Dermatologic Manifestations of Hermansky-Pudlak Syndrome Clinical Presentation

Updated: Dec 13, 2019
  • Author: Jaclyn Scholtz, MD; Chief Editor: Dirk M Elston, MD  more...
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Because patients with Hermansky-Pudlak syndrome have platelet dysfunction, albinism, and ceroid accumulation, clinical history that relates to these complications must be investigated.

When the intestines accumulate ceroid, patients can have diarrhea, weight loss, cramps, and possibly blood in the stool. These manifestations resemble those of inflammatory bowel disease, with the onset of symptoms occurring in patients aged 12-30 years. Response to medical therapy generally is poor. One article reported 2 children, aged 7 years and 3 years, with granulomatous colitis in association with Hermansky-Pudlak syndrome. [23] One of these children was Puerto Rican. Hazzan et al [24] noted Crohn disease–like colitis, enterocolitis, and perianal disease in a patient with Hermansky-Pudlak syndrome, suggesting that the intestinal pathology of Hermansky-Pudlak syndrome results from the development of classic Crohn disease.

Ceroid can accumulate in the pulmonary system as well. When the lungs are impaired in this fashion, shortness of breath and abnormal fatigue with exertion can occur. The disease can progress to pulmonary fibrosis, with scar tissue restricting the inflation of the lungs. [25] Patients should be asked about previous pulmonary function tests and steroid therapy. Thomas de Montpréville et al [26] noted pulmonary fibrosis in a patient with Hermansky-Pudlak syndrome related to a defect in surfactant. This patient had undergone lung transplantation.

Hermansky-Pudlak syndrome impairs vision; thus, patients should be asked about photophobia, previous eyeglasses, bifocals, eyeglass tints, low-vision aids, amblyopia therapy, and strabismus surgery.

Patients with Hermansky-Pudlak syndrome are prone to skin cancers; thus, they should be asked about any new skin lesions. A history of previous skin biopsies, skin cancer, sun exposure, and sunblock application should be obtained from patients.

Bleeding diathesis must be investigated. Persons with Hermansky-Pudlak syndrome may have a tendency to bruise easily or to experience frequent nosebleeds or prolonged bleeding. Epistaxis is the most frequent hemorrhagic manifestation. Patients with Hermansky-Pudlak syndrome can have unusual bleeding episodes (eg, heavy menstrual bleeding, bleeding with dental procedures). Patients should be asked about medications that affect bleeding and, thus, should be queried about the use of aspirin and aspirin derivatives. Persons should be asked if their children or parents bleed easily.

Women with Hermansky-Pudlak syndrome should be asked about pregnancies and pregnancy complications, menometrorrhagia, abnormal uterine bleeding, and gynecologic surgery. Therapy-refractory menorrhagia has been noted as the first manifestation of Hermansky-Pudlak syndrome. [27]

Family history is important in understanding Hermansky-Pudlak syndrome. Patients should be asked where their families originated. Puerto Rican ancestry is important and must be investigated. Parental consanguinity and family incidence of Hermansky-Pudlak syndrome need to be reviewed with patients.

In 2003, Iannello et al [28] described a new familial Hermansky-Pudlak syndrome clinical variant in 2 sisters, one aged 6 years and the other aged 23 years. They expressed the common symptoms of Hermansky-Pudlak syndrome, but they also had diffuse interstitial pulmonary disease as well as augmented platelet aggregation. Additionally, they were very susceptible to bacterial infections.

Interestingly, Iannello et al [28] observed a urinary tract abnormality in a younger sister with Hermansky-Pudlak syndrome and a porencephalic cyst in an older sister with Hermansky-Pudlak syndrome. These developmental defects have been reported in persons with Cross syndrome (oculocerebral hypopigmentation syndrome), which is a syndrome that has evaded precise definition. These sisters seemed to have an overlapping of the phenotypic manifestations of different rare syndromes. The presence of ceroidlike autofluorescent material in urinary sediment, combined with the histologic aspects and the autofluorescence of oral mucosa biopsy specimens, was consistent with a ceroidlike lipofuscin storage problem.

