Excerpt from Adiposis Dolorosa

Please click here to view the full topic text: Adiposis Dolorosa

Background

First described in 1892 by the American neurologist Francis Xavier Dercum at Jefferson Medical College in Philadelphia, PA, Dercum disease is an unusual progressive syndrome of unknown etiology characterized by multiple painful lipomas that arise in adult life, most often affecting postmenopausal women who are obese (Dercum, 1892). The onset is insidious. The pain is out of proportion to the physical findings and is often described by patients as "all fat hurts." The pain increases with increases in fatty tissue and in connection with menstruation. Estrogen replacement at menopause does not reduce the pain.

Since the original description of this disease, the clinical spectrum has changed to include, in addition to the painful nodular fatty deposits, other components of adiposis dolorosa. General obesity; fatigability; weakness; and a wide variety of unexplained emotional disturbances, such as depression, confusion, and dementia, are reported. This observation is why Dercum disease has been proposed to be relabeled as Dercum syndrome (Palmer, 1981).

Adiposis dolorosa is a disease that has been classified by the World Health Organization (WHO), and a paraphrase from the National Organization of Rare Diseases (NORD) says "Dercum Disease is a rare disorder in which there are fatty deposits which apply pressure to the nerves, resulting in weakness and pain. Various areas of the body may swell for no apparent reason. The swelling may disappear without treatment, leaving hardened tissue or pendulous skin folds."

Criteria for diagnosis

This syndrome consists of 4 cardinal symptoms: (1) multiple, painful, fatty masses; (2) generalized obesity, usually in menopausal age; (3) asthenia, weakness, and fatigability; and (4) mental disturbances, including emotional instability, depression, epilepsy, confusion, and dementia (Brodovsky, 1994).

Associated conditions

Associated conditions include sleep disturbances and pickwickian syndrome; slight-to-moderate dryness of the eyes and the mouth, with a gritty feeling in the eyes in spite of normal tear production (the criteria for Sjögren syndrome are not completely satisfied); an irritable bowel; coccygodynia; vulvovaginitis; vulvodynia; carpal tunnel syndrome; Tietze syndrome; chondromalacia patellae; thyroid malfunction, mainly hypothyreosis; trochanteritis; localized tendonitis; and onset of fibromyalgia (sometimes) (Greenbaum, 1991; Skagen, 1986).

Mode of inheritance

Dercum disease is believed to be transmitted in an autosomal dominant manner (Lynch, 1963; Cantu, 1973); it is particularly strong in the line of great grandmother-mother-daughter; however, most reported cases of adiposis dolorosa are sporadic (Campen, 2001).

Pathophysiology

The understanding of the pathogenesis and mechanism of adiposis dolorosa remains unknown. The origin of the pain is obscure, and the disease is better known as a clinical entity rather than as a physiologic or metabolic process (Hakan, 1996). Fatty deposits cause nerve compression and result in weakness and pain.

A review of the histopathologic findings showed no consistent histologic abnormality in the adipose tissue that might distinguish these tumors from common sporadic lipomas (Campen, 2001). In theory, the sudden appearance of the disease together with the incidence of a slight increase in the number of inflammatory cells in the fat could point toward the disease being, in part, an immune defense reaction (Leites, 1972; Skagen, 1986). Some authors believe that the sympathetic nervous system may play a role in the origin and development of the pain (Hakan, 1996).

The report of a case of adiposis dolorosa developing in association with the use of high-dose corticosteroids and its resolution upon reducing the dose suggests a causal relationship. Therefore, alterations of fat metabolism induced by corticosteroid excess may play a role in the development of this syndrome (Greenbaum, 1991). An earlier study suggested that a defect in the synthesis of monounsaturated fatty acids may play a role in its development. Further studies are needed to support this hypothesis and to identify a specific biochemical defect (Blomstrand, 1971).

A primary disturbance of endocrine function has been proposed but not demonstrated (Nekrolog, 1931).

Recently, adiposis dolorosa was suggested to be an expression of familial multiple lipomas, which is an autosomal dominant disease characterized by multiple asymptomatic lipomas. This observation was derived by studying the family patterns of 2 siblings with adiposis dolorosa; findings suggested that the disease segregates in an autosomal dominant fashion with variable phenotypic expressivity, ranging from totally asymptomatic to extremely painful lipomas (Gamez, 1998).

Mutational analysis excluded the 8344A®G mitochondrial mutation seen in other patients with multiple lipomas (Campen, 2001; Gamez, 1998). The A®G transition at position 8344 in the tRNA ^lys gene of mitochondrial DNA has been described in the syndrome myoclonic epilepsy and ragged-red fibers (MERRF). A number of reports described the presence of multiple lipomas resembling those of multiple symmetrical lipomatosis in some members of pedigrees with MERRF harboring the 8344 tRNA mutation (Silvestri, 1992).

Recently, Gamez et al described an unusual syndrome characterized by maternally inherited multiple symmetrical lipomatosis in a pedigree harboring the 8344 mutation in the tRNA ^lys gene of mitochondrial DNA (Gamez, 1998). Although the probands in their study harbored this mutation and had sensory polyneuropathy, they lacked the typical neuromuscular manifestations of MERRF.

Frequency

United States

Adiposis dolorosa is rare.

Sex

This condition is 20 times more common in females who are postmenopausal, obese, or overweight than in other people. It can occur in individuals who are not obese. Sixteen percent are males.

Age

This condition occurs in persons aged 45-60 years. Rarely, it occurs in women younger than 45 years. Adiposis dolorosa is almost never seen in children.

Please click here to view the full topic text: Adiposis Dolorosa