Complementary Use of U.S. FDA's Adverse Event Reporting System and Sentinel System to Characterize Direct Oral Anticoagulants-Associated Cutaneous Small Vessel Vasculitis.

BACKGROUND: Cutaneous small vessel vasculitis (CSVV) has been reported after exposure to direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, and edoxaban. OBJECTIVE: We used the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to describe clinical characteristics associated with CSVV among DOAC-exposed patients. Furthermore, we characterized this signal in the Sentinel System to relate the clinical data from the individual FAERS cases to population-based electronic healthcare data. METHODS: We queried FAERS for all cases of CSVV associated with DOACs from U.S. approval date of each DOAC through March 16, 2018. Within the Sentinel System, we identified incident CSVV cases using ICD-9 and ICD-10 diagnosis codes among adults aged ≥ 30 years who received a DOAC in the prior 90 days between January 1, 2010, and June 30, 2018. We excluded patients with evidence of select autoimmune diagnoses in the 183 days prior to their CSVV diagnoses and reported patient characteristics in the 183-day period prior to CSVV diagnoses. RESULTS: In FAERS, we identified 50 cases of CSVV reported with rivaroxaban (n=26), apixaban (n=14), dabigatran (n=9), and edoxaban (n=1). Approximately 50% of the cases reported time to onset within 10 days after DOAC exposure. When specified, the predominant type of CSVV reported was leukocytoclastic vasculitis (n=31), followed by Henoch-Schonlein purpura (n=4). Hospitalization occurred in most of the cases (n=37). Switching of the offending agent after the development of CSVV was reported (n=26). Three rivaroxaban (n=3) cases and one dabigatran case (n=1) reported positive rechallenge. In the Sentinel system, we identified 3659 CSVV cases with prior DOAC exposure, with 85% of events occurring within 10 days. CONCLUSIONS: The assessment of FAERS cases, combined with the temporal clustering of the Sentinel System cases suggest a possible causal relationship of DOACs and CSVV. Future efforts should characterize the risk of CSVV among the various DOAC users.

Pruritus after discontinuation of cetirizine.

BACKGROUND: Intense pruritus or itching emerging after discontinuation of cetirizine has been the subject of postmarketing reports submitted to the U.S. Food and Drug Administration (FDA), published in the medical literature, and discussed on the internet. To better understand and further investigate this adverse event, we analyzed cases of pruritus occurring after discontinuation of cetirizine in the FDA Adverse Event Reporting System (FAERS) database and medical literature. METHODS: We conducted a retrospective study to identify and describe cases of pruritus occurring after discontinuation of cetirizine in the FAERS database and medical literature through April 24, 2017. Data collected from the reports included demographic information, reason for use, serious outcome, report source, duration of cetirizine use, time to onset of pruritus after cetirizine discontinuation, presence of associated urticaria, treatment for pruritus, concomitant comorbidities and medications associated with pruritus, rechallenge information, and patient outcome information. RESULTS: We identified 146 cases of pruritus after discontinuation of cetirizine. Reporting frequency increased starting in 2008. The median patient age was 38 years (n = 141), ranging from 6 to 71 years, and cases were predominantly reported in females (n = 110). Most cases (n = 115) were submitted directly to the FDA from consumers or healthcare providers. The median duration of use of cetirizine prior to discontinuation was 24 months (n = 130), ranging from 0.3 to 172.2 months. The median time to onset of pruritus from discontinuation was 2 days (n = 91), ranging from 0.5 to 5 days. Of the 55 cases that reported discontinuation of cetirizine again after restarting, 54 reported pruritus recurrence. CONCLUSIONS: Our case series provided evidence of an association between the discontinuation of cetirizine and the development of pruritus. The mechanism by which cetirizine causes pruritus upon discontinuation is unknown. Patients and prescribers should have knowledge of this adverse event, given the widespread use and availability of cetirizine, and potential impact on patient quality of life.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Standard Reporting and Evaluation Guidelines: Results of a National Institutes of Health Working Group.

