Alexandria Riopelle, MD

Autoimmune bullous dermatoses (ABDs) develop due to antibodies directed against antigens within the epidermis or at the dermoepidermal junction. They are categorized histologically by the location of acantholysis (separation of keratinocytes), clinical presentation, and presence of autoantibodies. The most common ABDs include pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid (BP). These conditions present on a spectrum of symptoms and severity.¹

Although multiple studies have evaluated the impact of bullous dermatoses on mental health, most were designed with a small sample size, thus limiting the generalizability of each study. Sebaratnam et al² summarized several studies in 2012. In this review, we will analyze additional relevant literature and systematically combine the data to determine the psychological burden of disease of ABDs. We also will discuss the existing questionnaires frequently used in the dermatology setting to assess adverse psychosocial symptoms.

Methods

We searched PubMed, MEDLINE, and Google Scholar for articles published within the last 15 years using the terms bullous pemphigoid, pemphigus, quality of life, anxiety, and depression. We reviewed the citations in each article to further our search.

Criteria for Inclusion and Exclusion—Studies that utilized validated questionnaires to evaluate the effects of pemphigus vulgaris, pemphigus foliaceus, and/or BP on mental health were included. All research participants were 18 years and older. For the questionnaires administered, each study must have included numerical scores in the results. The studies all reported statistically significant results (P<.05), but no studies were excluded on the basis of statistical significance.

Studies were excluded if they did not use a validated questionnaire to examine quality of life (QOL) or psychological status. We also excluded database, retrospective, qualitative, and observational studies. We did not include studies with a sample size less than 20. Studies that administered questionnaires that were uncommon in this realm of research such as the Attitude to Appearance Scale or The Anxiety Questionnaire also were excluded. We did not exclude articles based on their primary language.

Results

A total of 13 studies met the inclusion criteria with a total of 1716 participants enrolled in the trials. The questionnaires most commonly used are summarized in Table 1. Tables 2 and 3 demonstrate the studies that evaluate QOL and psychological state in patients with bullous dermatoses, respectively.

The Dermatology Life Quality Index (DLQI) was the most utilized method for analyzing QOL followed by the Skindex-17, Skindex-29, and 36-Item Short Form Health Survey. The DLQI is a skin-specific measurement tool with higher scores translating to greater impairment in QOL. Healthy patients have an average score of 0.5.³ The mean DLQI scores for ABD patients as seen in Table 2 were 9.45, 10.18, 16, 10.9, and 10.1.^13-15,18,22 The most commonly reported concerns among patients included feelings about appearance and disturbances in daily activities.¹⁸ Symptoms of mucosal involvement, itching, and burning also were indicators of lower QOL.^15,18,20,22 Furthermore, women consistently had lower scores than men.^15,17,19,25 Multiple studies concluded that severity of the disease correlated with a lower QOL, though the subtype of pemphigus did not have an effect on QOL scores.^15,19,20,21 Lastly, recent onset of symptoms was associated with a worse QOL score.^15,18-20 Age, education level, and marital status did not have an effect on QOL.

To evaluate psychological state, the General Health Questionnaire (GHQ)-28 and -12 primarily were used, in addition to the Hospital Anxiety and Depression Scale; the International Classification of Diseases, Tenth Revision; the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; and the Beck Depression Inventory-II. As seen in Table 3, GHQ-12 positivity, reflecting probable minor nonpsychotic psychiatric disorders such as depression and anxiety, was identified in 47%, 39.7%, and 40% of patients with pemphigus^15,19,24; GHQ-28 positivity was seen in 77.5% of pemphigus patients.¹⁸ In the average population, GHQ positivity was found in up to 12% of patients.^26,27 Similar to the QOL scores, no significant differences were seen based on subtype of pemphigus for symptoms of depression or anxiety.^20,23

Comment

Mental Health of Patients With ABDs—Immunobullous diseases are painful, potentially lifelong conditions that have no definitive cure. These conditions are characterized by bullae and erosions of the skin and mucosae that physically are disabling and often create a stigma for patients. Across multiple different validated psychosocial assessments, the 13 studies included in this review consistently reported that ABDs have a negative effect on mental well-being of patients that is more pronounced in women and worse at the onset of symptoms.^13-25

