Héctor Fernández-Llaca

Long-term Successful Adalimumab Therapy in Severe Hidradenitis Suppurativa

BACKGROUND Several studies report the use of tumor necrosis factor alpha (TNF-alpha) inhibitors in refractory hidradenitis suppurativa (HS), particularly infliximab and etanercept. However, very limited data have been reported for adalimumab, the newest fully human anti-TNF-alpha monoclonal antibody. We evaluated the long-term efficacy and safety of adalimumab therapy in 6 patients with refractory HS. In the case of positive culture findings from any draining lesion, antibiotic therapy was administered for at least 2 weeks before initiating adalimumab therapy. Adalimumab (in 40-mg subcutaneous injections) was prescribed every other week. If the disease was inadequately controlled, the dosage was increased to 40 mg/wk. If HS was in persistent clinical remission, adalimumab therapy was gradually decreased to 40 mg every 3 weeks. Quality of life was assessed using the Dermatology Life Quality Index. OBSERVATIONS Six patients (mean [SD] age, 39.3 [12.9] years) with severe HS (mean [SD] duration, 22.5 [11.7] years) were treated with adalimumab. Significant improvements after 1 month of treatment were seen in the Dermatology Life Quality Index; in the number of affected regions, nodules, and fistulas; and in the basic laboratory findings. Improvements were maintained for a mean (SD) follow-up of 21.5 (7.1) (range, 13-29) months. Adalimumab was well tolerated. Conclusion Adalimumab appears to be an effective and safe treatment for refractory HS.

Henoch-Schönlein purpura in northern Spain: clinical spectrum of the disease in 417 patients from a single center.

AbstractThe severity of clinical features and the outcomes in previous series of patients reported with Henoch-Schönlein purpura (HSP) vary greatly, probably due to selection bias. To establish the actual clinical spectrum of HSP in all age groups using an unselected and wide series of patients diagnosed at a single center, we performed a retrospective review of 417 patients classified as having HSP according to the criteria proposed by Michel et al. Of 417 patients, 240 were male and 177 female, with a median age at the time of disease diagnosis of 7.5 years (interquartile range [IQR], 5.3–20.1 yr). Three-quarters of the patients were children or young people aged 20 years or younger (n = 315), and one-quarter were adults (n = 102). The most frequent precipitating events were a previous infection (38%), usually an upper respiratory tract infection, and/or drug intake (18.5%) shortly before the onset of the vasculitis. At disease onset the most common manifestations were skin lesions (55.9%), nephropathy (24%), gastrointestinal involvement (13.7%), joint symptoms (9.1%), and fever (6.2%). Cutaneous involvement occurring in all patients, mainly purpuric skin lesion, was the most common manifestation when the vasculitis was fully established, followed by gastrointestinal (64.5%), joint (63.1%), and renal involvement (41.2%). The main laboratory findings were leukocytosis (36.7%), anemia (8.9%), and increased serum IgA levels (31.7%). The most frequent therapies used were corticosteroids (35%), nonsteroidal antiinflammatory drugs (14%), and cytotoxic agents (5%). After a median follow-up of 12 months (IQR, 2–38 mo), complete recovery was observed in most cases (n = 346; 83.2%), while persistent, usually mild, nephropathy was observed in only 32 (7.7%) cases. Relapses were observed in almost a third of patients (n = 133; 31.9%).In conclusion, although HSP is a typical vasculitis affecting children and young people, it is not uncommon in adults. The prognosis is favorable in most cases, depending largely on renal involvement.

Urticarial vasculitis in northern Spain: clinical study of 21 cases.

AbstractUrticarial vasculitis (UV) is a subset of cutaneous vasculitis (CV), characterized clinically by urticarial skin lesions of more than 24 hours’ duration and histologically by leukocytoclastic vasculitis. We assessed the frequency, clinical features, treatment, and outcome of a series of patients with UV. We conducted a retrospective study of patients with UV included in a large series of unselected patients with CV from a university hospital. Of 766 patients with CV, UV was diagnosed in 21 (2.7%; 9 male and 12 female patients; median age, 35 yr; range, 1–78 yr; interquartile range, 5–54 yr). Eight of the 21 cases were aged younger than 20 years old. Potential precipitating factors were upper respiratory tract infections and drugs (penicillin) (n = 4; in all cases in patients aged <20 yr), human immunodeficiency virus (HIV) infection (n = 1), and malignancy (n = 1). Besides urticarial lesions, other features such as palpable purpura (n = 7), arthralgia and/or arthritis (n = 13), abdominal pain (n = 2), nephropathy (n = 2), and peripheral neuropathy (n = 1) were observed. Hypocomplementemia (low C4) with low C1q was disclosed in 2 patients. Other abnormal laboratory findings were leukocytosis (n = 7), increased erythrocyte sedimentation rate (n = 6), anemia (n = 4), and antinuclear antibody positivity (n = 2). Treatment included corticosteroids (n = 12), antihistaminic drugs (n = 6), chloroquine (n = 4), nonsteroidal antiinflammatory drugs (n = 3), colchicine (n = 2), and azathioprine (n = 1). After a median follow-up of 10 months (interquartile range, 2–38 mo) recurrences were observed in 4 patients. Apart from 1 patient who died because of an underlying malignancy, the outcome was good with full recovery in the remaining patients. In conclusion, our results indicate that UV is rare but not exceptional. In children UV is often preceded by an upper respiratory tract infection. Urticarial lesions and joint manifestations are the most frequent clinical manifestation. Low complement serum levels are observed in a minority of cases. The prognosis is generally good, but depends on the underlying disease.