Importance: Toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS) are rare, acute, life-threatening dermatologic disorders involving the skin and mucous membranes. Research into these conditions is hampered by a lack of standardization of case reporting and data collection. Objective: To establish a standardized case report form to facilitate comparisons and maintain data quality based on an international panel of SJS/TEN experts who performed a Delphi consensus-building exercise. Evidence Review: The elements presented for committee scrutiny were adapted from previous case report forms and from PubMed literature searches of highly cited manuscripts pertaining to SJS/TEN. The expert opinions and experience of the members of the consensus group were included in the discussion. Findings: Overall, 21 out of 29 experts who were invited to participate in the online Delphi exercise agreed to participate. Surveys at each stage were administered via an online survery software tool. For the first 2 Delphi rounds, results were analyzed using the Interpercentile Range Adjusted for Symmetry method and statements that passed consensus formulated a new case report form. For the third Delphi round, the case report form was presented to the committee, who agreed that it was "appropriate and useful" for documenting cases of SJS/TEN, making it more reliable and valuable for future research endeavors. Conclusions and Relevance: With the consensus of international experts, a case report form for SJS/TEN has been created to help standardize the collection of patient information in future studies and the documentation of individual cases.

Chemical Leukoderma Associated with Methylphenidate Transdermal System: Data From the US Food and Drug Administration Adverse Event Reporting System.

OBJECTIVE: To identify and characterize cases of chemical leukoderma, an underrecognized adverse event, associated with the methylphenidate transdermal system (MTS) reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS). STUDY DESIGN: We searched the Food and Drug Administration Adverse Event Reporting System for reports of chemical leukoderma associated with MTS, received by the Food and Drug Administration from April 6, 2006 to December 23, 2014. RESULTS: We identified 51 cases of chemical leukoderma reported with the use of MTS. The median age was 11 years; 43 cases reported leukoderma at or near the application site only, and 7 reported leukoderma at other parts of the body in addition to the application site; 1 case did not provide enough information to confirm the affected site. The time to onset ranged from 2 months to 4 years after the initiation of MTS. MTS was discontinued in 31 cases. Thirteen patients were prescribed treatment for repigmentation. Three cases reported continued spread of leukoderma after MTS was discontinued. Nineteen cases were diagnosed as vitiligo, including 5 cases reporting histologic features consistent with vitiligo. Leukoderma was persistent in all cases. The median follow-up interval after the discontinuation of MTS in 23 cases was 14 months. CONCLUSIONS: As outlined in recent changes to the prescribing information for MTS, health care professionals need to be aware of the potential risk of chemical leukoderma caused by MTS, especially given that chemical leukoderma is often misdiagnosed as idiopathic vitiligo. MTS should be discontinued at the earliest sign of pigment loss and other treatment options considered.

Identification of Stevens-Johnson syndrome and toxic epidermal necrolysis in electronic health record databases.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) carry a high mortality risk. While identifying clinical and genetic risk factors for these conditions has been hindered by their rarity, large electronic health databases hold promise for identifying large numbers of cases for study, especially with the introduction in 2008 of ICD-9 codes more specific for these conditions. OBJECTIVE: The objective of this study is to estimate the validity of ICD-9 codes for ascertaining SJS/TEN in 12 collaborating research units in the USA, covering almost 60 million lives. METHODS: From the electronic databases at each site, we ascertained potential cases of SJS/TEN using ICD-9 codes. At five sites, a subset of medical records was abstracted and standardized criteria applied by board-certified dermatologists to adjudicate diagnoses. Multivariate logistic regression was used to identify factors independently associated with validated SJS/TEN cases. RESULTS: A total of 56 591 potential cases of SJS/TEN were identified. A subset of 276 charts was selected for adjudication and 39 (of the 276) were confirmed as SJS/TEN. Patients with the ICD-9 codes introduced after 2008 were more likely to be confirmed as cases (OR 3.32; 95%CI 0.82, 13.47) than those identified in earlier years. Likelihood of case status increased with length of hospitalization. Applying the probability of case status to the 56 591 potential cases, we estimated 475-875 to be valid SJS/TEN cases. CONCLUSION: Newer ICD-9 codes, along with length of hospitalization, identified patients with a high likelihood of SJS/TEN. This is important for identification of subjects for future pharmacogenomics studies.

Allopurinol pharmacogenetics: assessment of potential clinical usefulness.

