INTRODUCTION — Fixed drug eruption (FDE) is a distinctive type of cutaneous drug reaction that characteristically recurs in the same locations upon re-exposure to the offending drug. Acute FDE usually presents with a single or a small number of dusky red or violaceous plaques that resolve leaving postinflammatory hyperpigmentation (picture 1A-C). Rare severe atypical variants of FDE, including multiple, nonpigmenting, and generalized bullous variants, share clinical features with Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).
FDE will be discussed in this topic. Other types of drug eruptions are discussed separately. (See "Drug eruptions" and "Exanthematous (maculopapular) drug eruption" and "Lichenoid drug eruption (drug-induced lichen planus)" and "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis".)
EPIDEMIOLOGY — Cutaneous skin reactions occur in approximately 2 to 3 percent of patients taking drugs. FDEs are less common than exanthematous (morbilliform) eruptions, which are estimated to account for up to 95 percent of cutaneous drug reactions [1-3]. In an analysis of electronic health records of 2.7 million patients from a large United States health system, the prevalence of FDE was 0.003 percent . FDE occurs in all age groups without sex predilection. In pediatric series of cutaneous drug reactions, FDEs accounted for approximately 5 to 22 percent of cases [5-7]. In a Pakistani study of 193 adult patients with cutaneous adverse drug reactions, 5.7 percent had FDE.
ETIOLOGY AND PATHOGENESIS
Eliciting drugs — Many drugs may induce FDE. The frequency with which individual drugs cause FDE varies over time and from country to country, depending upon drug availability and rates of consumption. Drugs most frequently associated with FDE include [8-10]:
●Antibacterial agents (trimethoprim-sulfamethoxazole, tetracyclines, penicillins, quinolones, dapsone)
●Nonsteroidal anti-inflammatory drugs (NSAIDs; acetylsalicylic acid, ibuprofen, naproxen, mefenamic acid)
Rare cases of FDE induced by levocetirizine, a second-generation antihistamine, have also been reported [11,12]. Foods and food additives are also uncommon causes of FDE [13-18].
FDE can be induced by drugs with a chemical structure similar to the causative drug (cross-reactivity). There are isolated reports of FDE lesions reactivated by chemically unrelated drugs, a phenomenon known as polysensitivity [19,20].
There are several case reports of FDE following the administration of coronavirus disease 2019 (COVID-19) vaccines, in the absence of any prior exposure to medications [21-24]. This suggests that FDE lesions can be evoked by activation of the innate immune system.
Immunologic mechanisms — Intraepidermal CD8+ T cells are thought to have a key role in mediating the localized epidermal lesion that characterizes FDE . CD8+ T cells with an effector-memory phenotype are abundantly detected along the dermoepidermal junction in established FDE lesions and persist in healed (resting) FDE lesions long after the clinical resolution (picture 2A-B) [25-29].
Sequential analysis of FDE lesions before and after rechallenge with the causative drug demonstrated that intraepidermal CD8+ T cells are directly involved in epidermal damage (picture 3) . CD8+ T cells remain quiescent but in a primed state in healed FDE lesions unless the causative drug is readministered. Upon rechallenge, CD8+ T cells are activated to release interferon gamma and cytotoxic granules such as granzyme B and perforin [28-30]. Mast cells also contribute to the activation of intraepidermal T cells via the induction of cell adhesion molecules on the surrounding keratinocytes, through the action of tumor necrosis factor alpha .
The activation of intraepidermal T cells is sufficient for triggering the reaction but insufficient to cause the extensive tissue damage observed in fully evolved lesions. Cytokines and/or adhesion molecule-mediated recruitment of CD4+ T cells, CD8+ T cells, and neutrophils may contribute to tissue damage in fully developed FDE lesions.
In the late stage of the immune response, CD4+CD25+Foxp3+ regulatory T (Treg) cells are recruited into the lesion and participate in the homeostatic control of the immune reaction. The majority of the expanded or activated cell populations responsible for epidermal damage are eventually removed from tissue by apoptosis. However, a proportion of intraepidermal CD8+ T cells is prevented from undergoing apoptosis by IL-15 secreted by basal keratinocytes and persists at the injury site as a memory T cell population [30,31].