QOL Scores in Patients With ABDs—Quality of life is a broad term that encompasses a general sense of psychological and overall well-being. A score of approximately 10 on the DLQI most often was reported in patients with ABDs, which translates to a moderate impact on QOL. Incomparison, a large cohort study reported the mean (SD) DLQI scores for patients with atopic dermatitis and psoriasis as 7.31 (5.98) and 5.93 (5.66), respectively.²⁸ In another study, Penha et al¹⁴ found that patients with psoriasis have a mean DLQI score of 10. Reasons for the similarly low QOL scores in patients with ABDs include long hospitalization periods, disease chronicity, social anxiety, inability to control symptoms, difficulty with activities of daily living, and the belief that the disease is incurable.^17,19,23 Although there is a need for increased family and social support with performing necessary daily tasks, personal relationships often are negatively affected, resulting in social isolation, loneliness, and worsening of cutaneous symptoms.

Severity of cutaneous disease and recent onset of symptoms correlated with worse QOL scores. Tabolli et al²⁰ proposed the reason for this relates to not having had enough time to find the best treatment regimen. We believe there also may be an element of habituation involved, whereby patients become accustomed to the appearance of the lesions over time and therefore they become less distressing. Interestingly, Tabolli et al¹⁷ determined that patients in the quiescent phase of the disease—without any mucosal or cutaneous lesions—still maintained lower QOL scores than the average population, particularly on the psychosocial section of the 36-Item Short Form Health Survey, which may be due to a concern of disease relapse or from adverse effects of treatment. Providers should monitor patients for mental health complications not only in the disease infancy but throughout the disease course.

Future Directions—Cause and effect of the relationship between the psychosocial variables and ABD disease state has yet to be determined. Most studies included in this review were cross-sectional in design. Although many studies concluded that bullous dermatoses were the cause of impaired QOL, Ren and colleagues²⁹ proposed that medications used to treat neuropsychiatric disorders may trigger the autoimmune antigens of BP. Possible triggers for BP have been reported including hydrochlorothiazide, ciprofloxacin, and dipeptidyl peptidase-4 inhibitors.^27,30-32 A longitudinal study design would better evaluate the causal relationship.

The effects of the medications were included in 2 cases, one in which the steroid dose was not found to have a significant impact on rates of depression²³ and another in which patients treated with a higher dose of corticosteroids (>10 mg) had worse QOL scores.¹⁷ Sung et al¹⁵ suggested this may be because patients who took higher doses of steroids had worse symptoms and therefore also had a worse QOL. It also is possible that those patients taking higher doses had increased side effects.¹⁷ Further studies that evaluate treatment modalities and timing in relation to the disease onset would be helpful.

Study Limitations—There are potential barriers to combining these data. Multiple different questionnaires were used, and it was difficult to ascertain if all the participants were experiencing active disease. Additionally, questionnaires are not always the best proxy for what is happening in everyday life. Lastly, the sample size of each individual study was small, and the studies only included adults.

Conclusion

As demonstrated by the 13 studies in this review, patients with ABDs have lower QOL scores and higher numbers of psychological symptoms. Clinicians should be mindful of this at-risk population and create opportunities in clinic to discuss personal hardship associated with the disease process and recommend psychiatric intervention if indicated. Additionally, family members often are overburdened with the chronicity of ABDs, and they should not be forgotten. Using one of the aforementioned questionnaires is a practical way to screen patients for lower QOL scores. We agree with Paradisi and colleagues¹⁹ that although these questionnaires may be helpful, clinicians still need to determine if the use of a dermatologic QOL evaluation tool in clinical practice improves patient satisfaction.

Autoimmune bullous dermatoses (ABDs) develop due to antibodies directed against antigens within the epidermis or at the dermoepidermal junction. They are categorized histologically by the location of acantholysis (separation of keratinocytes), clinical presentation, and presence of autoantibodies. The most common ABDs include pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid (BP). These conditions present on a spectrum of symptoms and severity.¹

Although multiple studies have evaluated the impact of bullous dermatoses on mental health, most were designed with a small sample size, thus limiting the generalizability of each study. Sebaratnam et al² summarized several studies in 2012. In this review, we will analyze additional relevant literature and systematically combine the data to determine the psychological burden of disease of ABDs. We also will discuss the existing questionnaires frequently used in the dermatology setting to assess adverse psychosocial symptoms.