Use of pharmacogenetics to inform treatment decisions remains a priority for clinicians, patients and public health agencies. We previously developed a framework for systematically assessing whether pharmacogenetic test information would likely bring value to clinical decision-making and enjoy practical uptake. We applied this tool to allopurinol to determine potential usefulness of HLA genetic information in assessing risk for allopurinol-induced severe cutaneous adverse reactions. We quantified allopurinol use data and the magnitude of adverse event signals using US FDA databases, reviewed reported cases of allopurinol-associated severe cutaneous adverse reactions to assess whether clinical subtypes of patients could be identified, performed pooled analyses of associations between HLA variation and allopurinol-induced severe cutaneous adverse reactions and described considerations in clinical implementation of allopurinol pharmacogenetics.

Tumor necrosis factor alpha blockers and malignancy in children: forty-eight cases reported to the Food and Drug Administration.

OBJECTIVE: Malignancies reported in children using tumor necrosis factor alpha (TNFalpha) blockers have raised concerns of a potential increased risk. This study was undertaken to investigate postmarketing reports of malignancy in children treated with TNF blockers. METHODS: The FDA's Adverse Event Reporting System was searched to identify malignancies associated with the use of infliximab, etanercept, and adalimumab in children in whom therapy was initiated between the ages of 0 and 18 years. The reporting rates for infliximab and etanercept were compared with the background rate of malignancy in the general pediatric population. RESULTS: Forty-eight reports of malignancy in children were identified: 31 following infliximab use, 15 following etanercept use, and 2 following adalimumab use. Half of the malignancies reported were lymphomas and included both Hodgkin's and non-Hodgkin's lymphoma. The remaining reported cases involved a variety of different malignancies including leukemia, melanoma, and solid organ cancers. The majority of the reported cases (88%) involved the concomitant use of other immunosuppressants. Reporting rates for malignancy showed that infliximab had a consistently higher reporting rate when compared with background rates in the general pediatric population for lymphomas and all malignancies. The reporting rates for etanercept were elevated above background for lymphomas and were on par with background for all malignancies. CONCLUSION: There is evidence that treatment with TNF blockers in children may increase the risk of malignancy. However, the cases were confounded by the potential risk of malignancy associated with underlying illnesses and the use of concomitant immunosuppressants; therefore, a clear causal relationship could not be established.

Risk factors for statin-associated rhabdomyolysis.

PURPOSE: To identify and characterize risk factors for rhabdomyolysis in patients prescribed statin monotherapy or statin plus fibrate therapy. METHODS: A nested case-control study was conducted within a cohort of 252,460 new users of lipid-lowering medications across 11 geographically dispersed U.S. health plans. Twenty-one cases of rhabdomyolysis confirmed by medical record review were compared to 200 individually matched controls without rhabdomyolysis. A conditional logistic regression model was applied to evaluate the effects of age, gender, comorbidities, concurrent medication use, dosage, and duration of statin use on the development of rhabdomyolysis. RESULTS: Statin users 65 years of age and older have four times the risk of hospitalization for rhabdomyolysis than those under age 65 (odds ratio (OR) = 4.36, 95% confidence interval (CI): 1.5,14.1). We also observed a joint effect of high statin dosage and renal disease (p = 0.022). When these two variables were added to the model with age, we obtained an OR of 5.73 for dosage (95%CI: 0.63, 52.6) and 6.26 for renal disease (95%CI: 0.46, 63.38). Although not statistically significant, we did observe a greater than twofold increase in risk for rhabdomyolysis among females (OR = 2.53, 95%CI: 0.91, 7.32). CONCLUSIONS: Findings of this study indicate that older age is a risk factor for rhabdomyolysis among statin users. Although the evidence is not as strong, high statin dosage, renal disease, and female gender may be additional risk factors. Patients at higher risk of developing rhabdomyolysis should be closely monitored for signs and symptoms of the disease.

Comparison of reporting of Stevens-Johnson syndrome and toxic epidermal necrolysis in association with selective COX-2 inhibitors.

