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ORIGINAL ARTICLE Table of Contents  
Ahead of print publication
Mortality and cause of death in patients with dermatologic diseases: An 11-year record-based observational study


1 Department of Dermatology, Skin Diseases and Leishmaniasis Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Dermatology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Biostatics and Epidemiology, School of Public Health, Isfahan University of Medical Sciences, Isfahan, Iran

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Date of Submission24-Aug-2022
Date of Decision14-Oct-2022
Date of Acceptance15-Nov-2022
Date of Web Publication09-Jan-2023
 

  Abstract 


Background: Information on the cause of death is critical in guiding decisions on health infrastructure. However, there is a relative paucity of mortality data in patients with dermatologic diseases. Objectives: We aim to assess the overall mortality from dermatological disorders in a third-level university hospital which serves as a dermatology referral center. Methods: A retrospective medical note review of patients with dermatologic diseases who died during an 11-year period (from March 2008 to February 2020) was undertaken. Results: There were 63 death cases out of 2810 admissions for patients with dermatologic diseases (crude mortality 2.24%). The average age was 61.8 years and the male-to-female ratio was 2.3. Cutaneous malignancies (53.96%) were the primary causes of death, followed by drug reactions (23.8%). Among skin cancers, squamous cell carcinoma (SCC; 47.05%) and melanoma (35.29%) were the leading causes of death. Toxic epidermal necrolysis (53.33%) was the leading cause of death among drug reactions. Sepsis (30.74%) was the most common immediate cause of mortality in this series. A large fraction of patients (73%) had significant underlying comorbidities. Conclusion: The principal cause of mortality was cutaneous malignancies (mainly SCC and melanoma) followed by drug reactions. Sepsis was the most common immediate cause of death.

Keywords: Cause of death, dermatology, epidemiology, hospital records, mortality


How to cite this URL:
Saber M, Faghihi G, Seyedghafouri SA, Hosseini SM. Mortality and cause of death in patients with dermatologic diseases: An 11-year record-based observational study. Dermatol Sin [Epub ahead of print] [cited 2023 Feb 4]. Available from: https://www.dermsinica.org/preprintarticle.asp?id=367365





  Introduction Top


Dermatology is a large outpatient clinical and surgical specialty, but it plays an important role in the care of inpatients admitted to hospitals.[1] Several dermatological conditions are life-threatening and mortality is an inevitable complication. Although few studies have been conducted to ascertain the disease-specific mortality rates such as cutaneous malignancies, pemphigus vulgaris, and Stevens–Johnson syndrome–toxic epidermal necrolysis (SJS-TEN), mortality of dermatological disorders in general have been rarely studied.[2],[3],[4] Review of mortality pattern of dermatologic diseases aids to improve patient care and facilitates implementation of trends that improve the mortality rate of patients with dermatologic diseases in the future. In addition, it guides decisions on health infrastructure and the provision of public hospitals' medical services. Despite the important role of mortality studies, death causes in dermatology patients is understudied due to causes other than skin cancers.[5],[6],[7]

In this retrospective study, we aim to assess the overall mortality from dermatological disorders in a third-level university hospital which serves as a dermatology referral center in central Iran. This review can benefit management practices by highlighting the most common mortality causes in patients with cutaneous diseases to focus prevention efforts. In addition, such data may help direct the expenditure of the national health budget toward health-care priorities.


  Methods Top


The study was conducted at the Alzahra Hospital (AH), an 800-bed tertiary care center in Isfahan, Iran, which serves more than 3 million people from several provinces in central Iran. We performed a retrospective study of patients admitted to the Dermatology Division of AH over a period of 11 years from March 20, 2008, to February 19, 2020, when the COVID outbreak started in Iran.

The current study was approved by Isfahan University's Institutional Review Board and Ethics Committee (IR.MUI.MED.REC.1398.675).

Data were retrieved from the medical records library of the hospital. The medical certifications of cause of death records were used to obtain data on the mortality of patients due to cutaneous diseases.

The clinical documentation, laboratory findings, and medications were extracted from electronic medical records of deceased patients with cutaneous diseases. Two experienced clinicians reviewed and abstracted the data and completed the questionnaires. Patients with incomplete or missing data in their records were excluded from the study.

