Adiposis Dolorosa

Description

Adiposis dolorosa, also known as Dercum disease, is characterized by generalized obesity and pronounced, disabling, and chronic pain in the adipose tissue of the proximal extremities, trunk, pelvic area, and buttocks; the face and hands are usually spared. There are a number of associated symptoms, including multiple lipomas, generalized weakness, fatigue, sleep disturbances, constipation, and psychiatric abnormalities. It is 5 to 30 times more common in women than men, and usually presents between 35 and 50 years of age (summary by Campen et al., 2001; review by Hansson et al., 2012).

Based on a review of the literature and studies of 111 patients, Hansson et al. (2012) proposed a classification of Dercum disease into 4 types: (I) generalized diffuse form without clear lipomas, (II) generalized nodular form with multiple lipomas, (III) localized nodular form, and (IV) juxtaarticular form with solitary fatty deposits near joints.

Clinical Features

This disorder, which was first described by Dercum (1892), is characterized by painful subcutaneous lipomas in a background of obesity. Severe asthenia has been emphasized as a feature by some (Wohl and Pastor, 1938).

Campen et al. (2001) reported a family in which 9 individuals spanning 2 generations had highly variable manifestations of lipomatosis. Seven individuals were studied in detail. The most severely affected male proband presented with over 20 painful lipomas on the abdomen, back, buttocks, and extremities, with onset at age 25 years. Another sister had 4 painful lipomas on the arm, also with onset at age 25. These 2 individuals were the only family members who reported pain associated with the lipomas; both were also obese, consistent with adiposis dolorosa. Both of these individuals reportedly had multiple birthmarks as children, and both were found to have several cafe-au-lait spots; 1 also had freckling. Obesity was present in many, but not all, affected relatives. One individual had only 1 painless lipoma on the patella that developed at age 39 years. Histopathologic analysis of the tumors from the 2 patients with painful lesions showed typical lipomas consisting of mature adipocytes. Entrapped nerves were not observed, and the tumors had well-defined margins. Genetic analysis excluded the mitochondrial DNA 8344A-G mutation in the MTTK gene (590060.0001), which has occasionally been found in patients with multiple symmetric lipomatosis (MSL; 151800). Campen et al. (2001) suggested that adiposis dolorosa may be an expression of MSL or familial multiple lipomas (FML; 151900).

In an extensive review of Dercum disease, Hansson et al. (2012) noted that several reports had described unusual symptoms, but it was unclear whether these were truly manifestations of the disorder. Some of these symptoms, such as tissue necrosis, hydronephrosis, and pain on the scalp or neck, may have resulted secondarily from compression of the fatty tissue on other structures.

Clinical Variability

Kyllerman et al. (2002) reported a 2-generation family in which a man and his 3 teenaged sons presented with variable neurologic abnormalities in early childhood. Features included dysarthria, disturbed ocular motility, rigidity, and delayed motor development. Brain imaging showed progressive bilateral cystic lesions in the putamen. The father developed painful lipomas on the trunk as an adult. His father reportedly had similar symptoms at the same age. The painful lipomas were reminiscent of Dercum disease, but neither the father, his father, nor 2 of his sons were obese; 1 son was described as 'slightly obese' at age 13 years. None of the sons had lipomas. Kyllerman et al. (2002) suggested that this family had a variant of Dercum disease, but Hansson et al. (2012) noted that it was unclear whether these patients truly fulfilled the diagnostic criteria.

Diagnosis

Hansson et al. (2012) suggested that the diagnostic criteria for Dercum disease should include generalized overweight or obesity and chronic pain in the adipose tissue present for over 3 months. The differential diagnosis is large and can include fibromyalgia, lipedema, panniculitis, lipomatosis, and endocrine abnormalities.

Inheritance

The majority of cases of Dercum disease occur sporadically (review by Hansson et al., 2012). However, there have been rare reports of familial occurrence consistent with autosomal dominant inheritance.

Lynch and Harlan (1963) observed the disease in 4 members of 3 generations of 1 family and in 2, possibly 4, persons in 2 generations of a second family.

Autosomal dominant inheritance was suggested by the families reported by Campen et al. (2001) and Cantu et al. (1973).