HISTOPATHOLOGY — Histologically, FDE is the prototype of a lichenoid tissue reaction with pigmentary incontinence (accumulation of melanin in the upper dermis and dermal macrophages) . In florid lesions, major features include hydropic degeneration of basal keratinocytes, dyskeratotic cells scattered in the epidermis, lymphocytic infiltration of the dermis, and dermal melanophages. The hair follicles and acrosyringia (the intraepidermal portions of the sweat gland duct) also may be involved. In some lesions, the exocytosis of lymphocytes is marked, mimicking Pautrier microabscesses of mycosis fungoides.
Healed hyperpigmented lesions show pigmentary incontinence and a mild perivascular inflammatory infiltrate.
The pathologic changes occurring in a resting lesion after re-exposure to the offending drug have been documented by sequential biopsies :
●Resting FDE lesions are characterized by a small number of resident memory phenotype CD8+ lymphocytes aligned along the epidermal side of the dermoepidermal junction (picture 2A-B). The overlying epidermis appears normal (picture 3).
●Two to three hours after rechallenge, the lymphocytes originally adhering to the basal layer move upward to the lower one-half of the epidermis while preserving the epidermal structures.
●Twenty-four to 48 hours after rechallenge, the typical changes of interface dermatitis can be seen, including vacuolar degeneration of keratinocytes, dermal lymphocytic infiltrate extending upward into the epidermis, and dermal pigmentary incontinence. The extent of epidermal damage is highly variable, ranging from intercellular edema and dyskeratotic cells scattered in the epidermis to confluent epidermal necrosis resembling TEN.
Several atypical histologic reaction patterns have been described in FDE, including a neutrophilic reaction, leukocytoclastic vasculitis, and nonpigmenting fixed drug eruption (NPFDE) [33-36]. In NPFDE, the epidermal changes are mild or absent and a superficial perivascular infiltrate of lymphocytes and eosinophils without melanophages is seen in the upper reticular dermis. In generalized bullous fixed drug eruption (GBFDE), the histologic features of the blister area closely resemble those seen in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN; full-thickness necrosis of the epidermis without pigmentary incontinence) .
CLINICAL MANIFESTATIONS — FDE typically presents with well-demarcated, round to oval, dusky red to brown/black macules that may evolve into edematous plaques with or without vesiculation or blistering (picture 1A, 1D). Lesions are usually solitary but may occur in small groups.
Systemic symptoms, such as fever and malaise, are usually absent. Pruritus and a burning or stinging sensation are common. However, the estimated frequency of these findings is not known because they are not consistently reported in case series.
FDE may occur anywhere on the body. Sites of predilection include the lips, genitalia, perianal area, hands, and feet . On mucosal areas, erosions and ulcers may develop (picture 4). On the oral mucosa, lesions are predominantly located on the dorsum of the tongue and on the hard palate (picture 5) . FDE occasionally develops at the site of an antecedent trauma (eg, insect bite, burn, venipuncture) [40,41]. FDE often develops at sites of previous herpesvirus infection or reactivation (eg, herpes simplex or zoster lesions).
Acute lesions generally appear 30 minutes to 8 hours after drug administration but can occur up to two weeks after drug exposure [9,42]. After discontinuation of the offending drug, lesions resolve spontaneously in 7 to 10 days, leaving a persistent gray/brown or slate gray postinflammatory hyperpigmentation (picture 1C).
Upon re-exposure to the offending drug, lesions typically recur in the same site, but new lesions may develop elsewhere (picture 6). After one or more localized eruptions, FDE rarely may evolve into a bullous generalized form mimicking Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (picture 7). (See 'Generalized fixed drug eruption' below and 'Generalized bullous fixed drug eruption' below.)
CLINICAL VARIANTS — FDE rarely may present with atypical features that mimic other skin diseases such as erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), cellulitis, paronychia, neutrophilic dermatosis, or large plaque parapsoriasis.
Erythema multiforme-like fixed drug eruption — FDE may present with targetoid lesions that mimic erythema multiforme (picture 8). In contrast to erythema multiforme, these lesions have only two concentric zones of color with a darker, dusky hue in the center. (See "Erythema multiforme: Pathogenesis, clinical features, and diagnosis", section on 'Clinical manifestations'.)
Generalized fixed drug eruption — The typical lesions are multiple and disseminated and involve the trunk and extremities, sparing the mucosal and the semimucosal areas (picture 9). Generalized FDE may be difficult to distinguish clinically and histologically from erythema dyschromicum perstans (picture 10) .