Methods

We searched PubMed, MEDLINE, and Google Scholar for articles published within the last 15 years using the terms bullous pemphigoid, pemphigus, quality of life, anxiety, and depression. We reviewed the citations in each article to further our search.

Criteria for Inclusion and Exclusion—Studies that utilized validated questionnaires to evaluate the effects of pemphigus vulgaris, pemphigus foliaceus, and/or BP on mental health were included. All research participants were 18 years and older. For the questionnaires administered, each study must have included numerical scores in the results. The studies all reported statistically significant results (P<.05), but no studies were excluded on the basis of statistical significance.

Studies were excluded if they did not use a validated questionnaire to examine quality of life (QOL) or psychological status. We also excluded database, retrospective, qualitative, and observational studies. We did not include studies with a sample size less than 20. Studies that administered questionnaires that were uncommon in this realm of research such as the Attitude to Appearance Scale or The Anxiety Questionnaire also were excluded. We did not exclude articles based on their primary language.

Results

A total of 13 studies met the inclusion criteria with a total of 1716 participants enrolled in the trials. The questionnaires most commonly used are summarized in Table 1. Tables 2 and 3 demonstrate the studies that evaluate QOL and psychological state in patients with bullous dermatoses, respectively.

The Dermatology Life Quality Index (DLQI) was the most utilized method for analyzing QOL followed by the Skindex-17, Skindex-29, and 36-Item Short Form Health Survey. The DLQI is a skin-specific measurement tool with higher scores translating to greater impairment in QOL. Healthy patients have an average score of 0.5.³ The mean DLQI scores for ABD patients as seen in Table 2 were 9.45, 10.18, 16, 10.9, and 10.1.^13-15,18,22 The most commonly reported concerns among patients included feelings about appearance and disturbances in daily activities.¹⁸ Symptoms of mucosal involvement, itching, and burning also were indicators of lower QOL.^15,18,20,22 Furthermore, women consistently had lower scores than men.^15,17,19,25 Multiple studies concluded that severity of the disease correlated with a lower QOL, though the subtype of pemphigus did not have an effect on QOL scores.^15,19,20,21 Lastly, recent onset of symptoms was associated with a worse QOL score.^15,18-20 Age, education level, and marital status did not have an effect on QOL.

To evaluate psychological state, the General Health Questionnaire (GHQ)-28 and -12 primarily were used, in addition to the Hospital Anxiety and Depression Scale; the International Classification of Diseases, Tenth Revision; the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; and the Beck Depression Inventory-II. As seen in Table 3, GHQ-12 positivity, reflecting probable minor nonpsychotic psychiatric disorders such as depression and anxiety, was identified in 47%, 39.7%, and 40% of patients with pemphigus^15,19,24; GHQ-28 positivity was seen in 77.5% of pemphigus patients.¹⁸ In the average population, GHQ positivity was found in up to 12% of patients.^26,27 Similar to the QOL scores, no significant differences were seen based on subtype of pemphigus for symptoms of depression or anxiety.^20,23

Comment

Mental Health of Patients With ABDs—Immunobullous diseases are painful, potentially lifelong conditions that have no definitive cure. These conditions are characterized by bullae and erosions of the skin and mucosae that physically are disabling and often create a stigma for patients. Across multiple different validated psychosocial assessments, the 13 studies included in this review consistently reported that ABDs have a negative effect on mental well-being of patients that is more pronounced in women and worse at the onset of symptoms.^13-25

QOL Scores in Patients With ABDs—Quality of life is a broad term that encompasses a general sense of psychological and overall well-being. A score of approximately 10 on the DLQI most often was reported in patients with ABDs, which translates to a moderate impact on QOL. Incomparison, a large cohort study reported the mean (SD) DLQI scores for patients with atopic dermatitis and psoriasis as 7.31 (5.98) and 5.93 (5.66), respectively.²⁸ In another study, Penha et al¹⁴ found that patients with psoriasis have a mean DLQI score of 10. Reasons for the similarly low QOL scores in patients with ABDs include long hospitalization periods, disease chronicity, social anxiety, inability to control symptoms, difficulty with activities of daily living, and the belief that the disease is incurable.^17,19,23 Although there is a need for increased family and social support with performing necessary daily tasks, personal relationships often are negatively affected, resulting in social isolation, loneliness, and worsening of cutaneous symptoms.