Data were analyzed using SPSS statistical software,Version 22.0 (IBM Corp., Armonk, NY, USA). A P < 0.05 was considered statistically significant.


  Results Top


During the study, 2810 patients with dermatologic conditions were admitted to the hospital, of which 63 patients died. Hence, the mortality rate of patients with cutaneous diseases was 2.24%.

Demographic data

Of the 63 patients who died 69.84% (n = 44) were male and 30.15% (n = 19) were female. Male to female ratio was approximately 2.3. The mean age was 61.8 years (range 1–98 years). The maximum number of mortality (n = 15) occurred in the age group of 61–70 years, accounting for 23.8% of total deaths, followed by 13 deaths (20.63%) in the age group of 81–90 years. The minimum number of mortalities was found to be in the age group <10 years. [Figure 1] shows a histogram of the decadal age group by sex.
Figure 1: Number of deceased patients by age and sex.

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Clinical diagnosis

Based on a review of medical records, the diagnosis was assigned to one of the following categories: (1) cutaneous malignancies, (2) drug reactions, (3) immunobullous/inflammatory dermatosis, and (4) miscellaneous dermatosis.

Cutaneous malignancies (34 cases, 53.96%) comprised the most frequent cause of death followed by drug reaction, immunobullous/inflammatory dermatosis and miscellaneous dermatosis accounting for 15 (23.8%), 8 (12.69%), and 6 (9.52%) deaths, respectively [Figure 2].
Figure 2: Distribution of the cause of death in the dermatologic patients.

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Among the skin malignancies, squamous cell carcinoma (SCC) was the most lethal, accounting for 16 deaths (16/34, 47.05%) followed by melanoma (12 cases, 35.29%), Merkel cell carcinoma (4 cases, 11.76%), and basal cell carcinoma (2 cases, 5.88%) [Table 1].
Table 1: Distribution of the cause of death in the dermatologic patients

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TEN was found to be the most common drug reaction (8/15 cases, 53.33%), followed by SJS (5/15 cases, 33.33%) and finally by drug-induced erythroderma (2/15 cases, 13.33%). Several drugs were identified as probable etiologic agents in these cases. Antibiotics (n = 7/15, 46.66%) were the most common causative drugs followed by anticonvulsants (n = 5/15, 33.33%) and NSAIDs (n = 2/15, 13.33%). The most common etiologic agents were meropenem and phenytoin. Other patients (2/15, 13.33%) had multiple agents involved and a single etiologic agent not be identified.

The most frequent causes of death were psoriasis (n = 4/8, 50%) and pemphigus vulgaris (n = 3/8, 37.5%) among patients with vesiculobullous/inflammatory dermatosis. Of the other 8, 1 patient (12.5%) died from bullous pemphigoid.

Deaths associated with pyoderma gangrenosum (n = 2/6, 33.3%), cellulitis (n = 2/6, 33.3%), leishmaniasis (n = 1/6, 16.66%), and anthrax (n = 1/6, 16.66%) were classified as a separate category and labeled as miscellaneous cause of death.

Trend of cause of death

To ascertain the rate of mortality change from cutaneous diseases, we assessed mortality trends using the nonparametric Mann–Kendall statistical test.[8],[9] The trend slope was determined using the Sen's method.[10] Our trend analyses indicated a statistically significant increasing trend at 90% confidence level (P = 0.0796) with a slope of 0.34 person/year in mortality due to cutaneous malignancies. The other cutaneous diseases did not show statistically significant trends.

Duration of stay in hospital

Forty-three serious patients were admitted to the emergency department and the others were admitted to the dermatology ward. The duration of hospital stays ranged from 1 day to 102 days (mean 12.39 days).

Immediate cause of death

Sepsis was the most common immediate cause of death, accounting for 20 cases (30.74%). Blood culture was positive with Acinetobacter baumannii in 3 cases (15%), Methicillin resistance Staphylococcus aureus (MRSA), Enterococcus and Escherichia coli each in 1 patient (5%). In 14 cases blood culture was negative, however, MRSA, Pseudomonas aeruginosa and Enterococcus isolated from the colonized skin lesions of 4, 3, and 1 patients, respectively. There were 7 cases whose diagnosis remained clinical, named culture-negative sepsis.

