Of all the skin diseases described in this article, dermatomyositis, along with autoimmune blistering diseases, is perhaps the one with the highest level of evidence for efficacy. Placebo-controlled studies2 and multiple case series3 have been published, reporting satisfactory outcomes. IVIG is indicated as first-line therapy in cases of dermatomyositis with severe muscular involvement (fulminant myolysis), inclusion body myositis, and polymyositis.4 Cases of juvenile dermatomyositis,5 idiopathic dermatomyositis, and paraneoplastic dermatomyositis have been described with good response to treatment. IVIG is administered as adjuvant therapy, never as monotherapy, in patients who have not responded adequately to systemic corticosteroids after 1 month or in patients who experience worsening of muscle symptoms on decreasing the corticosteroid dose. The posology is described in Table 2. These agents are also useful in the treatment of skin manifestations associated with dermatomyositis, particularly when these are severe and extensive, even when muscular involvement is not present,6 or in the treatment of dystrophic calcinosis7 and calcinosis refractory to multiple immunosuppressants.8 Good outcomes have also been reported in severe edematous dermatomyositis9 and in dermatomyositis panniculitis.10 According to the systematic review by Callander et al.,11 IVIG therapy is an interesting alternative in the treatment of amyopathic dermatomyositis, as reported in isolated cases.12 In the treatment of juvenile dermatomyositis, IVIG therapy occupies a position as an effective and safe alternative,13 particularly when administered subcutaneously.14 This route of administration represents a major breakthrough in terms of safety and low rate of side effects, and it also reduces the number of school days missed.

Autoimmune blistering diseases are the second group of diseases in which IVIG therapy is an interesting treatment alternative,15,16 particularly in the severe forms and forms refractory to systemic glucocorticosteroids in combination with immunosuppressants (azathioprine and mofetil mycophenolate). IVIG therapy in the field of autoimmune blistering diseases is considered second-line treatment, although severe cases of pemphigus vulgaris, pemphigus foliaceus, mucous membrane pemphigoid,17 and acquired epidermolysis bullosa18 have been published with good therapeutic response. Other indications with a lower level of evidence for the use of IVIG therapy are bullous pemphigoid, linear IgA disease, IgA pemphigus, and paraneoplastic pemphigus. Table 2 shows the posology of IVIG therapy in blistering diseases. However, the use of rituximab in this group of diseases has been a great advance in the treatment and outcomes in these patients, with long disease-free periods.19 In patients with recalcitrant disease, the combination of rituximab and IVIG therapy has been shown to be effective,20,21 with complete and sustained responses; however, given the high cost of this combination, patients who would benefit from this therapeutic option should be selected appropriately. In our hospital, experience with the combination of rituximab and IVIG therapy, although limited to a small number of patients, has been satisfactory in those cases refractory to first-line drugs, as well as their possible combinations.

In certain special situations, such as when systemic glucocorticosteroids are contraindicated (aseptic bone necrosis, difficult-to-control diabetes mellitus, and severe osteoporosis), IVIG therapy could be justified as first-line treatment. However, this should always be as an adjuvant to other drugs such as immunosuppressants or rituximab, never as monotherapy. Good response to treatment can be assessed by the absence of new lesions and epithelization of existing ones, along with decreased autoantibody titers (IgA measured by enzyme-linked immunosorbent assay) or the possibility of reducing the dose of systemic glucocorticosteroids without disease deterioration.

IVIG therapy can also be indicated in gestational pemphigoid, a special situation given the therapeutic limitations associated with pregnancy, particularly when administration of glucocorticosteroids does not achieve sufficient disease control. The effectiveness of IVIG administration in cases of refractory gestational pemphigoid has been reported in several articles,22,23 in association with oral cyclosporin24 or as monotherapy,25 without any side effects for the neonate.

Among the vasculitis syndromes, Kawasaki disease is the only one in which IVIG is considered first-line therapy.26 Perhaps the most difficult aspect of this process is initial suspicion, as the patient may not meet all diagnostic criteria and therefore there is a delay in administration of treatment. The posology is described in Table 2. Some authors suggest IVIG administration as a single perfusion for 10-12hours, always in combination with acetylsalicylic acid. There are predictive factors for resistance to IVIG therapy,27 the most relevant currently being level of C-reactive protein (CRP) before starting treatment.28 The aim of treatment is to avoid formation of coronary aneurysms and associated comorbidities (ischemia, rhythm disorders, etc.). Decreased levels of CRP in plasma are the best indicator of good response to treatment.

Toxic epidermal necrolysis (TEN) is a severe toxicoderma with a mortality as high as 40% according to some published series. Apoptosis of keratinocytes is mediated by the action of Fas (CD95), granulysin, and annexin-1. Rapid identification of the process, withdrawal of the suspected causal drug, and admission to the intensive care unit for care of the patient as if they had severe burns are essential for improving the chance of survival. Several meta-analyses and systematic reviews have been published on the pharmacological treatment of TEN, given that major controversy exists as to the efficacy of administration of immunosuppressants during admission to hospital. The most recent clinical practice guidelines for TEN29 confer IVIG therapy an important role if administered early at high doses (3mg/kg), as a single cycle, split over 3 days at a slow infusion speed. It is essential to be aware of the patient¿s comorbidities, in particular renal insufficiency, cardiovascular diseases, and diabetes mellitus,30 as fractioning the dose over 3 to 5 days avoids decompensation due to fluid overload. The best sign for detecting suitable response to treatment is absence of epidermal detachment, as well as the start of re-epithelization of previously affected areas. Although numerous drugs have been used to treat this often fatal disease, basic skin and mucosal care, control of vital signs, and maintaining a good fluid and electrolyte balance seem to be the only interventions that have been shown to improve patient survival.31

Scleromyxedema is a rare disease consisting of fibroblast proliferation and mucin deposition in the skin and internal organs, with resulting progressive hardening and fibrosis. It is usually a disease that is hard to treat, as it does not respond to multiple immunosuppressants and so is associated with high morbidity and mortality. In 2000, the first report appeared of good response to IVIG therapy.32 According to data published on patients with scleromyxedema with predominant neurocutaneous involvement, IVIG therapy is considered the treatment of choice, either alone or in combination with corticosteroids33 or plasmapheresis.34 The posology is described in Table 2. As with other dermatoses, factors predictive of good response to treatment correspond to skin changes, as well as improved function of internal organs.

IVIG therapy can be considered as a treatment option in patients with severe pyoderma gangrenosum refractory to normal treatment (systemic glucocorticosteroids and oral cyclosporin A). The only reports correspond to single cases or small case series,35–37 all with severe pyoderma gangrenosum and good outcomes. It is recommended to administer IVIG therapy as an adjuvant to systemic glucocorticosteroids and/or cyclosporin A, although some cases of administration as monotherapy have been reported.

Livedoid vasculopathy presents with painful ulcers, above all on the legs, and these have a major impact on the patient¿s quality of life. The lesions can be refractory to multiple treatments. IVIG therapy has been used in severe difficult-to-treat cases with good response to treatment, according to published series.38–40 IVIG therapy is increasingly seen as a treatment option in this difficult-to-treat disease.