February 2005

DIAGNOSIS: Hypertrichosis Lanuginosa Acquisita (Malignant Down)

TREATMENT AND RESPONSE: A CT scan performed in July, 2004 showed the recent development of a pleural effusion and a small pericardial effusion, as well as two cystic areas in the head of the pancreas, possibly consistent with pancreatic pseudocysts. The patient is currently refusing further treatment or malignant workup. Topical therapy with Epi-Stop and Vaniqa was initiated, and the patient reports diminished hair growth.



DISCUSSION: Lanugo hairs are normally present from the third month of fetal life through the end of gestation and are shed almost completely before birth (1). The reappearance of these hairs in adulthood, known as hypertrichosis lanuginosa aquista (HLA), or "malignant down", has been reported most commonly as a cutaneous paraneoplastic sign of internal malignancy. This disorder is characterized by the progressive development of fine, unpigmented hairs, most often on the face, and occasionally on the trunk, axillae and extremities, giving the patient a woolly appearance (2). Distribution and appearance of the hairs allow clinical differentiation from hirsutism. Histopathologic studies indicate that the follicles contain immature sebocytes within the mantle epithelium and may be arranged either parallel or perpendicular to the epidermal surface (3). Associated symptoms include glossitis, hypertrophy of tongue papillae, disturbances of taste and smell, and, less frequently, diarrhea, lymphadenopathy, and weight loss. The majority of cases have been reported in women between the ages of 40-70 (2).
The pathogenesis of HLA is unknown. Multiple authors have hypothesized that humoral mediator produced by the tumor is likely responsible; however, efforts to identify such a factor have been unsuccessful. Hormonal and biochemical studies in reported cases have not yielded any consistent abnormalities. HLA has not been exclusively linked to a specific type of malignancy. The most frequently associated cancer types include pulmonary squamous cell carcinoma, breast and uterine adenocarcinomas, colorectal carcinoma, lymphoma, and bladder carcinoma; however, there are reports of HLA in patients with a widely diverse group of neoplasms including malignant melanoma, gallbladder carcinoma, pancreatic carcinoma, and, most recently, extraskeletal Ewing's sarcoma. Though less common, HLA has also been observed in association with non-malignant conditions such as anorexia nervosa, AIDS, thyrotoxicosis, shock, porphyrias, and drugs including cyclosporine, streptomycin, penicillin, phenytoin, spironolactone, diazoxide, minoxidil, interferon, and corticosteroids (2,4,5). There is no specific treatment available for HLA; recently Vaniqa cream (eflornithine) which acts by inhibiting ornithine decarboxylase in the hair follicle, and laser hair removal with the Q-switched Nd:YAG laser have been used (6).
The temporal relationship between the appearance of HLA and the detection of an associated malignancy is incredibly variable. Symptoms of HLA may predate tumor detection by up to 2.5 years or may follow by as long as 5 years (2). The latest case report describes a patient in whom no malignancy was detected until one year following appearance of hypertrichosis, despite aggressive screening including CXR, abdominal US, mammography, endoscopy, hysteroscopy, laparoscopy, bone and thyroid scan, and measurement of CEA, C19-9, and C125 (5). Thus, HLA may be the presenting sign of an internal malignancy. It is important that patients with HLA who do not have a previously diagnosed malignancy, and in whom non-malignant causes have been ruled out, undergo comprehensive screening and careful monitoring to detect any associated neoplasm.


REFERENCES
1) Hovenden AL. Acquired hypertrichosis lanuginosa associated with malignancy.
Arch Intern Med. 1987 Nov;147(11):2013-8

2) Hovenden AL. Hypertrichosis lanuginosa acquisita associated with malignancy.
Clin Dermatol. 1993 Jan-Mar;11(1):99-106

3) Ikeya T, Izumi A, Suzuki M. Acquired hypertrichosis lanuginosa.
Dermatologica. 1978;156(5):274-82.

4) Farina MC, Tarin N, Grilli R, Soriano ML, Sarasa JL, Martin L, Requena L. Acquired hypertrichosis lanuginosa: case report and review of the literature.
J Surg Oncol. 1998 Jul;68(3):199-203

5) Perez-Losada E, Pujol RM, Domingo P, Matias-Guiu X, Lenti J, Lopez-Pousa A, Alomar A. Hypertrichosis lanuginosa acquisita preceding extraskeletal Ewing's sarcoma.
Clin Exp Dermatol. 2001 Mar;26(2):182-3.

6) Littler CM. Laser Hair removal in a patient with hypertrichosis lanuginosa congenita. Dermatol Surg. 1997. Aug; 23(8): 705-7.

7) Freedberg et al., Fitzpatrick's Dermatology in General Medicine (1999), p. 2115.

This case was presented by Kara Sternhell, Larry Wang, MD/PhD, and Jason Fung, MD