Generalized bullous fixed drug eruption — Generalized bullous fixed drug eruption (GBFDE) is an extremely rare form of FDE characterized by widespread red or brown macules or plaques with overlying large flaccid bullae (picture 7) . Systemic symptoms, such as fever, malaise, or arthralgias may be present.
Patients with GBFDE can be misdiagnosed as having SJS/TEN, but in GBFDE mucosal involvement is usually absent or mild and the clinical course is favorable with rapid resolution in 7 to 14 days after drug discontinuation [45-47]. However, the prognosis of GBFDE may be unfavorable in older patients, particularly in those with comorbidities.
In a case-control study including patients with GBFDE (age range 68 to 84 years) and matched controls with SJS/TEN, the mortality rate among patients with GBFDE was 22 percent, similar to that observed among patients with SJS/TEN with the same amount of skin detachment . (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Clinical presentation'.)
Nonpigmenting fixed drug eruption — Nonpigmenting fixed drug eruptions (NPFDEs) have been described in a small number of patients, most often in association with the administration of pseudoephedrine. NPFDE presents with large solitary or multiple, well-circumscribed erythematous plaques that resolve without postinflammatory hyperpigmentation [33,49].
A severe form of NPFDE, characterized by disseminated, large, symmetrical plaques and systemic symptoms, may be misdiagnosed as SJS/TEN. However, in NPFDE, erythema has relatively little tendency to coalesce, and systemic symptoms are milder (in contrast with TEN).
Other variants — Other rare forms of FDE have been described in isolated reports and include [50-52]:
●FDE presenting with acute paronychia
●FDE presenting with a linear distribution reminiscent of herpes zoster
●FDE mimicking large plaque parapsoriasis
Clinical — The diagnosis of FDE in its typical presentation is usually straightforward, based upon lesion morphology and history:
●Single or a small number of round or oval, demarcated, erythematous or hyperpigmented macules or plaques located most often on the lips, genitalia, and extremities (picture 1A-B, 1E).
●History of drug intake in the hours or days preceding the eruption. The medication history should be taken in great detail and include all types of medications and routes of administration, since patients tend to overlook medications that they have been taking sporadically over years. (See "An approach to the patient with drug allergy", section on 'Identification of the suspect drug'.)
●History of recurrence in the same sites following the administration of the same drug or a chemically related drug.
Biopsy — A skin biopsy for histopathologic examination may be warranted in the following circumstances:
●Unusual clinical presentation (eg, generalized or bullous FDE) that raises the suspicion of severe drug reaction
●Presence of systemic symptoms (eg, fever, malaise) that raise suspicion of severe drug reaction
●When the diagnosis is uncertain (eg, negative medication history)
Histologic findings that support the diagnosis of FDE include hydropic degeneration of the basal layer, pigmentary incontinence, single necrotic keratinocytes (dyskeratotic cells) in the upper layers of the epidermis, and a dermal inflammatory infiltrate predominantly composed of lymphocytes. In generalized bullous fixed drug eruption (GBFDE), the examination of a biopsy taken from the blister area reveals full-thickness necrosis of the epidermis without pigmentary incontinence. (See 'Histopathology' above.)
Provocation tests — Systemic (oral challenge) and topical (patch testing) provocation tests can be performed to identify the culprit drug when history is unclear or multiple medications are suspected [8,31].
Systemic provocation — Oral challenge with the suspected drug induces the reactivation of a resting FDE lesion. In most cases, oral challenge is preferred to patch testing because it reproduces the conditions of exposure.
Oral challenge is contraindicated in patients with a history of generalized FDE. In patients without generalized FDE, oral challenge is considered relatively safe because the cutaneous response is localized, and the risk of a severe reaction is low. In a series of 450 patients with FDE, oral challenge with the suspected drug produced pruritus in 10 percent of patients, fever in 0.9 percent, and generalized urticaria in 0.7 percent, but no more severe adverse effects .
However, neither the appropriate dose of the suspected drug sufficient to induce a mild reaction nor the timing of the test after the resolution of the initial eruption has been standardized. Our approach is to perform the test two to four weeks after the resolution of the eruption, starting with one-tenth of a single therapeutic dose and gradually increasing the amount every 12 to 24 hours up to one single therapeutic dose. Such a gradual approach may not be necessary in patients with a single or a few lesions. In a prospective series of 93 patients with FDE, oral challenge was started with one-half of the therapeutic dose; if no reaction was elicited, a full dose was given .