BACKGROUND: Stevens-Johnson syndrome and toxic epidermal necrolysis are closely related severe acute life-threatening, drug-induced skin disorders. The US FDA Adverse Events Reporting System (AERS) has received reports of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with the use of the recently introduced selective cyclo-oxygenase (COX)-2 inhibitor NSAIDs, two of which are also sulfonamides. OBJECTIVE: The objective of this study is to review cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the FDA associated with the use of the selective COX-2 inhibitor NSAIDs celecoxib, rofecoxib and valdecoxib, and to compare reporting rates of the two conditions associated with these drugs to each other, meloxicam (an oxicam NSAID that came on the US market at a similar time) and the background incidence rate. METHODS: We reviewed all US cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the FDA AERS database associated with the use of celecoxib, rofecoxib, valdecoxib and meloxicam since these agents were first marketed. We utilised AERS and drug use data to calculate reporting rates for each drug after the first 2 years of marketing. We obtained the background rate from the medical literature. RESULTS: Up to the end of March 2004, there were 63 cases of Stevens-Johnson syndrome/toxic epidermal necrolysis reported with valdecoxib use, 43 with celecoxib, 17 with rofecoxib (the non-sulfonamide coxib) and none for meloxicam. In the first 2 years of marketing the reporting rate for Stevens-Johnson syndrome/toxic epidermal necrolysis with valdecoxib was 49 cases per million person-years of use, 6 cases per million person-years for celecoxib and 3 cases per million person-years for rofecoxib. The reporting rates for the sulfonamide coxibs were substantially higher than the background rate of 1.9 cases per million population per year, with the valdecoxib rate being 8-9 times that of celecoxib and approximately 25 times that of the background rate. CONCLUSION: There is a strong association between Stevens-Johnson syndrome/toxic epidermal necrolysis and the use of the sulfonamide COX-2 inhibitors, particularly valdecoxib. Physicians should be aware of the possibility of this serious life-threatening event when prescribing these drugs and advise patients to discontinue use at the earliest possible sign or symptom.

Health plan administrative databases can efficiently identify serious myopathy and rhabdomyolysis.

OBJECTIVE: We evaluated the positive predictive values (PPVs) of specific criteria based upon International Classification of Diseases, 9th revision (ICD-9-CM) codes documented in health plan administrative databases for identification of cases of serious myopathy and rhabdomyolysis. STUDY DESIGN AND SETTING: We conducted a retrospective study among patients enrolled in 11 geographically dispersed managed care organizations. Cohorts of new users of specific statins and fibrates were identified by selecting patients with an initial dispensing of the drug during the period 1 January 1998 to 30 June 2001. Potential cases of serious myopathy or rhabdomyolysis were identified using specific criteria based upon ICD-9-CM codes suggesting a muscle disorder or acute renal failure. RESULTS: A total of 194 hospitalizations meeting the criteria for chart review selection were identified among 206,732 new users of statins and 15,485 new users of fibrates. Overall, 31 cases of serious, clinically important myopathy or rhabdomyolysis (18%) were confirmed through chart review. Of these, 26 (84%) had a claim including codes for myoglobinuria (ICD-9-CM 791.3) or other disorders of muscle, ligament, and fascia (ICD-9-CM 728.89). A PPV of 74% (26 of 35 patients meeting criteria) was found for a composite definition that included (1) a primary or secondary discharge code for myoglobinuria, (2) a primary code for "other disorders of muscle," or (3) a secondary code for "other disorders of muscle" accompanied by a claim for a CK test within 7 days of hospitalization or a discharge code for acute renal failure. CONCLUSION: For rare adverse events such as serious myopathy or rhabdomyolysis, large population-based databases that include diagnosis and laboratory test claims data can facilitate epidemiologic research.

Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs.