Severity of cutaneous disease and recent onset of symptoms correlated with worse QOL scores. Tabolli et al²⁰ proposed the reason for this relates to not having had enough time to find the best treatment regimen. We believe there also may be an element of habituation involved, whereby patients become accustomed to the appearance of the lesions over time and therefore they become less distressing. Interestingly, Tabolli et al¹⁷ determined that patients in the quiescent phase of the disease—without any mucosal or cutaneous lesions—still maintained lower QOL scores than the average population, particularly on the psychosocial section of the 36-Item Short Form Health Survey, which may be due to a concern of disease relapse or from adverse effects of treatment. Providers should monitor patients for mental health complications not only in the disease infancy but throughout the disease course.

Future Directions—Cause and effect of the relationship between the psychosocial variables and ABD disease state has yet to be determined. Most studies included in this review were cross-sectional in design. Although many studies concluded that bullous dermatoses were the cause of impaired QOL, Ren and colleagues²⁹ proposed that medications used to treat neuropsychiatric disorders may trigger the autoimmune antigens of BP. Possible triggers for BP have been reported including hydrochlorothiazide, ciprofloxacin, and dipeptidyl peptidase-4 inhibitors.^27,30-32 A longitudinal study design would better evaluate the causal relationship.

The effects of the medications were included in 2 cases, one in which the steroid dose was not found to have a significant impact on rates of depression²³ and another in which patients treated with a higher dose of corticosteroids (>10 mg) had worse QOL scores.¹⁷ Sung et al¹⁵ suggested this may be because patients who took higher doses of steroids had worse symptoms and therefore also had a worse QOL. It also is possible that those patients taking higher doses had increased side effects.¹⁷ Further studies that evaluate treatment modalities and timing in relation to the disease onset would be helpful.

Study Limitations—There are potential barriers to combining these data. Multiple different questionnaires were used, and it was difficult to ascertain if all the participants were experiencing active disease. Additionally, questionnaires are not always the best proxy for what is happening in everyday life. Lastly, the sample size of each individual study was small, and the studies only included adults.

Conclusion

As demonstrated by the 13 studies in this review, patients with ABDs have lower QOL scores and higher numbers of psychological symptoms. Clinicians should be mindful of this at-risk population and create opportunities in clinic to discuss personal hardship associated with the disease process and recommend psychiatric intervention if indicated. Additionally, family members often are overburdened with the chronicity of ABDs, and they should not be forgotten. Using one of the aforementioned questionnaires is a practical way to screen patients for lower QOL scores. We agree with Paradisi and colleagues¹⁹ that although these questionnaires may be helpful, clinicians still need to determine if the use of a dermatologic QOL evaluation tool in clinical practice improves patient satisfaction.

Autoimmune bullous dermatoses (ABDs) develop due to antibodies directed against antigens within the epidermis or at the dermoepidermal junction. They are categorized histologically by the location of acantholysis (separation of keratinocytes), clinical presentation, and presence of autoantibodies. The most common ABDs include pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid (BP). These conditions present on a spectrum of symptoms and severity.¹

Although multiple studies have evaluated the impact of bullous dermatoses on mental health, most were designed with a small sample size, thus limiting the generalizability of each study. Sebaratnam et al² summarized several studies in 2012. In this review, we will analyze additional relevant literature and systematically combine the data to determine the psychological burden of disease of ABDs. We also will discuss the existing questionnaires frequently used in the dermatology setting to assess adverse psychosocial symptoms.

Methods

We searched PubMed, MEDLINE, and Google Scholar for articles published within the last 15 years using the terms bullous pemphigoid, pemphigus, quality of life, anxiety, and depression. We reviewed the citations in each article to further our search.

Criteria for Inclusion and Exclusion—Studies that utilized validated questionnaires to evaluate the effects of pemphigus vulgaris, pemphigus foliaceus, and/or BP on mental health were included. All research participants were 18 years and older. For the questionnaires administered, each study must have included numerical scores in the results. The studies all reported statistically significant results (P<.05), but no studies were excluded on the basis of statistical significance.

Studies were excluded if they did not use a validated questionnaire to examine quality of life (QOL) or psychological status. We also excluded database, retrospective, qualitative, and observational studies. We did not include studies with a sample size less than 20. Studies that administered questionnaires that were uncommon in this realm of research such as the Attitude to Appearance Scale or The Anxiety Questionnaire also were excluded. We did not exclude articles based on their primary language.