Cutaneous diffuse large B‐cell lymphoma of the leg associated with chronic lymphedema

Development of malignant tumors is a rare but well known complication in chronic lymphedema (CL). We report herein a cutaneous diffuse large B‐cell lymphoma of the leg associated with CL. An 89‐year‐old man presented with multiple cutaneous lesions on his right limb that showed a CL. Dermatological examination disclosed multiple violaceous, firm, slightly infiltrated nodules on the anterior aspect of the leg and the dorsum and sole of the foot. A biopsy of one nodule of the leg disclosed a diffuse large B‐cell lymphoma, type of the legs. There was no evidence of lymphadenopathy on computed tomography (CT) scans of the chest, abdomen, and pelvis. A bone marrow aspiration and biopsy showed normal results. The patient was treated with local radiotherapy at a dose of 40 Gy, obtaining a highly significant, almost complete, clinical remission. A literature search identified 11 additional cases of primary cutaneous lymphoma associated with CL. An inadequate lymphatic drainage may make the lymphedematous region an immunologically vulnerable area, predisposing to neoplasia.

Posttransplant Kaposi’s Sarcoma Restricted to the Site of a Previous Deep Venous Thrombosis: Abrupt Onset after Withdrawal of Sirolimus

Kaposi’s sarcoma (KS) is an angioproliferative neoplasia associated with human herpesvirus 8 (HHV-8) infection. HHV-8 generates KS by means of the secretion of vascular endothelial growth factor (VEGF) andup-regulation of VEGF receptor, KDR, in endothelial cells. We report a case of KS in a 72-year-old male with a renal transplant who had received immunosuppressant drugs including sirolimus, mycophenolate mofetil, tacrolimus and steroids. KS developed 11 months after transplantation, in relation to deep venous thrombosis and withdrawal of sirolimus due to toxicity. Multiple purple papules and nodules were observed exclusively in the limb affected by thrombosis. Diagnosis of KS was confirmed by biopsy. Progressive withdrawal of prednisone was accompanied by full remission of the tumour. The thrombosis and withdrawal of sirolimus may have acted as cofactors in the development of KS, favouring the activation of the VEGF/KDR autocrine loop. Our experience contributes to further evidence that sirolimus may protect against KS.

Fibroepithelioma of pinkus with tumor giant cells.

A case of fibroepithelioma of Pinkus with pleomorphic epithelial giant cells is reported. The lesion was an ovoid polypoid nodule measuring 4 mm × 3 mm × 2 mm and was located close to the right axilla in an 86-year-old woman. The immunohistochemical features of the epithelial giant cells indicate that most of these cells are not cycling. We suggest that these cellular changes may represent a senescent event. Giant cells showed a mean nuclear major diameter more than twice that of small cells. Flow cytometric study of the tumor showed a hypodiploid DNA content and an intermediate grade S-phase fraction of the aneuploid component. To the best of our knowledge, a pleomorphic variant of Pinkus fibroepithelioma has not been reported to date. In fibroepithelioma of Pinkus, the correct diagnosis depends primarily on the architectural pattern of the tumor rather than on its cytologic features.

Drug-associated Cutaneous Vasculitis: Study of 239 Patients from a Single Referral Center

Objective. The 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitides defined drug-associated immune complex vasculitis as a distinct entity included within the category of vasculitis associated with probable etiology. In the present study we assessed the clinical spectrum of patients with drug-associated cutaneous vasculitis (DACV). Methods. Case records were reviewed of patients with DACV treated at a tertiary referral hospital over a 36-year period. A diagnosis of DACV was considered if the drug was taken within a week before the onset of the disease. Results. From a series of 773 unselected cutaneous vasculitis cases, 239 patients (30.9%; 133 men and 106 women; mean age 36 yrs) were diagnosed with DACV. Antibiotics (n = 149; 62.3%), mainly β-lactams and nonsteroidal antiinflammatory drugs (NSAID; n = 24; 10%) were the most common drugs. Besides skin lesions (100%), the most common clinical features were joint (51%) and gastrointestinal (38.1%) manifestations, nephropathy (34.7%), and fever (23.8%). The most remarkable laboratory data were increased erythrocyte sedimentation rate (40.2%), presence of serum cryoglobulins (26%), leukocytosis (24.7%), positive antinuclear antibodies (21.1%), anemia (18.8%), and positive rheumatoid factor (17.5%). Despite drug discontinuation and bed rest, 108 patients (45.2%) required medical treatment, mainly corticosteroids (n = 71) or immunosuppressive drugs (n = 7). After a median followup of 5 months, relapses occurred in 18.4% of patients, and persistent microhematuria or renal insufficiency in 3.3% and 5%, respectively. Conclusion. DACV is generally associated with antibiotics and NSAID. In most cases it has a favorable prognosis, although a small percentage of patients may develop residual renal damage.

