JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Volume 88 May 1995

Oculocutaneous albinismand bruising in two sisters-probable Hermansky-Pudlaksyndrome

Julia P Ellis FRCP DCH Atherton Gray MD MRCPathFrances Richards FRCS FRCOphth

J R Soc Med 1995;88:293P-294P

CASE PRESENTED TO SECTION OF DERMATOLOGY, 18 NOVEMBER 1993

Keywords: oculocutaneous albinism; Hermansky-Pudlak syndrome

Cases of Hermansky-Pudlak syndrome may present tothe dermatologist, ophthalmologist or haematologist.Classically the diagnosis rests on the triad ofoculocutaneous albinism, a bruising tendency and thepresence of characteristic pigmented-containing cells inthe bone marrowl. Specific tests of platelet functioncan, however, suggest the diagnosis without recourse toinvasive techniques. We describe the disease in twoyoung sisters.

CASE REPORT

Both sisters (EG born 3.10.88 and CG born 3.9.91) werenoted to have 'funny' eyes at birth and were later found tohave nystagmus and fair skin. A diagnosis of tyrosinase-positive oculocutaneous albinism was made. Both startedbruising easily when they began to walk and EG had severalminor nose bleeds. The parents were non-consanguinouswith normal skin pigmentation, visual function and nohistory of bruising.

The physical findings in both children were the same,namely horizontal nystagmus, blue irides and albinoid fundi.The fundi were pale with prominent choroidal vessels due tothe lack of pigment in the choroid and retinal pigmentepithelium. EG was significantly myopic and CG had mildhypermetropia. Their skin was fair and they had fair but notwhite hair. EG became sunburnt after minimal sun exposure.

EG had a normal full blood count, blood film andclotting screen. The template bleeding time slightlyprolonged (10.5 min). Platelet function tests (Figure 2)showed primary aggregation with adenosine diphosphate(ADP) with no secondary aggregation when compared tonormal controls (Figure 1). Platelet ADP and adenosinetriphosphate (ATP) were assayed in both children and

Time (min)Figure 1 Platelet aggregation. Patient EG

201

'01

601

801

1001

1 2 3 4Time (min)

Figure 2 Platelet aggregation. Normal control

5

parents (Table 1). The platelet ADP content was reduced inEG and CG had an increased ATP/ADP ratio.

Advice was given on the avoidance of sun exposure andthe use of high protection sun screens to reduce the risk ofsunburn and cutaneous neoplasia. Appropriate correctiveand tinted lenses were prescribed. Aspirin, non-steroidalanti-inflammatories and intramuscular injections werecontraindicated and limitations were advised on activitieswhich carried a risk of trauma. Platelet transfusions werereserved for the treatment of major bleeding and asprophylaxis for surgery. Infusions ofDDAVP (desmopressin)and cryoprecipitate2 have also been reported to reduce thebleeding tendency.

DISCUSSION

Two siblings with tyrosinase-positive oculocutaneousalbinism were investigated for a bruising tendency.Abnormal platelet function in the older child wasdemonstrated by a slightly prolonged bleeding time andfailure of secondary platelet aggregation. A storage pooldefect of platelets was demonstrated in both children by thereduced ADP content of the platelets (Table 1) and adiagnosis of Hermansky-Pudlak syndrome (HPS) was made.

20S

601

80X

1001

Pnncess Margaret HospiW, Okus Road, Swindon, SN1 4JU, Wilts. UKCorrespondence to: Dr Julia Ellis 293P

JOURNAL OF THE ROYAL SOCIETY OF MEDICINE Volume 88 May 1995

Table 1 Platelet nuclootides Platelet concentrations of adenosinetriphosphate (ATP) and adenosine diphosphate (ADP).