Results

A total of 13 studies met the inclusion criteria with a total of 1716 participants enrolled in the trials. The questionnaires most commonly used are summarized in Table 1. Tables 2 and 3 demonstrate the studies that evaluate QOL and psychological state in patients with bullous dermatoses, respectively.

The Dermatology Life Quality Index (DLQI) was the most utilized method for analyzing QOL followed by the Skindex-17, Skindex-29, and 36-Item Short Form Health Survey. The DLQI is a skin-specific measurement tool with higher scores translating to greater impairment in QOL. Healthy patients have an average score of 0.5.³ The mean DLQI scores for ABD patients as seen in Table 2 were 9.45, 10.18, 16, 10.9, and 10.1.^13-15,18,22 The most commonly reported concerns among patients included feelings about appearance and disturbances in daily activities.¹⁸ Symptoms of mucosal involvement, itching, and burning also were indicators of lower QOL.^15,18,20,22 Furthermore, women consistently had lower scores than men.^15,17,19,25 Multiple studies concluded that severity of the disease correlated with a lower QOL, though the subtype of pemphigus did not have an effect on QOL scores.^15,19,20,21 Lastly, recent onset of symptoms was associated with a worse QOL score.^15,18-20 Age, education level, and marital status did not have an effect on QOL.

To evaluate psychological state, the General Health Questionnaire (GHQ)-28 and -12 primarily were used, in addition to the Hospital Anxiety and Depression Scale; the International Classification of Diseases, Tenth Revision; the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; and the Beck Depression Inventory-II. As seen in Table 3, GHQ-12 positivity, reflecting probable minor nonpsychotic psychiatric disorders such as depression and anxiety, was identified in 47%, 39.7%, and 40% of patients with pemphigus^15,19,24; GHQ-28 positivity was seen in 77.5% of pemphigus patients.¹⁸ In the average population, GHQ positivity was found in up to 12% of patients.^26,27 Similar to the QOL scores, no significant differences were seen based on subtype of pemphigus for symptoms of depression or anxiety.^20,23

Comment

Mental Health of Patients With ABDs—Immunobullous diseases are painful, potentially lifelong conditions that have no definitive cure. These conditions are characterized by bullae and erosions of the skin and mucosae that physically are disabling and often create a stigma for patients. Across multiple different validated psychosocial assessments, the 13 studies included in this review consistently reported that ABDs have a negative effect on mental well-being of patients that is more pronounced in women and worse at the onset of symptoms.^13-25

QOL Scores in Patients With ABDs—Quality of life is a broad term that encompasses a general sense of psychological and overall well-being. A score of approximately 10 on the DLQI most often was reported in patients with ABDs, which translates to a moderate impact on QOL. Incomparison, a large cohort study reported the mean (SD) DLQI scores for patients with atopic dermatitis and psoriasis as 7.31 (5.98) and 5.93 (5.66), respectively.²⁸ In another study, Penha et al¹⁴ found that patients with psoriasis have a mean DLQI score of 10. Reasons for the similarly low QOL scores in patients with ABDs include long hospitalization periods, disease chronicity, social anxiety, inability to control symptoms, difficulty with activities of daily living, and the belief that the disease is incurable.^17,19,23 Although there is a need for increased family and social support with performing necessary daily tasks, personal relationships often are negatively affected, resulting in social isolation, loneliness, and worsening of cutaneous symptoms.

Severity of cutaneous disease and recent onset of symptoms correlated with worse QOL scores. Tabolli et al²⁰ proposed the reason for this relates to not having had enough time to find the best treatment regimen. We believe there also may be an element of habituation involved, whereby patients become accustomed to the appearance of the lesions over time and therefore they become less distressing. Interestingly, Tabolli et al¹⁷ determined that patients in the quiescent phase of the disease—without any mucosal or cutaneous lesions—still maintained lower QOL scores than the average population, particularly on the psychosocial section of the 36-Item Short Form Health Survey, which may be due to a concern of disease relapse or from adverse effects of treatment. Providers should monitor patients for mental health complications not only in the disease infancy but throughout the disease course.

