erythematous lesions appeared initially on the trunk but soon spread over the body. Once dermatophytosis had been excluded, a skin biopsy confirmed a diagnosis of GA. Although a clear mechanism remains still unknown, clinicians must take into consideration an association of GA in patients with T1D or AT to avoid unnecessary medical investigations and/or inadequate pharmacological treatment.

Recurrent cutaneous eosinophilic vasculitis characterized by annular purpuric lesions: A case report.

A 71-year-old woman presented with a persistent, intensely pruritic cutaneous eruption localized on the palmoplantar regions, lips and palate. The histological findings allowed to make the diagnosis of recurrent cutaneous eosinophilic vasculitis, a very rare cutaneous vasculitis characterized clinically by multiple erythematous or purpuric erythematous papules or plaques or angioedema with a relapsing course in the absence of systemic involvement and histologically by a necrotizing vasculitis of the dermal small vessels with a dominant eosinophilic infiltration. The patient was treated with oral methylprednisolone and pentoxifylline which led to a rapid resolution of the cutaneous lesions.

Exceptional Response in BRAF p.V600E-Mutant Enteric-Type Adenocarcinoma of the Lung With Cutaneous Spread: A Case Report.

Background: Enteric-type adenocarcinoma of the lung (lung-ETAC) is a rare form of lung cancer with histologic similarities to colorectal cancer, with aggressive behavior and unfavorable prognosis. Case Presentation: An 81-year-old man presented with discolored skin lesions on the chest and abdomen. After comprehensive evaluation, including skin biopsy and molecular profiling, the patient was diagnosed with having lung-ETAC with a BRAF p.V600E mutation. Treatment with dabrafenib and trametinib initially resulted in positive results, with improvement in skin lesions and overall clinical condition. Nevertheless, approximately 6 months after, the disease had progression with new skin lesions reappearing. Conclusions: We reported a unique case of a patient with BRAF p.V600E-mutant lung-ETAC with metastatic skin lesions achieving complete cutaneous response after targeted treatment with dabrafenib and trametinib, highlighting the potential for targeted therapy in patients with lung-ETAC harboring a BRAF p.V600E mutation.

Uncommon Non-Infectious Annular Dermatoses.

Several cutaneous diseases can present with annular lesions, making a distinction by physical appearance alone challenging. They can be distinguished into infectious and non-infectious, and common and uncommon annular dermatoses. Common non-infectious diseases include granuloma annulare, urticaria, and subacute lupus erythematosus. In addition, there are rare non-infectious non-neoplastic annular dermatoses whose nosographic attribution is established, including annually recurring erythema annulare centrifugum (EAC) and annular erythema in Sjögren syndrome and others whose nosographic positioning is still debated. They are neutrophilic figurate erythema, palpable migratory arciform erythema, eosinophilic annular erythema, and annular lichenoid dermatitis of youth. Their etiopathogenesis is largely unknown, although immune-mediated mechanisms are likely involved. It is difficult to establish if they are variants of reaction patterns or separate clinic-pathological entities. In fact, EAC and annually recurring EAC may represent different aspects of the same disease. Palpable migratory arciform erythema is hardly distinguishable from EAC deep type, Jessner-Kanof disease, and lupus tumidus. Neutrophilic figurate erythema and eosinophilic figurate erythema are clinically very similar and differing only in the relative proportion of eosinophils and neutrophils.

A Disseminated Mycobacterium Abscessus Infection in a Patient Affected by Pulmonary Graft versus Host Disease: Case Report with a Revision of Literature.

Mycobacterium abscessus complex, hereinafter Mab, is a taxonomic group of rapidly growing, nontuberculous mycobacteria (NTM). Despite major advances in understanding virulence, pathogenicity and mechanism of antibiotic resistance, Mab remains a significant cause of pulmonary and extra-pulmonary disease. Herein, we describe a disseminated, macrolide-resistant, Mab subspecies abscessus infection occurring in a severely immune-compromised 34-year-old allotransplanted female patient affected by pulmonary chronic graft versus host disease (cGVHD). The infection was characterized by hematogenous spread, and besides lungs, it involved skin, and soft tissues, resulting in a highly debilitating, painful, and finally fatal disease. Our case describes the severe impact of Mab infections in the setting of allogeneic hematopoietic stem cells transplant (alloHSCT) and related complications. It also highlights the unmet need of preventive and surveillance measures together with the urgency of developing effective vaccines and drugs against emerging NTM. The scarce literature regarding Mab infections in alloHSCT patients is also reviewed.

Leprosy initially misdiagnosed as sarcoidosis, adult-onset still disease, or autoinflammatory disease.

Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. We describe the case of a 20-year-old man from India living in Italy since 2003, who presented with erythematous papules and nodules distributed on his arms, legs, and face in 2006. He also had episodes of high fever, polyarthritis, and episcleritis. Sarcoidosis was suspected on the basis of elevated angiotensin-converting enzyme and bronchoalveolar lavage fluid, and the patient was treated with corticosteroids for about a year. A flare of the disease occurred each time corticosteroid was tapered or suspended. An autoinflammatory disease was then suspected and treated with immunosuppressant. Only the third deep skin biopsy revealed the presence of M. leprae. The lack of clinical suspicion and the unfamiliarity with the histology of leprosy delayed diagnosis and treatment. Leprosy should be considered in the differential diagnoses of patients presenting with rheumatic and cutaneous manifestations especially when they come from countries where the disease is endemic.

Annually Recurring Erythema Annulare Centrifugum: A New Case Series with Review of the Literature.

Annually recurring erythema annulare centrifugum (AR-EAC) is a rare variant, characterized by typical annular plaques recurring in the same period of the year. We describe 5 new cases and present a review of the literature. Patients were 3 females and 2 males with an age range of 25-55 years. Multiple annular plaques were located at the thighs in 4 patients and the neck in one patient. In 1 patient, a single lesion was present. Plaques were recurring in summer in 3 cases; in 1 case, in spring; and another patient, in winter since 3-4 years. Lesions were self-healing in few days or weeks. Histologically, the epidermis presented mild acanthosis with patchy spongiosis, slight parakeratosis, and mild exocytosis. There was a perivascular lympho-histiocytic infiltrate of variable intensity in the superficial dermis, with occasional eosinophils. In 1 case, the inflammatory infiltrate reached the deep dermis. Mucin deposition was absent. Phenotyping studies in 1 case revealed a predominance of T cells, with a small B-cell component. Moreover, a moderate number of CD123+ plasmacytoid dendritic cells and CD1a+ dendritic cells were noted. Fourteen cases of AR-EAC have been published previously. Collectively, patients' age ranged from 16 to 83 years, with a mean age of 47 years and a disease duration of 1-30 years. Lesions affected more frequently extremities and recurred most commonly in summer. Patients were all in good general health. Topical corticosteroids were the mainstay of treatment. AR-EAC is a benign disorder, the nature of which remains enigmatic.