Linagliptin-Associated Alopecia and Bullous Pemphigoid

Someili, Ali; Azzam, Khalid; Hilal, Mohannad Abu

doi:10.12890/2019_001207

Cited by 7 publications

(8 citation statements)

References 23 publications

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“…[ 7 ] that described bullous pemphigoid and alopecia in a patient taking linagliptin, a member of the DPP-IV inhibitors. [ 8 ] The patient responded in a similar manner on discontinuation of the drug as our patient. A post-marketing surveillance study conducted in Japan offered corresponding results as our report of alopecia on increasing the dose to 40 mg once daily.…”

Section: Discussionsupporting

confidence: 69%

Teneligliptin-induced hair loss: A case report

Agrawal

Gautam

Pursnani

et al. 2020

J Family Med Prim Care

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Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the common phenotype of hyperglycemia secondary to various pathophysiologic mechanisms that include reduced insulin secretion, decreased glucose utilization, and increased glucose production. Individuals suffering from Type 2 DM (T2DM) tend to be at a higher risk for the development of both micro as well as macrovascular complications. Management strategy includes an armamentarium of drugs and lifestyle modifications. 35 years old male diagnosed with T2DM was started on a fixed-dose combination of 20 mg Teneligliptin and 1 g metformin once daily. After consuming this dose for a month, he observed no reduction in his blood sugar levels and consequently escalated the dose to twice daily without any consultation or supervision. Subsequently, on next visit OPD his blood sugar was controlled, however, he complained of hair loss from the scalp. This complaint was resolved with the discontinuation of Teneligliptin.

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Section: Discussionsupporting

confidence: 69%

Teneligliptin-induced hair loss: A case report

Agrawal

Gautam

Pursnani

et al. 2020

J Family Med Prim Care

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“…Additionally, the temporal relationship between the introduction of the gliptin agent and the manifestation of BP, and its remission after withdrawal of the drug with mild therapeutic intervention, led to the conclusion that DPP-4i are the culprit agents. Since then, the association of DPP-4i and BP has been continuously reported through case reports, small case series [ 54 – 61 ], observational studies [ 33 ], and pharmacovigilance database analysis [ 34 ]. In a recent retrospective case–control study, DPP-4i are associated to threefold increase of BP risk.…”

Section: Dpp-4i-induced Bpmentioning

confidence: 99%

“…BP230 is an intracellular component of hemidesmosomes that belongs to the plakin proteins family; the N-terminal domain and the globular C-terminal domain of BP230 are the targets of IgG antibodies in BP [ 4 ]. In DPP-4i-induced BP, most of the IgG autoantibodies target preferentially epitopes in the mid portion of the extracellular domain of BP180 [ 74 ], including the LAD-1 and the C-terminal domain [ 54 , 74 ], and not the juxtamembranous NC16A domain [ 16 , 69 , 74 ]. Nonetheless, IgG autoantibodies against BP 180 NC16A identical to those found in classical BP have been identified in certain cases of DPP-4i-induced BP [ 68 ]; it has been hypothesized that they probably arise during the course of the disease as a result of an epitope spreading phenomenon [ 69 , 70 ].…”

Section: Dpp-4i-induced Bpmentioning

confidence: 99%

“…The direct immunofluorescence (DIF) study, done in normal-appearing perilesional skin, demonstrates IgG and complement C3 deposition in a linear band at the dermal–epidermal junction: these finding are identical in both DPP-4i induced and conventional BP and area paramount diagnostic feature. Indirect immunofluorescence (IIF) documents the presence of IgG circulating autoantibodies in the patient's serum by showing on human salt-split skin IgG staining on the epidermal side of the blister [ 3 , 54 ]. The IIF aspect in DPP-4i-induced BP is indistinguishable from that seen in spontaneous BP.…”

Section: Dpp-4i-induced Bpmentioning

confidence: 99%

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Bullous pemphigoid in diabetic patients treated by gliptins: the other side of the coin