Future Directions—Cause and effect of the relationship between the psychosocial variables and ABD disease state has yet to be determined. Most studies included in this review were cross-sectional in design. Although many studies concluded that bullous dermatoses were the cause of impaired QOL, Ren and colleagues²⁹ proposed that medications used to treat neuropsychiatric disorders may trigger the autoimmune antigens of BP. Possible triggers for BP have been reported including hydrochlorothiazide, ciprofloxacin, and dipeptidyl peptidase-4 inhibitors.^27,30-32 A longitudinal study design would better evaluate the causal relationship.

The effects of the medications were included in 2 cases, one in which the steroid dose was not found to have a significant impact on rates of depression²³ and another in which patients treated with a higher dose of corticosteroids (>10 mg) had worse QOL scores.¹⁷ Sung et al¹⁵ suggested this may be because patients who took higher doses of steroids had worse symptoms and therefore also had a worse QOL. It also is possible that those patients taking higher doses had increased side effects.¹⁷ Further studies that evaluate treatment modalities and timing in relation to the disease onset would be helpful.

Study Limitations—There are potential barriers to combining these data. Multiple different questionnaires were used, and it was difficult to ascertain if all the participants were experiencing active disease. Additionally, questionnaires are not always the best proxy for what is happening in everyday life. Lastly, the sample size of each individual study was small, and the studies only included adults.

Conclusion

As demonstrated by the 13 studies in this review, patients with ABDs have lower QOL scores and higher numbers of psychological symptoms. Clinicians should be mindful of this at-risk population and create opportunities in clinic to discuss personal hardship associated with the disease process and recommend psychiatric intervention if indicated. Additionally, family members often are overburdened with the chronicity of ABDs, and they should not be forgotten. Using one of the aforementioned questionnaires is a practical way to screen patients for lower QOL scores. We agree with Paradisi and colleagues¹⁹ that although these questionnaires may be helpful, clinicians still need to determine if the use of a dermatologic QOL evaluation tool in clinical practice improves patient satisfaction.

To the Editor:

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by bilateral, symmetrical, proximal muscle weakness and classic cutaneous manifestations.¹ Patients with antibodies directed against melanoma differentiation–associated gene 5, MDA5, have a distinct presentation due to vasculopathy with more severe cutaneous ulcerations, palmar papules, alopecia, and an elevated risk of rapidly progressive interstitial lung disease.² A ferritin level greater than 1600 ng/mL portends an increased risk for pulmonary disease and therefore can be of prognostic value.³ Further, patients with anti-MDA5 DM are at a lower risk of malignancy and are more likely to test negative for antinuclear antibodies in comparison to other patients with DM.^2,4

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome, is a potentially lethal condition whereby uncontrolled activation of histiocytes in the reticuloendothelial system causes hemophagocytosis and a hyperinflammatory state. Patients present with fever, splenomegaly, cytopenia, and hyperferritinemia.⁵ Autoimmune‐associated hemophagocytic syndrome (AAHS) describes HLH that develops in association with autoimmune conditions, most commonly systemic lupus erythematosus and adult-onset Still disease. Cases reported in association with DM exist but are few in number, and there is no standard-of-care treatment.⁶ We report a case of a woman with anti-MDA5 DM complicated by HLH and DM-associated liver injury.

A 50-year-old woman presented as a direct admit from the rheumatology clinic for diffuse muscle weakness of 8 months’ duration, 40-pound unintentional weight loss, pruritic rash, bilateral joint pains, dry eyes, dry mouth, and altered mental status. Four months prior, she presented to an outside hospital and was given a diagnosis of probable Sjögren syndrome and autoimmune hepatitis vs drug-induced liver injury. At that time, a workup was notable for antibodies against Sjögren syndrome–related antigen A, anti–smooth muscle antibodies, and transaminitis. Ultrasonography of the right upper quadrant revealed hepatic steatosis. The patient was started on oral prednisone and pilocarpine but had been off all medications for 1 month when she presented to our hospital.