The mortality rate due to sepsis was highest in patients with TEN and SCC, each of them similarly was underlying diseases of 25% cases. Pemphigus vulgaris, BCC, and melanoma, each of which account for 10% [Table 2].
Table 2: Principal causes of death in the 63 patients

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The second most frequent cause of death was electrolyte imbalance (8 cases, 12.69%). TEN, metastatic SCC, and melanoma were the most common underlying disease, each accounting for 25% of cases.

Next came death from acute renal failure and thromboembolic events, each accounting for 6 cases (% 9.52). Pneumonia was the cause of death in 5 cases (7.93%). The results showed similar percentage of dead patients due to cardiovascular events, lung failure and cerebral edema (4.76%). A detailed distribution cause of death is presented in [Figure 3].
Figure 3: Distribution of deceased patients according to the immediate cause of death, from 2008 to 2020. CV: Cerebrovascular, DIC: Disseminated intravascular coagulation, TTP: Thrombotic thrombocytopenic purpura.

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Transfer of patients to the intensive care unit

There were 20 inpatient transfers to the intensive care unit (ICU). The male-to-female ratio by percentage was 70%–30%. The mean age of patients was 57 ± 23.71.

By far, the most frequent dermatologic diagnosis of patients who transferred to the ICU was TEN/SJS (7 Cases, 35%). After that, metastatic SCC and melanoma separately account for 20% of total admissions to the ICU. The most frequent cause of death in patients who were admitted to the ICU was sepsis and renal failure, each of which accounts for 20% of cases. Electrolyte imbalance was the second most common cause of death (15%). [Table 3] provides an overview of data of patients who transferred to the ICU.
Table 3: Data of patients who transferred to the intensive care unit

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Comorbidities

A large proportion of patients had significant underlying comorbidities. The mean ± standard deviation number of comorbidities present at admission was 1.39 ± 1.06 (range: 0–4). The most frequent comorbidities were hypertension (n = 23, 36.5%), ischemic heart disease (n = 12, 19.04%), diabetes mellitus (n = 10, 15.87%), and cerebrovascular accident (n = 6, 9.52%).


  Discussion Top


In the present study, we reviewed the databases of 63 dead patients, spanning over 11 years (2008-2020). Due to COVID-19 outbreak, we did not consider the data from February 20, 2020 onward. The mortality rate was 2.24% and the maximum number of deaths (15 death cases) occurred in 61–70 years of age group. The mortality rate in males (69.84%) was higher than females (30.15%).

The death rate found in our study was slightly lower than that of Journet-Tollhupp et al. in France[11] and Nair et al. in India[5] with 3.7%–5.3% and 3.58%, far lower than Keita et al.[12] 7.9% in Guinea and Ecra et al.[7] 10.26% in Sub-Saharan Africa. Perhaps worthy of emphasis was the finding of a relatively similar mortality rate (2.25%) due to dermatologic diseases in Brazil reported by de Paula Samorano-Lima et al.[13] [Table 4].
Table 4: Literature review: comparison with similar studies

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The low mortality rate in the current study may be attributed to the following reasons: First, patients received advanced medical care. Moreover, low case-fatality rate due to high hospitalization of non-ill patients and academic interest of dermatologists for hospitalization of patients. Finally, biological, socio-cultural, and economic factors are major contributors to the health disparities and higher mortality rate in African countries (Guinea and Sub-Sahara).

In the current study, cutaneous malignancies were the most common cause of death, accounting for more than half of all deaths in skin diseases. SCC (47%) and melanoma (35%) were the leading cause of cancer-related deaths. In our study, SCC alone was responsible for about one-quarter of all deaths. The majority of these lesions were located on the scalp or face, and a significantly smaller number of tumors were placed on the finger. About 80% of skin cancers reported in men, where the number of cases was approximately 4 times higher in men than women. It could be inferred that men use less sun protection behaviors and potentially have outdoor occupation than women. In addition, it may be related to wearing hijab by women in Iran.