Enders et al [29] noted lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II.

Interestingly, Hermansky-Pudlak syndrome is a bleeding defect, in part, but late-onset menstrual bleeding has been noted. [30]

In Hermansky-Pudlak syndrome type IV, which involves (BLOC)-3, impacts healthy subjects' working memory and impacts function deficits in those with schizophrenia; this is not surprising because HPS is a neural disease in part. [31]


Physical Examination

Physical findings relate to albinism, which affects the skin and the eyes. Pulmonary fibrosis can also be evaluated on physical examination.

Skin findings in Hermansky-Pudlak syndrome

Patients with Hermansky-Pudlak syndrome commonly have blond hair and pale skin, as demonstrated in the image below. Some have brown hair and brown eyes.

The face of a Puerto Rican girl with Hermansky-Pud The face of a Puerto Rican girl with Hermansky-Pudlak syndrome. Note the blond hair and the pale skin.

Melanocytic nevi with dysplastic features, acanthosis nigricans–like lesions in the axillae and the neck, and trichomegaly have been reported to occur.

Metastatic skin involvement of granulomatous colitis in Hermansky-Pudlak syndrome has been reported. [32]

Ocular findings in Hermansky-Pudlak syndrome

Ocular findings in Hermansky-Pudlak syndrome include poor visual acuity, refractive errors associated with with-the-rule astigmatism, strabismus, congenital nystagmus, prominent Schwalbe line, iris transillumination, foveal hypoplasia, and albinotic retinal mid periphery, as shown in the image below. [33]

Photo showing light brown eyes and a red reflectio Photo showing light brown eyes and a red reflection in the eyes.

Best-corrected visual acuity in patients with Hermansky-Pudlak syndrome ranges from 20/60 to 20/400 in the Snellen chart. Refractive errors range from high myopia to hyperopia.

Patients with Hermansky-Pudlak syndrome have congenital nystagmus. The most common types of strabismus found in patients with this syndrome are esotropia and exotropia. Vertical deviations have been reported.

Patients with Hermansky-Pudlak syndrome have various anterior segment abnormalities that include the following: a prominent Schwalbe line, iris transillumination, and presenile cataracts. Iris transillumination varies from almost total transillumination (pigment found at the collarette) to minimal peripheral transillumination.

Patients with Hermansky-Pudlak syndrome have foveal hypoplasia. Vascular architecture varies. Macular transparency (grading visibility of choroidal vessels) ranges from transparent to opaque. These patients have albinotic mid periphery.

Patients with Hermansky-Pudlak syndrome can have poor binocular vision and have no color-vision defects on Ishihara testing. Patients with Hermansky-Pudlak syndrome have pale optic nerves, and visual-evoked potentials show excessive decussation of the optic nerve fibers. Additionally, iris heterochromia with Hermansky-Pudlak syndrome has been reported. [34]

Pulmonary and cardiac findings in Hermansky-Pudlak syndrome

Auscultation of patients' lungs is important since patients may have impaired lung function. Patients with Hermansky-Pudlak syndrome have a risk of developing pulmonary fibrosis and susceptibility is linked to the alveolar epithelium. [35] A case of pulmonary alveolar proteinosis has been reported. [36]

Accumulation of ceroid in the heart can cause cardiomyopathy in these patients; thus, auscultation of the heart is important.



The most common complication is bleeding, and care should be taken to minimize its effects in surgery and to avoid trauma. Ceroid can infiltrate all body organs and can lead to pulmonary failure, kidney failure, cardiomyopathy, colitis, and other organ malfunctions. In particular, pulmonary complications can occur following general endotracheal anesthesia. Patients with Hermansky-Pudlak syndrome are photosensitive, which increases the risk for the development of skin cancers as well as worsening visual function.