**Core Concept**
Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the axial skeleton, leading to eventual fusion of vertebrae and loss of spinal mobility. This condition is characterized by a complex interplay between genetic predisposition, immune system dysregulation, and environmental triggers.

**Why the Correct Answer is Right**
Ankylosing spondylitis is strongly associated with the HLA-B27 gene, with approximately 90% of patients being HLA-B27 positive. The exact mechanism by which HLA-B27 contributes to AS is not fully understood, but it is believed to involve the presentation of antigens to CD4+ T cells, leading to a chronic inflammatory response in the spine and sacroiliac joints. This inflammatory response ultimately results in the formation of new bone, leading to the characteristic fusion of vertebrae seen in AS.

**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because ankylosing spondylitis is primarily an axial disease, with the majority of patients experiencing symptoms in the spine and sacroiliac joints. While peripheral joint involvement can occur, it is less common.
**Option B:** This option is incorrect because while ankylosing spondylitis is associated with an increased risk of uveitis, this is not a universal feature of the disease. Uveitis occurs in approximately 20-30% of patients with AS.
**Option C:** This option is incorrect because while ankylosing spondylitis is a systemic disease, it is not typically associated with skin manifestations such as psoriasis or dermatitis herpetiformis.

**Clinical Pearl / High-Yield Fact**
A key clinical feature of ankylosing spondylitis is the presence of a "bamboo spine" on radiographs, which is characterized by the fusion of vertebrae and the formation of syndesmophytes. This finding is highly suggestive of AS and can be used to support the diagnosis.

**Correct Answer: D.**