In like manner, in the study reported by Journet-Tollhupp et al. in France[11] and Keita et al.[12] in Guinea, cutaneous malignancies were the leading cause of death. However, melanoma and Kaposi sarcoma were the most commonly encountered skin malignancies in France and Guinea, respectively.

Kaposi sarcoma is among the most common cancers in Africa, and its geographic restriction suggests environmental cofactors.[16] Cutaneous melanoma is a skin cancer nearly exclusively occurring in white skin population, including in European countries. It is the most common cause of skin cancer-related death in developed countries.[17]

Although in India and Brazil immunobullous diseases were responsible for the majority of certified cause of death in dermatologic patients,[5],[6],[13],[15] it occurs in small percentage of our patients (6.34%). Remarkably, we did not record any mortality due to pemphigus vulgaris since 2011. It might due to the fact that from 2011 we started using intravenous immunoglobulin and then rituximab for severe and refractory pemphigus vulgaris patients.

The second most common cause of death was drug reaction. During the 11 years covered by this survey, 5.33% of all hospitalized dermatologic patients died due to adverse cutaneous drug eruption. This was a high mortality rate considering the fact that previous studies reported only about 2% of adverse cutaneous reactions are severe and very few are fatal.[18] In the current study, TEN was found to be the most common drug reaction followed by SJS. The most common etiologic agents were antibiotics. However, phenytoin was the most frequent single agent. Arbitrary use of drugs, especially antibiotics is one of the most important factors about this issue and educational intervention helps in this way.

In respect to the immediate cause of death, sepsis was the leading cause of mortality about one-third of all deaths. In addition, sepsis was the main cause of death in critically ill patients who were transferred to the ICU.

These results were in accordance with the similar findings in some earlier studies.[6],[13],[15]

In our series, sepsis was the major cause of death among patients with SCC (31.25%), BCC (100%), TEN (50%), and pemphigus vulgaris (66.66%) [Table 2]. Interestingly, among the patients who died of sepsis, about one third had positive blood culture results and A. baumannii was the most common bacterial strain. Of the 14 negative blood samples (defined as culture-negative sepsis), positive cutaneous culture was detected in about half of cases and the most frequent pathogens were MRSA followed by P. aeruginosa.

However, in the study by de Paula Samorano-Lima et al.[13] and Chowdhury et al.[6] S. aureus was the most common organism isolated.

Electrolyte imbalance and renal failure both were detected mostly in patients with cutaneous malignancies account for more than one-quarter of cause of death among these patients. In addition, death due to central nervous system complications including cerebral edema, hemorrhage, and infection were detected only in patients who died of SCC or melanoma.

In the current study, a large proportion of patients had significant comorbidities. The most frequent comorbidity was hypertension followed by ischemic heart disease. Only 26.98% (n = 17) of the 63 cases had no underlying comorbidity. This finding is in agreement with previous reports that comorbidity in general is significantly related to mortality.[19]

The small sample size and retrospective design are the main limitations in our study. In addition, the cases were extracted from medical records library entered by the patient's physician on or near the date of death and error in determining cause of death may be occurred. Further studies involving a greater number of hospitals would be required to increase the external validity of our data.


  Conclusions Top


The mortality rate in our series was 2.24% and it was more than two-fold higher in men than women (69.8% vs. 30.1%, respectively). Cutaneous malignancies were the most frequent cause of death followed by drug reactions. Given that almost 80% of all skin cancers can be prevented by reasonable behavior, especially UV protection education plays a fundamental role at the community level. In addition, minimizing improper antibiotic use according to published guidelines could also reduce risk of drug reactions.

Finally, we believe that mortality studies of sufficient size and duration supply new information and generate hypothesis that can form the basis for further exploration and elimination of risk factors contributing to the increased mortality in dermatologic patients.

Acknowledgments

The authors would like to thank Dr. Ali Saber for data analysis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Correspondence Address:
Mina Saber,
Department of Dermatology, Skin Diseases and Leishmaniasis Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan
Iran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ds.DS-D-22-00134



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