Further out into the fibrous shell there is a zone that contains T cells and plasma cells in association with blood vessels. The histology of pulmonary nodules are similar to that of subcutaneous nodules, with central necrosis surrounded by palisading macrophages and inflammatory infiltrate. Risk Factors
Rheumatoid nodules develop if a person currently has rheumatoid arthritis. However, not all people with rheumatoid arthritis develop rheumatoid nodules. Some risk factors for rheumatoid nodules for people with rheumatoid arthritis may include:
Smoking (strong association)
Elevated levels of serum rheumatoid factors
HLA-DRB1 gene (weak association)
Trauma to small vessels
Having severe rheumatoid arthritis
Taking Methotrexate over other arthritis drugs

Diagnosis
Differential diagnosis of rheumatoid nodules can be classified from localization, depth pathology, age of onset, persistence, rheumatoid factor, concomitant joint disease, and bone erosions. Diagnosis is typically determined clinically by a rheumatologist. Rheumatoid arthritis associated rheumatoid nodules are typically subcutaneous and occur at extensor sites. The onset typically starts in adulthood and presents with rheumatoid factors and bone erosions, and concomitant joint diseases. The pathology is characterized by central necrosis, palisading mononuclear cells, and perivascular lymphocytic infiltrations.Rheumatoid nodulosis is characterized by multiple subcutaneous nodules presenting with rheumatoid factors but an absence of joint complaints. The nodules are typically small and concentrated on the extensor sites of the hands and feet, sometimes accompanied by bone erosions. The onset typically starts in adulthood with a pathology similar to rheumatoid arthritis associated rheumatoid nodules.Benign rheumatoid nodules are often not associated with rheumatoid factors or concomitant joint diseases. They are typically found on the feet, scalp, and pretibial regions.
Primary dysmenorrhea usually begins within a year or two of menarche, typically with the onset of ovulatory cycles. Perimenstrual pain is often included as a component of premenstrual syndrome (PMS). Secondary dysmenorrhea is the diagnosis given when menstruation pain is a secondary cause to another disorder. Conditions causing secondary dysmenorrhea include endometriosis, uterine fibroids, uterine adenomyosis, and polycystic ovary syndrome. Rarely, congenital malformations, intrauterine devices, certain cancers, and pelvic infections cause secondary dysmenorrhea. If the pain occurs between menstrual periods, lasts longer than the first few days of the period, or is not adequately relieved by the use of non-steroidal anti-inflammatory drugs (NSAIDs) or hormonal contraceptives, this could be a sign for secondary causes of dysmenorrhea.When laparoscopy is used for diagnosis, the most common cause of dysmenorrhea is endometriosis, in approximately 70% of adolescents.Other causes of secondary dysmenorrhea include leiomyoma, adenomyosis, ovarian cysts, pelvic congestion, and cavitated and accessory uterine mass. Risk factors
Genetic factors, stress and depression are risk factors for dysmenorrhea. Risk factors for primary dysmenorrhea include: early age at menarche, long or heavy menstrual periods, smoking, and a family history of dysmenorrhea.Dysmenorrhea is a highly polygenic and heritable condition. There is strong evidence of familial predisposition and genetic factors increasing susceptibility to dysmenorrhea. There have been multiple polymorphisms and genetic variants in both metabolic genes and genes responsible for immunity which have been associated with the disorder.Three distinct possible phenotypes have been identified for dysmenorrhea which include "multiple severe symptoms", "mild localized pain", and "severe localized pain".