CONTEXT: Lipid-lowering agents are widely prescribed in the United States. Reliable estimates of rhabdomyolysis risk with various lipid-lowering agents are not available. OBJECTIVE: To estimate the incidence of rhabdomyolysis in patients treated with different statins and fibrates, alone and in combination, in the ambulatory setting. DESIGN, SETTING, AND PATIENTS: Drug-specific inception cohorts of statin and fibrate users were established using claims data from 11 managed care health plans across the United States. Patients with at least 180 days of prior health plan enrollment were entered into the cohorts between January 1, 1998, and June 30, 2001. Person-time was classified as monotherapy or combined statin-fibrate therapy. MAIN OUTCOME MEASURE: Incidence rates of rhabdomyolysis per 10,000 person-years of treatment, number needed to treat, and relative risk of rhabdomyolysis. RESULTS: In 252,460 patients treated with lipid-lowering agents, 24 cases of hospitalized rhabdomyolysis occurred during treatment. Average incidence per 10,000 person-years for monotherapy with atorvastatin, pravastatin, or simvastatin was 0.44 (95% confidence interval [CI], 0.20-0.84); for cerivastatin, 5.34 (95% CI, 1.46-13.68); and for fibrate, 2.82 (95% CI, 0.58-8.24). By comparison, the incidence during unexposed person-time was 0 (95% CI, 0-0.48; P = .056). The incidence increased to 5.98 (95% CI, 0.72-216.0) for combined therapy of atorvastatin, pravastatin, or simvastatin with a fibrate, and to 1035 (95% CI, 389-2117) for combined cerivastatin-fibrate use. Per year of therapy, the number needed to treat to observe 1 case of rhabdomyolysis was 22,727 for statin monotherapy, 484 for older patients with diabetes mellitus who were treated with both a statin and fibrate, and ranged from 9.7 to 12.7 for patients who were treated with cerivastatin plus fibrate. CONCLUSIONS: Rhabdomyolysis risk was similar and low for monotherapy with atorvastatin, pravastatin, and simvastatin; combined statin-fibrate use increased risk, especially in older patients with diabetes mellitus. Cerivastatin combined with fibrate conferred a risk of approximately 1 in 10 treated patients per year.

Allergic contact dermatitis from topical doxepin: Food and Drug Administration's postmarketing surveillance experience.

A total of 26 postmarketing cases of allergic contact dermatitis to doxepin 5% cream were reported to the Food and Drug Administration. Our findings suggest that allergic contact dermatitis was more common when treatment duration exceeded the recommended 8 days. Allergic contact dermatitis to doxepin cream should be considered in patients whose condition fails to improve or worsens with doxepin use.

Clinical, pathologic, and immunologic features of human T-lymphotropic virus type I- associated infective dermatitis in children

Objectives: To define the clinical and laboratory features associated with infective dermatitis (ID) and confirm its association with human T-lymphotropic virus type 1 (HTLV-I). Design: A case series of patients with ID were compared with patients with atopic dermatitis (AD) which is an important disease in the differential diagnosis of ID. Setting: Patients were recruited from dermatology and pediatric clinics at the University Hospital of the West Indies and the Bustamante Children's Hospital, Kingston, Jamaica. Main Outcome Measures: Clinical and laboratory features of patients with AD were compared with those of patients with ID. Patients: Consecutive patients older than 1« years diagnosed as having ID (n=50) and AD (n=35) were enrolled based on clinical findings. Results: The mean age of patients with ID and AD were 6.9 and 7.8 years, respectively. Histologically, both disease were predominantly chronic dermatitis... Conclusion: Infective dermatitis is a distinct clinical entity associated with HTLV-I, which plays a role in the pathogenesis and immune perturbations observed.(AU)

The prevalence of atopic dermatitis in black Caribbean children in London and Kingston, Jamaica

It has been suggested that black children of West Indian origin living in London have a higher prevalence of atopic dermatitis (AD) than their counterparts living in the Caribbean. (Williams HC et. al London-born black Caribbean children are at increased risk of atopic dermatitis. J Am Acad Dermatol 1995; 32: 212-7). To test this hypothesis, we undertook a colloborative study on the prevalence of atopic dermatitis in school children in Lambeth, London and Kingston, Jamaica. Questionnaires were sent to 2126 and 3957 parents of children aged 4 to 11 years attending seven primary schools in London and six schools in Kingston respectively. The questionnaires requested screening information on symptoms of AD and parentally nominated ethnic group of the child. Children whose parents responded affirmatively to the presence of an itchy rash or the presence of generally dry skin (N=562) were examined during two visits to the schools in London. In Kingston, all children whose parents responded and gave consent were examined (N=3027) by the same dermatologist. Cases of AD were defined using the UK Working Party's Diagnostic Criteria. The overall response rate in London and Kingston was 70.3 percent and 86.2 percent respectively. The overall prevalence of AD was 10.8 percent (162/1495) and 4.9 percent (166/3409) in London and Kingston respectively. The prevalence of AD in black children living in London was 18.9 percent (60/317) compared with 4.6 percent (94/2029). These results suggest that black Caribbean children in London are at an increased risk (odds ratio 4.81, 95 percent confidence interval 3.3 to 6.9, p<0.001) of developing atopic dermatitis when compared to their counterparts living in Jamaica. Possible reasons for these large prevalence differences are currently being investigated. (AU)

