Miki Shirakawa Garcia

The etiology of paraneoplastic autoimmunity.

Although they may sometimes appear similar, paraneoplastic autoimmunity has a unique pathogenesis, different from the classical autoimmune diseases not associated with cancer. When distinguished clinically, paraneoplastic autoimmunity is more severe and often presents with a broader range of clinical signs and symptoms. Management of these patients is difficult and is usually centered in part on treatment of the underlying malignancy. Self-antigens recognized in the setting of paraneoplastic autoimmunity can be diverse, and the number of determinants recognized within a single antigen can be numerous. This review uses prototypic examples of paraneoplastic immune-mediated diseases and their associated malignancies to describe the mechanisms by which immune dysregulation can occur in the setting of cancer. Specific diseases covered include paraneoplastic pemphigus, Sweet’s syndrome, pyoderma gangrenosum, thymoma-associated multiorgan autoimmunity, myasthenia gravis, autoimmune hemolytic anemia, immune thrombocytopenia, and the paraneoplastic neurological syndromes. The malignancies discussed include thymoma, non-Hodgkin’s lymphoma, and chronic lymphocytic leukemia, among others. The mechanisms by which cancers induce autoimmunity are broken down into the following categories: disruption of central tolerance, peripheral immune dysregulation, and alteration of self-antigens. For each category, examples of paraneoplastic autoimmune diseases and their associated malignancies are discussed. Finally, mechanisms by which cancer treatment can lead to autoimmunity and examples of polymorphisms that are linked to both cancer and autoimmunity are discussed.

Management of recalcitrant hidradenitis suppurativa with ustekinumab.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease resulting from occlusion of the pilosebaceous units within the intertriginous regions of the body. It is characterized by very tender papules, nodules, and neutrophilic abscesses. Sinus tracts with malodorous drainage and scarring can develop. Long-term complications include lymphoedema and fistulae formation. We present here a difficult case of HS that responded well to ustekinumab.

Biologic Therapies in the Treatment of Psoriasis: A Comprehensive Evidence-Based Basic Science and Clinical Review and a Practical Guide to Tuberculosis Monitoring

The treatment of psoriasis has undergone a revolution with the advent of biologic therapies including infliximab, etanercept, adalimumab, efalizumab, golimumab, certolizumab, alefacept, secukinumab, abatacept, and ustekinumab. These medications are designed to target specific components of the immune system and are a major technological advancement over traditional immunosuppressive medications. Herein, we present a comprehensive, unbiased comparison of these medications focusing on their differences. For example, TNF antagonists can differ in the way they are dissolved and administered, the effector molecules they can bind, serum peak and trough levels, the types of intracellular signals they can induce, the in vivo complexes that they can form, their protein structure, and their incidence and timing of rare adverse events, among other things. A critical review of the clinical studies that have tested the efficacy of these molecules is also presented including head-to-head comparison trials. The safety of biologics in terms of their long-term adverse events is discussed, as is their use in different types of psoriasis and in different patient populations. Finally, all anti-TNF agents have been associated with a variety of serious and “routine” opportunistic infections, particularly tuberculosis. For this reason, anti-tuberculosis testing both prior to the initiation of a biologic therapy and annually during treatment is pertinent. The uses and limitations of both the tuberculin skin test (TST) and QuantiFeron®-TB Gold (QFT) are discussed, as is the care of patients who present with latent tuberculosis infection prior to the initiation of biologic therapy. Recommendations for tuberculosis monitoring are provided.

Effective strategies for the management of pyoderma gangrenosum: a comprehensive review.

Pyoderma gangrenosum (PG) is an inflammatory disease characterized by painful skin ulcerations with undermined and erythematous borders. The etiology of PG is not well understood, but it is generally considered to be an aberrant immune response characterized by a dermal neutrophilc infiltrate. Given the existence of only a few PG clinical trials, treatment options are largely based upon anecdotal data and small case studies. In addition to classic immunosuppressive medications, PG has been reported to respond well to the anti-TNF agents, infliximab, etanercept, adalimumab. Newer biologics such as ustekinumab (anti-IL-23), ixekizumab (anti-IL-17) and brodalumab (anti-IL-17R) are promising given the effect of IL-17 on neutrophil migration. However, the effectiveness of these newer agents remains to be rigorously evaluated. Multi-drug regimens have not been well described in the literature but are an excellent alternative for patients with refractory disease. Herein, we provide a comprehensive review of the pathophysiology of PG and of the different treatments available for managing PG patients, including the theoretical benefit of initiating multidrug regimens. We also provide one possible treatment algorithm for patients with refractory disease and give examples of refractory PG cases successfully treated with multidrug regimens.

Complete regression of subcutaneous and cutaneous metastatic melanoma with high-dose intralesional interleukin 2 in combination with topical imiquimod and retinoid cream.

There are limited treatment options for metastatic melanoma, which is almost universally fatal. We report the successful treatment of 64 of 64 cutaneous and subcutaneous melanoma metastases in three patients using high-dose (22 million units per 1.2 ml) intralesional interleukin 2 (IL-2) in combination with topical imiquimod and a retinoid cream. Before intralesional therapy, all patients had been treated surgically and were no longer considered surgical candidates. Rebiopsy of 15 of the treatment sites and long-term follow-up (10, 12, and 27 months) showed regression of all treated tumors. Six months after discontinuation of therapy, one patient developed multiple new cutaneous metastases, but these were also responsive to treatment with intralesional therapy. The other two patients did not experience recurrence of their cutaneous melanoma. However, one of the two patients developed lymph node and brain metastases 18 months after initiation of intralesional therapy, but is still alive, now at 27 months. The concentration of IL-2 used for the intralesional therapy was much higher than in previously reported cases, which may explain the excellent responses that were observed. These results support intralesional high-dose IL-2 as a very effective therapy for controlling cutaneous metastatic melanoma. Additional studies are needed to determine whether this therapy is associated with a survival benefit.

Treatment of Dermatosis Papulosa Nigra in 10 Patients: A Comparison Trial of Electrodesiccation, Pulsed Dye Laser, and Curettage

BACKGROUND Dermatosis papulosa nigra (DPN) is a common variant of seborrheic keratoses in darkly pigmented individuals. Treatment options include cryosurgery, curettage, electrosurgery, and shave removal. OBJECTIVE To compare the efficacy and complications of pulsed dye laser (PDL) therapy for the treatment of DPN with those of curettage and electrodesiccation. METHODS AND MATERIALS Randomized, controlled, single‐center, evaluator‐blinded trial of 10 patients with at least four clinically diagnosed lesions. RESULTS All 10 patients completed the study. Mean lesion clearance was 96% for curettage, 92.5% for electrodesiccation, and 88% for laser. There was no significant difference between the three treatment modalities. All three techniques had an overall cosmetic outcome of good for most patients. Five of the 10 patients preferred electrodesiccation. Patients rated the laser as the most painful treatment method. The most common adverse outcome was hyperpigmentation. There were no significant differences between the treatment groups for any of the measured outcomes. CONCLUSION The efficacy of PDL in the treatment of DPN is not significantly different from the already established treatment modalities of electrodesiccation and curettage. &NA; The authors have indicated no significant interest with commercial supporters.

Familial facial papules. Birt-Hogg-Dubé syndrome.

What is your diagnosis?

Familial facial papules: Familial facial papules

What is your diagnosis?

Familial facial papules

What is your diagnosis?