Follicular Eruption With Folliculotropic Lymphocytic Infiltrates Associated With Iatrogenic Immunosuppression: Report and Study of 3 Cases, and Review of the Literature.

BACKGROUND: Several cases of folliculotropic mycosis fungoides, associated with immunosuppressive therapy, including calcineurin inhibitors, have been reported in solid organ transplant patients. We have encountered 3 patients on immunosuppressive therapy who developed follicular eruptions with folliculocentric infiltrates of nonatypical lymphocytes. OBJECTIVE: To characterize these follicular eruptions and review the literature. METHODS: Three patients, aged 7-15 years, who were treated with systemic immunosuppressive therapy developed follicular eruptions characterized histopathologically by folliculocentric lymphocytic infiltrates. These were studied clinically, histopathologically, immunophenotypically, and molecularly for T-cell receptor (TCR) gene rearrangement. RESULTS: All 3 cases were characterized histopathologically by folliculocentric infiltrates of nonatypical CD3 T lymphocytes with variable follicular exocytosis. Two cases also showed follicular mucinosis. Marked reduction in CD7 staining, and marked predominance of CD4 cells over CD8 cells was observed in all 3 cases. The TCR gene rearrangement studies were monoclonal in 2 cases. Oral calcineurin inhibitors (2 cyclosporine A and 1 tacrolimus) were part of the therapeutic regimen in all 3 patients. Their cessation along with local corticosteroid creams in 2 patients, and phototherapy with oral acitretin in one patient, was associated with complete clinical remission. CONCLUSIONS: Patients undergoing systemic immunosuppressive therapy that includes calcineurin inhibitors might develop follicular eruption with some immunophenotypical variations and a monoclonal TCR gene rearrangement but lack sufficient cytomorphological features of folliculotropic mycosis fungoides. Altering the immunosuppressive agent including calcineurin inhibitors may result in regression of the eruptions.

Clinical and microbiological properties of Staphylococcus lugdunensis skin infections.

Staphylococcus lugdunensis is an emerging pathogen in skin and soft tissue infections that was previously considered a commensal. The aim of this study was to elucidate the characteristics of skin infections by S. lugdunensis and its appropriate management, in a tertiary referral medical center. The clinical files, bacterial cultures and histopathology reports of all S. lugdunensis isolates from skin infections over a period of 8 years (September 2009-September 2017) were reviewed. S. lugdunensis was isolated from 29 patients with skin infections, aged 7-89 years (mean 33.3 years). A state of immune suppression (drug-induced, malignancy or diabetes) was present in five patients (17%). Folliculitis and cutaneous pustulosis were the most common presentations (16 cases, 55%), followed by secondary infection of hidradenitis suppurativa (five cases, 17%). Other sources of isolation were infected molluscum contagiosum (two cases), folliculitis decalvans (one case), dissecting cellulitis (one case), abscess (one case), cyst (one case), impetigo (one case) and granuloma after trauma (one case). The in vitro antibiotic sensitivity tests showed susceptibility to most tested antibiotics, although a few isolates were resistant to gentamycin, penicillin and oxacillin. In 19 of 20 patients for whom follow ups were available, cutaneous manifestations improved or resolved with proper local and/or oral antibiotic therapy. S. lugdunensis may play a role as a primary or secondary pathogen in various skin infections, most commonly folliculitis and pustulosis. Proper antibiotic therapy may lead to improvement or resolution.

Large leg ulcers due to autoimmune diseases.