A flare-up reaction occurring within 30 minutes to 8 hours of the oral challenge within a resting FDE lesion is considered a positive test response (picture 6) .
Patch testing — Patch testing can also be used to confirm the diagnosis if oral testing cannot be performed (eg, patients with a history of generalized FDE) or if the patient or parent/caregiver refuses an oral challenge. Patch testing can be performed by applying the suspected drug to an old FDE lesion to elicit a local reaction. Patch testing is generally considered to be safe because the reaction is localized.
There is no standardized method for patch testing in FDE. Various drug concentrations and application modalities (eg, single open, repeated open, or occlusive) have been used in several series of patients [9,10,54,55].
Our approach is to use the commercially available drug mixed in petrolatum or diluted in water at the concentration of approximately 10 to 20 percent. The drug is applied to the target area in open or occlusive modality. The development of erythema with or without induration that starts within 24 hours and lasts for at least 6 hours is considered a positive reaction (picture 11) .
The sensitivity of patch testing for FDE is usually poor, with positive reactions obtained in approximately 40 percent of cases, unless the patch test is applied to the site of a previous reaction [56,57]. False negative results may occur when testing drugs with limited ability to penetrate into the skin or when FDE is caused by a drug metabolite . False positive reactions may be observed with drug concentrations higher than 20 percent due to patch test sensitization. (See "Patch testing", section on 'Active sensitization'.)
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of FDE includes:
●Erythema multiforme – Erythema multiforme (EM) is rarely induced by drugs. The number, distribution, and morphology of lesions help to differentiate EM from FDE. Target lesions consisting of three components (a dusky central area or blister, a dark red inflammatory zone surrounded by a pale ring of edema, and an erythematous halo) are the hallmark of EM (picture 12). They are generally numerous and symmetrically distributed on the extremities. Mucosal lesions are present in many cases (EM majus) (picture 13). (See "Erythema multiforme: Pathogenesis, clinical features, and diagnosis", section on 'Clinical manifestations'.)
●Stevens-Johnson syndrome/toxic epidermal necrolysis – Generalized bullous fixed drug eruption (GBFDE) may sometimes be difficult to differentiate from Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (picture 14). However, in SJS/TEN, lesions have a less defined border than FDE lesions with a tendency to coalesce; mucous membranes (eg, oral, conjunctival) are involved in over 90 percent of cases (picture 15); and patients have systemic symptoms and rapid disease progression.
The histologic features in the early stage of SJS/TEN are similar to those of GBFDE ; however, as the disease progresses, full thickness epidermal necrosis with skin detachment above the basement membrane becomes evident. In most patients, GBFDE resolves rapidly in 7 to 14 days after drug discontinuation [45,46]. The course of SJS/TEN is generally longer than in GBFDE and complications and sequelae (eg, sepsis, organ failure, late ophthalmic and pulmonary complications) are frequent. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis" and "Stevens-Johnson syndrome and toxic epidermal necrolysis: Management, prognosis, and long-term sequelae", section on 'Long-term sequelae'.)
●Bullous pemphigoid – Bullous pemphigoid (BP) typically occurs in patients older than 60 years and is frequently preceded by a prodromal phase characterized by pruritic inflammatory plaques resembling urticaria. The typical skin lesions of BP are large, tense blisters that rupture and heal spontaneously without scarring (picture 16). Histology reveals a subepidermal blister with a dermal infiltrate of eosinophils, neutrophils, and lymphocytes (picture 17). Direct immunofluorescence of perilesional skin shows linear IgG and/or linear C3 staining along the basement membrane zone (picture 18), which is absent in FDE. The diagnosis of BP can be confirmed by enzyme-linked immunosorbent assay demonstrating circulating autoantibodies against the bullous pemphigoid antigens BP180 NC16A domain and BP230. (See "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid", section on 'Diagnosis' and "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid".)
●Large plaque parapsoriasis – Large plaque parapsoriasis may resemble the pigmented patches of FDE (picture 19A-B). A skin biopsy is necessary to clarify the diagnosis. Histology reveals epidermal hyperplasia (or atrophy in poikilodermatous areas) and a dermal lymphocytic infiltrate that can become band-like at the dermal epidermal junction and show epidermotropism (exocytosis of small lymphocytes into the epidermis). Multiple FDE mimicking parapsoriasis, due to repeated flares by different drugs at the same site, has been reported in a patient with hepatitis C virus (HCV) infection, suggesting that multiple drug hypersensitivity could be induced by antiviral immune responses that cross-react to multiple drugs, but not by HCV per se . (See "Parapsoriasis (small plaque and large plaque parapsoriasis)".)