Normal range(nmIlO8

EG CG Mother Father platelets)

Total 6.6 5.9 7.4 7.2 5-12

ATP 4.3 4.1 4.8 4.9 3.5-8

ADP 2.3 1.8 2.7 2.4 2.5-6

ATP/ADP ratio 1.9 2.3 1.8 2.1 1.0-2.2

The platelet defect in HPS is associated with reducedstorage of adenine nucleotides3 which are important in theplatelet release reaction. An identical platelet defect has beendescribed which is not associated with albinism4 but thepattern of inheritance appears to be autosomal dominant inthose cases not recessive as in HPS and the present cases.Only a minority of albino patients have a platelet defect orsuffer from a bleeding tendency5 and not all have abnormalpigment-containing cells in the marrow. Nevertheless thecombination of albinism, probable recessive inheritance andstorage pool defect of platelets in these children made thediagnosis of HPS sufficiently likely that the need for bonemarrow biopsy was avoided.

The cause of HPS is likely to be a single gene mutation5 buta common molecular abnormality has not been identified.

There is some evidence that the platelet defect may be aquantitative or qualitative abnormality of a dense bodymembrane protein leading to impaired storage ofnucleotides6. It may be that an analogous protein deficiencyin the melanosome membrane could account for the tyrosinase-positive albino phenotype where melanogenesis itself is normal.

Awareness of the diagnosis is important in the preventionof skin disease, in the optimization of visual function and inthe haematological management of surgery and trauma.

REFERENCES

1 Hermansky F, Pudlak P. Albinism associated with hemmorrhagicdiathesis and unusual pigmented reticular cells in the bone marrow:report of two cases with histochemical studies. Blood 1959;14:162-9

2 Wijermans PW. Hermansky Pudlak syndrome: correction of bleedingtime by l-desamino-8D-arginine vasopressin. AmjHematol 198;30: 154-7

3 White JG, Edson JR, Desnick SJ, Witkop CJ. Studies of platelets in avariant of the Hermansky-Pudlack syndrome. AmJ Pathol 1971;63:319

4 Weiss HJ, Chevernick PA, Zalusky R, Factor A. A familial defect inplatelet function associated with impaired release of adenine diphosphate.N Englj Med 1969;281:1264

5 Hardisty RM, Mills DCB, Ketsa-ard K. The platelet defect associatedwith albinism. BrJ Haem 1972;23:679-92

6 Gerrard JM, Lint D, Sims PJ, et a). Identification of a platelet densegranule membrane protein that is deficient in a patient with theHermansky Pudlak syndrome. Blood 1991;77:101-12

(Accepted I August 1994)

Cold urticaria, raised IgEand HIV infection

R C Yu MD MRCP1 B Evans FRCP2 J J Cream FRCP1

J R Soc Med 1 995;88:294P-295P

CASE PRESENTED TO SECTION OF DERMATOLOGY, 16 MAY 1994

Keywords: cold urticaria; IgE; human immunodeficiency virus; acquiredimmunodjiciency syndrome

We present a patient with cold urticaria as an unusualand late cutaneous manifestation of acquiredimmunodeficiency syndrome. The severe CD4 celldepletion and markedly elevated serum IgE levels in ourpatient provide some insights into certain aspects ofimmune regulatory mechanisms.

CASE REPORT

A 38-year old woman contracted human immunodeficiencyvirus (HIV) infection through intravenous drug abuse inSpain between 1977 and 1985. Her circulating CD4 counthad fallen below 10/mm3 by 1992. Despite treatment withazidothymidine (AZT) and dapsone she developed culture-positive Pneumocystis carinii pneumonia in June 1992. Afterrecovering from her pneumonia, she continued to feelunwell for many months with recurrent fever, severegastrointestinal symptoms and uro-genital ulcerations. Shereceived a variety of medications including antibiotics,antifungals, acyclovir and didanosine (DDI). In August1993, she developed itchy papules on her face and flank,and noticed abnormal skin reaction to the cold. Severaldrugs were stopped with no improvement. In January1994, she was referred to the dermatology departmentwith cold-contact urticaria which could be triggered by acool breeze, and cold water immersion. Iced drinks or icecream caused swelling in her throat. Clinical examinationrevealed erythematous urticated papules along her jawlineand over the loins. Application of an ice cube to herforearm for 30 s resulted in an immediate marked flare andwheal reaction.

Departments of 1 Dermatology and 2GenHtourinary Medicine, Charing Cross andWestminster Medical School, Du Cane Road, London W12 ONN, UK

Correspondence to: Dr Raymond Yu, Unit of Dermatology, Royal PostgraduateMedical School294P