Yellow Nails and Minimal Change Nephrotic Syndrome

We report a case of a 38-year-old man showing the yellow nail syndrome in association with minimal change nephrotic syndrome. Treatment with prednisone and vitamin E resulted in complete resolution of the nephrotic syndrome and slow improvement of the yellow nails, respectively. Although the rare yellow nail syndrome has been described in association with renal disease, this is the first report of the association of this syndrome with minimal change nephrotic syndrome.

Eosinophilic annular erythema in a patient with metastatic prostate adenocarcinoma.

References 1 Dervisoglu E, Akturk AS, Yildiz K, et al. The spectrum of renal abnormalities in patients with psoriasis. Int Urol Nephrol 2012; 44: 509–514. 2 Bagga A, Menon S, Hari P, et al. Nephrotic syndrome preceding psoriasis in child. Pediatr Nephrol 2007; 22: 1373–1376. 3 Wan J, Wang S, Haynes K, et al. Risk of moderate to advanced kidney disease in patients with psoriasis: population based cohort study. BMJ 2013; 347: f5961. 4 Donadio JV, Grande JP. IgA nephropathy. N Engl J Med 2002; 347: 738–748. 5 Wasilewska A, Zoch-Zwierz WM, Tenderenda E, et al. IgA nephropathy in a girl with psoriasis and seronegative arthritis. Pediatr Dermatol 2008; 25: 408–409. 6 Marocchi E, Spadaro A, Giannakakis K, et al. Infliximab in a patient with ankylosing spondylitis and secondary IgA nephropathy requiring haemodialysis. Clin Exp Rheumatol 2010; 28: 440. 7 Jacquet A, Francois H, Frangie C, et al. IgA nephropathy associated with ankylosing spondylitis is not controlled by infliximab therapy. Nephrol Dial Transplant 2009; 24: 3540–3542. 8 Sakellariou GT, Vounotrypidis P, Berberidis C. Infliximab treatment in two patients with psoriatic arthritis and secondary IgA nephropathy. Clin Rheumatol 2007; 26: 1132–1133. 9 Rosselli JL, Thacker SM, Karpinski JP, et al. Treatment of IgA nephropathy: an update. Ann Pharmacother 2011; 45: 1284–1296.

Erythema annulare centrifugum in a HIV‐positive patient

A 39-year-old man was referred on July 2003 for evaluation of an annular eruption on the trunk of 2 months’ duration. These lesions were slightly pruritic and had enlarged slowly since that time. The patient had had a medical history of previous intravenous drugs abuse between 1987 and 1994 and positive HIV infection since 1989. The patient has had no previous opportunistic infections. The patient had been receiving combined therapy with zidovudine, lamivudine, and indinavir since 1997 to present. Dermatological examination disclosed several well-circumscribed, erythematous annular lesions on the left thorax and lower part of the abdomen. These lesions had minimally elevated borders with delicate scaling on the advancing edges (Fig. 1). No other lesions were present on the skin or mucosa. Complete blood cell-count values revealed 2500/mm 3 leukocytes and 115,000/mm 3 thrombocytes. T-lymphocyte subsets revealed 189 CD4 and 458 CD8 lymphocytes/mm 3 . The HIV titer was < 50 RNA copies/mL. The remaining physical examination and routine laboratory data were otherwise unremarkable. A KOH examination from the material from the edge of the cutaneous lesions did not show any fungal elements. A punch biopsy revealed a superficial perivascular lymphohistiocytic infiltrate with a coat-sleeve distribution (Fig. 2a). The PAS staining was negative. Immunohistochemical phenotyping of the infiltrates was performed. The cells were mostly T lymphocytes (CD3) (Fig. 2b) and there was a preponderance of T cytotoxic/suppressor (CD8) to T helper/inducer cells (CD4). Positive staining for CD68 revealed a significant number of histiocytes. Erythema annulare centrifugum (EAC) of superficial type was diagnosed. Skin lesions were treated with topical corticosteroids, with progressive resolution in 4 weeks. After 2 months no skin lesions were present and the CD4 lymphocyte count was 519 cells/mm 3 . However, on June 2004, concomitant with a new descent of the CD4 (176 cells/mm3) (Fig. 3), new lesions of EAC developed on the trunk. These lesions resolved spontaneously in 3 weeks.