On hospital admission, physical examination revealed a violaceous heliotrope rash; a v-sign on the chest; shawl sign; palmar papules with pits at the fingertips; and periungual erythema and ulcerations along the metacarpophalangeal joints, elbows, lateral feet, and upper eyelids (Figure 1). Laboratory workup showed the following results: white blood cell count, 4100/μL (reference range, 4000–11,000/μL); hemoglobin, 11.6 g/dL (reference range, 12–16 g/dL); platelet count, 100,000/μL (reference range, 150,000–450,000/μL); lactate dehydrogenase, 510 U/L (reference range, 80–225 U/L); alkaline phosphatase (ALP), 766 U/L (reference range, 30–120 U/L); alanine aminotransferase (ALT), 88 U/L (reference range, 10–40 U/L); aspartate aminotransferase (AST), 544 U/L (reference range, 10–40 U/L); total bilirubin, 4.2 mg/dL (reference range, 0.3–1.0 mg/dL); direct bilirubin, 3.7 mg/dL (reference range, 0.1–0.3 mg/dL); aldolase, 20.2 U/L (reference range, 1–7.5 U/L), creatine kinase, 180 U/L (reference range, 30–135 U/L); γ-glutamyltransferase (GGT), 2743 U/L (reference range, 8–40 U/L); high sensitivity C-reactive protein, 122.9 mg/L (low-risk reference range, <1.0 mg/L); triglycerides, 534 mg/dL (reference range, <150 mg/dL); ferritin, 3784 ng/mL (reference range, 24–307 ng/mL); antinuclear antibody, negative titer; antimitochondrial antibody, negative titer; soluble IL-2 receptor (CD25), 7000 U/mL (reference range, 189–846 U/mL); anti-Sjögren syndrome–related antigen A antibody, positive.

To the Editor:

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by bilateral, symmetrical, proximal muscle weakness and classic cutaneous manifestations.¹ Patients with antibodies directed against melanoma differentiation–associated gene 5, MDA5, have a distinct presentation due to vasculopathy with more severe cutaneous ulcerations, palmar papules, alopecia, and an elevated risk of rapidly progressive interstitial lung disease.² A ferritin level greater than 1600 ng/mL portends an increased risk for pulmonary disease and therefore can be of prognostic value.³ Further, patients with anti-MDA5 DM are at a lower risk of malignancy and are more likely to test negative for antinuclear antibodies in comparison to other patients with DM.^2,4

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome, is a potentially lethal condition whereby uncontrolled activation of histiocytes in the reticuloendothelial system causes hemophagocytosis and a hyperinflammatory state. Patients present with fever, splenomegaly, cytopenia, and hyperferritinemia.⁵ Autoimmune‐associated hemophagocytic syndrome (AAHS) describes HLH that develops in association with autoimmune conditions, most commonly systemic lupus erythematosus and adult-onset Still disease. Cases reported in association with DM exist but are few in number, and there is no standard-of-care treatment.⁶ We report a case of a woman with anti-MDA5 DM complicated by HLH and DM-associated liver injury.

A 50-year-old woman presented as a direct admit from the rheumatology clinic for diffuse muscle weakness of 8 months’ duration, 40-pound unintentional weight loss, pruritic rash, bilateral joint pains, dry eyes, dry mouth, and altered mental status. Four months prior, she presented to an outside hospital and was given a diagnosis of probable Sjögren syndrome and autoimmune hepatitis vs drug-induced liver injury. At that time, a workup was notable for antibodies against Sjögren syndrome–related antigen A, anti–smooth muscle antibodies, and transaminitis. Ultrasonography of the right upper quadrant revealed hepatic steatosis. The patient was started on oral prednisone and pilocarpine but had been off all medications for 1 month when she presented to our hospital.

On hospital admission, physical examination revealed a violaceous heliotrope rash; a v-sign on the chest; shawl sign; palmar papules with pits at the fingertips; and periungual erythema and ulcerations along the metacarpophalangeal joints, elbows, lateral feet, and upper eyelids (Figure 1). Laboratory workup showed the following results: white blood cell count, 4100/μL (reference range, 4000–11,000/μL); hemoglobin, 11.6 g/dL (reference range, 12–16 g/dL); platelet count, 100,000/μL (reference range, 150,000–450,000/μL); lactate dehydrogenase, 510 U/L (reference range, 80–225 U/L); alkaline phosphatase (ALP), 766 U/L (reference range, 30–120 U/L); alanine aminotransferase (ALT), 88 U/L (reference range, 10–40 U/L); aspartate aminotransferase (AST), 544 U/L (reference range, 10–40 U/L); total bilirubin, 4.2 mg/dL (reference range, 0.3–1.0 mg/dL); direct bilirubin, 3.7 mg/dL (reference range, 0.1–0.3 mg/dL); aldolase, 20.2 U/L (reference range, 1–7.5 U/L), creatine kinase, 180 U/L (reference range, 30–135 U/L); γ-glutamyltransferase (GGT), 2743 U/L (reference range, 8–40 U/L); high sensitivity C-reactive protein, 122.9 mg/L (low-risk reference range, <1.0 mg/L); triglycerides, 534 mg/dL (reference range, <150 mg/dL); ferritin, 3784 ng/mL (reference range, 24–307 ng/mL); antinuclear antibody, negative titer; antimitochondrial antibody, negative titer; soluble IL-2 receptor (CD25), 7000 U/mL (reference range, 189–846 U/mL); anti-Sjögren syndrome–related antigen A antibody, positive.