BACKGROUND: Large leg ulcers (LLU) may complicate autoimmune diseases. They pose a therapeutic challenge and are often resistant to treatment. To report three cases of autoimmune diseases complicated with LLU. CASE REPORT: Case 1. A 55-year old woman presented with long-standing painful LLU due to mixed connective tissue disease (MCTD). Biopsy from the ulcer edge showed small vessel vasculitis. IV methylprednisolone (MethP) 1 G/day, prednisolone (PR) 1mg/kg, monthly IV cyclophosphamide (CYC), cyclosporine (CyA) 100mg/day, IVIG 125G, ciprofloxacin+IV Iloprost+enoxaparin+aspirin (AAVAA), hyperbaric oxygen therapy (HO), maggot debridement and autologous skin transplantation were performed and the LLU healed. Case 2. A 45-year old women with MCTD developed multiple LLU's with non-specific inflammation by biopsy. MethP, PR, hydroxychloroquine (HCQ), azathioprine (AZA), CYC, IVIG, AAVAA failed. Treatment for underlying the LLU tibial osteomyelitis and addition of CyA was followed by the LLU healing. Case 3. A 20-year-old man with history of polyarteritis nodosa (PAN) developed painful LLU's due to small vessel vasculitis (biopsy). MethP, PR 1 mg/kg, CYC, CyA 100 mg/d, AAVAA failed. MRSA sepsis and relapse of systemic PAN developed. IV vancomycin, followed by ciprofloxacin, monthly IVIG (150 g/for 5 days) and infliximab (5 mg/kg) were instituted and the LLU's healed. CONCLUSIONS: LLU are extremely resistant to therapy. Combined use of multiple medications and services are needed for healing of LLU due to autoimmune diseases.

Insulin-like growth factor-binding protein 7 regulates keratinocyte proliferation, differentiation and apoptosis.

Insulin-like growth factor (IGF)-binding protein 7 (IGFBP7) belongs to the IGFBP superfamily, which is involved in the regulation of IGF and insulin signaling. Recently, a global gene expression study revealed that IGFBP7 is downregulated in the psoriatic epidermis, with UVB phototherapy restoring its expression to normal. In the present study, we confirmed that IGFBP7 expression is decreased in psoriatic lesions. Given the previous data suggesting a role for IGFBP7 in the control of cancer cell growth, we investigated its involvement in the regulation of keratinocyte (KC) proliferation and differentiation, which are abnormal in psoriasis. To model IGFBP7 downregulation in vitro, we used IGFBP7-specific small interfering RNA or small hairpin RNA-expressing lentiviral vectors in HaCaT cells or primary human KCs. Downregulation of IGFBP7 was found to markedly enhance KC proliferation in both systems, was associated with a significant decrease in KC susceptibility to tumor necrosis factor-alpha-induced apoptosis, but did not affect senescence. Downregulation of IGFBP7 was also shown to block expression of genes associated with calcium-induced differentiation of human KCs. Finally, recombinant IGFBP7 was found to inhibit KC proliferation and enhanced their apoptosis. These data position IGFBP7 as a regulator of KC proliferation and differentiation, suggesting a potential role for this protein in the pathophysiology and treatment of hyperproliferative dermatoses such as psoriasis.

Low dose methotrexate therapy is effective in late-onset atopic dermatitis and idiopathic eczema.

BACKGROUND: Atopic dermatitis or atopic eczema is an itchy inflammatory skin condition with a predilection of the skin flexures. Most cases start in children although some have been reported in adults. Patients with moderate to severe disease refractory to topical corticosteroid or calcineurin inhibitors may require second-line treatment such as phototherapy or systemic immunosuppressants. Methotrexate therapy has been suggested as a useful immunosuppressant in adult atopic dermatitis. OBJECTIVES: To further determine the efficacy of low dose methotrexate therapy in adults with new-onset atopic dermatitis or with idiopathic eczema. METHODS: All adult patients with new-onset atopic dermatitis or idiopathic eczema treated by methotrexate in our clinics from 2004 to 2006 were included in the study. All had failed prolonged therapy with oral antihistamines and local corticosteroid creams. Methotrexate, 10-20 mg, was given orally once a week along with folic acid supplements 5 days a week. Additional therapies included predominantly emollients. During the entire treatment period the investigators made global assessments of the clinical response. RESULTS: Nine patients diagnosed with late-onset atopic dermatitis (n = 6) or idiopathic eczema (n = 3) were treated with methotrexate. All patients responded to the drug. The initial response was noted after 3-7 weeks. Six patients achieved complete remission after 3 months of methotrexate therapy and three patients had significant improvement. One patient's condition worsened after achieving a complete response while on methotrexate and the drug was withdrawn completely. No serious adverse events were noted during treatment. CONCLUSIONS: Low dose methotrexate is an effective therapeutic alternative for late-onset atopic dermatitis or idiopathic eczema in patients unresponsive to local and other systemic therapies.