Connective tissue diseases (e.g., systemic lupus erythematosus (SLE), systemic sclerosis) are systemic diseases with significant dermatologic and nephrologic effects. Specific dermatologic findings of these conditions are found in other chapters of this book. They are included here for a complete discussion of dyschromias.

SLE is a systemic connective tissue disease with a wide array of symptoms and signs. Cutaneous involvement is significant and 4 of the 11 diagnostic criteria of SLE are mucocutaneous findings (Table 8.2). Several eruptions of SLE have archetypal descriptions in which dyspigmentation is a prominent finding. The malar rash, classically described as the “butterfly rash,” consists of facial erythema across malar cheeks and bridge of the nose. In comparison, discoid lupus typically demonstrates areas of hyperpigmentation and depigmentation especially in darker skinned patients. Other cutaneous manifestations of SLE include periungual telangiectasia, oral mucosal hemorrhages, and a livedoid reaction pattern, most commonly found on the lower legs.

Multidisciplinary treatment approaches are best. From a dermatologic standpoint photoprotection is of utmost importance. Sun avoidance is optimal; however, daily use of a high sun protection factor sunblock should be recommended to those who cannot completely avoid the sun [2]. Skin directed therapy includes the use of potent topical steroids, with topical calcineurin inhibitors being second line topical therapy. First line systemic treatment involves the use of antimalarial drugs; hydroxychloroquine is most commonly used. Ocular toxicity is rare but baseline and follow-up retinal examinations are required to monitor for retinal toxicity; the risk of retinal toxicity may increase with cumulative dose. A more common side effect of hydroxychloroquine is an idiosyncratic development of hyperpigmentation. Other more aggressive treatment options for cutaneous lupus are beyond the scope of this chapter.

Treatment with angiotensin inhibitors and angiotensin II receptor antagonists has improved renal morbidity significantly [6]. Skin directed therapies remain unsatisfactory with limited efficacy (Fig. 8.1).

Fabry disease, an X-linked lysosomal storage disorder leads to accumulation of neutral glycosphingolipids in multiple organ systems including the kidney. It is caused by mutations in the α-galactosidase A gene. Patients present with characteristic skin findings of multiple reddish-brown papules in a classic bathing suit distribution. Macular angiomas may also be seen on the proximal extremities, palmar and plantar surfaces, periungually and on the vermillion border of the lips. Cutaneous vascular lesions can be treated with intense pulse light (IPL) and other vascular lasers to improve cosmesis [7].

Nephrogenic systemic fibrosis is a rare and relatively recently described skin disorder [8]. While the exact etiology is yet to be elucidated, it is associated with exposure to gadolinium based contrast agents used in magnetic resonance imaging in patients with renal insufficiency [8]. Initial cutaneous changes are symmetrical red or deeper colored papules and plaques on the lower extremities with progressive swelling and tightening of the skin. Later stage disease has an indurated peau d’orange appearance of the extremities often with associated hyperpigmentation. Fibrosis may also involve extracutaneous sites including the heart, lungs, and the skeletal muscle and the sclera which can have yellowish plaques. There is no known effective treatment. Therapy is usually directed at optimizing renal function. Other therapies, with limited success include phototherapy, extracorporeal photophoresis, sodium thiosulfate, and rapamycin. Physical therapy is an adjunctive modality highly recommended to maintain functional mobility in affected patients [2, 8, 9].