To the Editor:

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by bilateral, symmetrical, proximal muscle weakness and classic cutaneous manifestations.¹ Patients with antibodies directed against melanoma differentiation–associated gene 5, MDA5, have a distinct presentation due to vasculopathy with more severe cutaneous ulcerations, palmar papules, alopecia, and an elevated risk of rapidly progressive interstitial lung disease.² A ferritin level greater than 1600 ng/mL portends an increased risk for pulmonary disease and therefore can be of prognostic value.³ Further, patients with anti-MDA5 DM are at a lower risk of malignancy and are more likely to test negative for antinuclear antibodies in comparison to other patients with DM.^2,4

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome, is a potentially lethal condition whereby uncontrolled activation of histiocytes in the reticuloendothelial system causes hemophagocytosis and a hyperinflammatory state. Patients present with fever, splenomegaly, cytopenia, and hyperferritinemia.⁵ Autoimmune‐associated hemophagocytic syndrome (AAHS) describes HLH that develops in association with autoimmune conditions, most commonly systemic lupus erythematosus and adult-onset Still disease. Cases reported in association with DM exist but are few in number, and there is no standard-of-care treatment.⁶ We report a case of a woman with anti-MDA5 DM complicated by HLH and DM-associated liver injury.

A 50-year-old woman presented as a direct admit from the rheumatology clinic for diffuse muscle weakness of 8 months’ duration, 40-pound unintentional weight loss, pruritic rash, bilateral joint pains, dry eyes, dry mouth, and altered mental status. Four months prior, she presented to an outside hospital and was given a diagnosis of probable Sjögren syndrome and autoimmune hepatitis vs drug-induced liver injury. At that time, a workup was notable for antibodies against Sjögren syndrome–related antigen A, anti–smooth muscle antibodies, and transaminitis. Ultrasonography of the right upper quadrant revealed hepatic steatosis. The patient was started on oral prednisone and pilocarpine but had been off all medications for 1 month when she presented to our hospital.

On hospital admission, physical examination revealed a violaceous heliotrope rash; a v-sign on the chest; shawl sign; palmar papules with pits at the fingertips; and periungual erythema and ulcerations along the metacarpophalangeal joints, elbows, lateral feet, and upper eyelids (Figure 1). Laboratory workup showed the following results: white blood cell count, 4100/μL (reference range, 4000–11,000/μL); hemoglobin, 11.6 g/dL (reference range, 12–16 g/dL); platelet count, 100,000/μL (reference range, 150,000–450,000/μL); lactate dehydrogenase, 510 U/L (reference range, 80–225 U/L); alkaline phosphatase (ALP), 766 U/L (reference range, 30–120 U/L); alanine aminotransferase (ALT), 88 U/L (reference range, 10–40 U/L); aspartate aminotransferase (AST), 544 U/L (reference range, 10–40 U/L); total bilirubin, 4.2 mg/dL (reference range, 0.3–1.0 mg/dL); direct bilirubin, 3.7 mg/dL (reference range, 0.1–0.3 mg/dL); aldolase, 20.2 U/L (reference range, 1–7.5 U/L), creatine kinase, 180 U/L (reference range, 30–135 U/L); γ-glutamyltransferase (GGT), 2743 U/L (reference range, 8–40 U/L); high sensitivity C-reactive protein, 122.9 mg/L (low-risk reference range, <1.0 mg/L); triglycerides, 534 mg/dL (reference range, <150 mg/dL); ferritin, 3784 ng/mL (reference range, 24–307 ng/mL); antinuclear antibody, negative titer; antimitochondrial antibody, negative titer; soluble IL-2 receptor (CD25), 7000 U/mL (reference range, 189–846 U/mL); anti-Sjögren syndrome–related antigen A antibody, positive.