HTLV-I seroprevalence among patients with severe skin disorders at the University Hospital of the West Indies, Jamaica - abstract

This prospective study of seroprevalence of human T-lymphotropic virus Type I (HTLV_I) among patients with sever skin disorders at the University Hospital of the West Indies (UHWI) was undertaken because of the high prevalence of skin lesions in patients with adult T-cell lymphoma/leukaemia (ATL) both before and after diagnosis was made. Of 901 patients admitted to the dermatology ward between May 1989 and October 1996, 195 were found to be HTLV-I seropositive, giving a seroprevalence rate of 21.6 percent. The commonest disorders among the HTLV-I positive group were infected dermatitis (ID), ATL, crusted scabies and eczema other than ID. Skin disorders with the highest HTLV-I positive rates were ID (100 percent), ATL (85.7 percent) and crusted scabies (70 percent). Eczema other than ID, erythroderma and psoriasis also had a significantly higher HTLV-I positivity rate than the general Jamaican population but less than the first three mentioned. Seven patients were co-infected with HTLV-I and HIV-I, and the commonest skin disorder among this group was seborrhoeic dermatitis. There was 100 percent positivity among fifteen mothers of ID patients tested. The results confirm the hypothesis that there is a higher HTLV-I seroprevalence rate among patients with severe skin disorders than the general population in Jamaica. (AU)

Childhood dermatitis in the tropics: with special emphasis on infective dermatitis, a marker for infection with human T-cell leukemia virus-I

Eczema in the tropics is a common problem. Although it is a major cause of discomfort among children worldwide, a warm tropical climate often has important repercussions for children with dermatitis. The original description by Sweet empahasized that interest in tropical eczemas extended to the English, as children of West Indian immigrants in England were affected. Likewise, immigrants may carry these disorders with them to the United States. In Jamaica, a tropical country, the largest and most populous of the English-speaking Caribbena islands, eczema is by far the most common skin disorder seen in children attending dermatology clinics. Reports from other Caribbean islands suggest that this is true for the region as a whole. In 1981, Alabi and La Grenade reported that from 1971 to 1975 eczema accounted for 46.7 percent of skin rashes seen in children at the University Hospital of the West Indies. Review of the period 1988 to 1993 showed that 52 percent of the 601 children who attended the skin clinic for the first time had eczema, confirming the earlier finding. In this latter review, atopic eczema was the most common type of eczema (52 percent), followed by seborrheic eczema (20 percent) and infective dermatitis (10 percent). The remaining 18 percent had a variety of unclassified eczemas including pityriasis alba, discoid eczema, acute vesicular eczema of the hands and/or feet, and hyperkeratotic eczema of the feet.(AU)

HLA DRBI *DQB1* haplotype in HTLV-I-associated familial infective dermatitis may predict development of HTLV-I-associated myelopathy/tropical spastic paraparesis

A possible causal association between infective dematitis and HTLV-I infection was reported familial infective dematitis (ID) occurring in a 26-year-old mother and her 9-year-old son. The mother was first diagnosed with ID in 1969 at the age of 2 years in the Dermatology Unit at the University Hospital of the West indies (U.H.W.I.) in Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years, also at U.H.W.I. Both mother and son are HTLV-I-seropositive. A second, younger son, currently age 2 years, is also HTLV-I-seropositive, but without clinical evidence of ID. Major hitocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB*DQBI* (1101-0301), in the mother and her 2 sons. This same haplotype has been described among Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and has been associated with a possible pathologically heightened immune repsonse to HTLV-I infection. The presence of this haplotype in these familial ID cases with clinical signs of HAM/TSP may have contributed to their risk for development of HAM/TSP. The unaffected, HTLV-I seropositive younger son requires close clinical follow-up. (AU)