et al. 2021

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Bullous pemphigoid (BP) is the most common autoimmune bullous skin disease that affects primarily patients older than 60 years. The majority of BP cases are spontaneous, but BP can also be triggered by certain drugs’ exposures. Since 2011, a growing number of observations has been reporting cases of BP in Type 2 diabetic patients. These forms have been linked to the use of a new category of anti-diabetic drugs called dipeptidyl peptidase inhibitors (DPP-4i) or gliptins, but to date, the exact pathophysiological mechanisms underlying this association are not completely elucidated. Although conventional and gliptin-associated BP are thought to share similar clinical and histopathological features, our thorough review of the most recent literature, shows that these 2 forms are quite distinct: DPP-4-i-associated BP seems to appear at an earlier age than spontaneous BP, it may manifest either as a noninflammatory or inflammatory phenotype, while the conventional form presents with a typical inflammatory phenotype. Additionally, an important distinctive histological feature was recently shown in Gliptin-associated BP: these forms may present a less significant eosinophils infiltrate in the upper dermis of peri-blister lesions compared to the skin of patients with spontaneous BP, and this seems a specific feature of the clinically non-inflammatory forms. In accordance with previous literature, we found that the direct immunofluorescence (DIF) gives identical findings in both DPP-4i-associated and conventional forms of BP which is an IgG and complement C3 deposition as a linear band at the dermal–epidermal junction in perilesional skin. Indirect immunofluorescence shows the presence of IgG circulating autoantibodies in the patient's serum which titer does not differ between spontaneous and DPP-4i-associated BP, while the specificity of these autoantibodies, may be different in spontaneous, induced non-inflammatory and induced inflammatory forms, epitope spreading phenomenon seems to play a role in determining these specificities. Further research, based on integrated epidemiological, clinical, histo-immunological and pharmacogenomic approaches, may give more insight into these forms of BP. This combined approach will allow to better define BP endotypes and to unveil the mechanism of spontaneous or drug-induced breakage of the immunotolerance to skin self-antigens.

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“…In addition to BP, various other DPP-4 inhibitor-associated dermatoses have been described in the literature, including psoriasiform dermatitis, maculopapular rash, photodermatitis, eczematous rash, lichen planus, and even alopecia areata and mucositis. [5][6][7][8][9][10][11] Since the first case report in 2011 of DPP-4 inhibitorassociated BP, various publications have implicated DPP-4 inhibitors in the pathogenesis of BP. 12 DPP-4 inhibitors have been associated with a 3.2-fold increase in risk of developing BP, with vildagliptin and linagliptin being the most common inducing agents.…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl peptidase‐4 inhibitor‐associated cutaneous eruptions: a retrospective observational study

Duraisamy

Jagadeesan

Eapen

et al. 2022

Clin Experimental Derm

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Summary Background Dipeptidyl peptidase (DPP)‐4 plays a complex role in immune regulation and its inhibition can have effects on the pathogenesis of various skin diseases. Studies have shown that DPP‐4 inhibitors are associated with an increased risk of bullous pemphigoid (BP). Aim To analyse the clinical and histopathological features of cutaneous adverse events in patients on DPP‐4 inhibitors. Methods We performed a retrospective review of patients with suspected DPP‐4 inhibitor‐associated cutaneous adverse events, at a tertiary teaching hospital from 1 January 2017 to 31 December 2020. Exclusion criteria included previous history of chronic skin disease and lack of histopathological reports or follow‐up records. The clinical characteristics, latency period, Naranjo Adverse Drug Reaction Probability Scale and clinical outcomes were evaluated. Results In total, 18 patients (10 men, 8 women; mean age 68.6 years, range 38–89 years) were included. The DPP‐4 inhibitors used were teneligliptin (n = 6), vildagliptin (n = 6), sitagliptin (n = 4), linagliptin (n = 1) and saxagliptin (n = 1). The mean interval between therapy initiation and lesion onset was 8.8 months (range 1–24 months). The dermatoses noted were BP (n = 12; 66.6%), lichenoid dermatitis (n = 4; 22.2%), psoriasiform dermatitis (n = 1; 5.6%) and spongiotic dermatitis (n = 1; 5.6%). Eight patients (44.4%) had necrotic keratinocytes as one of the distinct histological features. Causality assessment using the Naranjo scale rated the causative role of DPP‐4 inhibitors as ‘possible’ in all patients. Of the 18 patients, 11 (61.1%) noted improvement in their condition following discontinuation of DPP‐4 inhibitors, with 5 having complete remission within 6 months of stopping the drug. Conclusion DPP‐4 inhibitor‐associated dermatoses are not necessarily limited to BP. It is necessary to recognize the possibility of other dermatoses in patients on DPP‐4 inhibitors as drug substitution/cessation may improve disease morbidity.

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Linagliptin-Associated Alopecia and Bullous Pemphigoid

Cited by 7 publications

References 23 publications

Teneligliptin-induced hair loss: A case report

Teneligliptin-induced hair loss: A case report

Bullous pemphigoid in diabetic patients treated by gliptins: the other side of the coin

Dipeptidyl peptidase‐4 inhibitor‐associated cutaneous eruptions: a retrospective observational study

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