●Autoimmune progesterone dermatitis – Autoimmune progesterone dermatitis (APD) is a rare disorder caused by autoantibodies to endogenous luteal phase progesterone . It presents in the days preceding the menstrual cycle as urticarial, eczematous, vesiculobullous, or EM-like mucocutaneous lesions. Rarely, APD may present with features of FDE (picture 20). (See "Progestogen hypersensitivity".)
●Aphthous stomatitis – Oral FDE may present as aphthous-like lesions. One report describes the development of a painful, large, pseudomembranous ulcer on the dorsal aspect of the tongue with an adjacent, yellowish-white patch . (See "Recurrent aphthous stomatitis".)
Drug withdrawal and avoidance — Discontinuation of the offending drug is the most important aspect of management of FDE. After drug discontinuation, lesions resolve without treatment in a few days leaving postinflammatory hyperpigmentation.
Patients should be advised to avoid the offending drug and chemically related drugs and be provided with a written list of the generic and brand names of the culprit drug and possibly of cross-reactive drugs. More information is available about beta-lactam antibiotics and is reviewed elsewhere. (See "Penicillin allergy: Delayed hypersensitivity reactions", section on 'Fixed drug eruption'.)
Symptomatic treatment — The treatment of FDE is largely symptomatic and aimed at the relief of pruritus. The efficacy of symptomatic therapies for the treatment of FDE has not been evaluated in randomized trials. However, their use is based on clinical experience and indirect evidence of benefit in patients other pruritic skin conditions (see "Pruritus: Therapies for localized pruritus"):
●For patients with a single or small number of lesions, we suggest medium- to high-potency topical corticosteroids (groups 1 to 3 (table 1)) and systemic antihistamines. Topical corticosteroids are applied two times per day for 7 to 10 days.
●For patients with generalized FDE or generalized bullous fixed drug eruption (GBFDE), particularly if systemic symptoms are present, a short course of moderate dose systemic corticosteroids (eg, prednisone 0.5 to 1 mg/kg per day for three to five days) may be beneficial, although studies supporting its use are lacking.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Drug allergy and hypersensitivity".)
SUMMARY AND RECOMMENDATIONS
●Definition and etiology – Fixed drug eruption (FDE) is a cutaneous drug reaction that characteristically recurs in the same locations upon re-exposure to the offending drug. Antibacterial sulfonamides, antibiotics, nonsteroidal antiinflammatory drugs, analgesics, and hypnotics are the most frequent causes of FDE. (See 'Introduction' above and 'Eliciting drugs' above.)
•Typical features – FDE typically presents with solitary round to oval, dusky red to brown/black macules that may evolve into edematous plaques or bullae (picture 1A-B, 1D). Sites of predilection include the lips, genitalia, perianal area, and extremities. Acute lesions usually develop 30 minutes to 8 hours after drug administration and resolve spontaneously in 7 to 10 days, leaving a persistent gray/brown or slate gray postinflammatory hyperpigmentation (picture 1C). (See 'Clinical manifestations' above.)
•Atypical features – In rare cases, FDE may present with atypical features, including generalized bullous fixed drug eruption (GBFDE) and nonpigmenting fixed drug eruption (NPFDE), that mimic more severe drug eruptions, such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (picture 7). (See 'Clinical variants' above.)
●Diagnosis – The diagnosis of FDE in its typical presentation is usually straightforward, based upon lesion morphology and history. Histologic examination of a skin biopsy is helpful in establishing the diagnosis in cases with unusual clinical features. Systemic or topical provocation tests may be helpful in identifying the culprit drug when history is unclear or multiple medications are suspected. (See 'Diagnosis' above.)
●Management – Discontinuation and avoidance of the offending drug is the most important aspect of management of FDE (see 'Drug withdrawal and avoidance' above):
•For patients with a single lesion or small number of lesions, we suggest symptomatic treatment with topical corticosteroids and systemic antihistamines (Grade 2C). Medium- to high-potency topical corticosteroids (groups 1 to 3 (table 1)) are applied twice daily for 7 to 10 days.
•For patients with generalized FDE or GBFDE, particularly if systemic symptoms are present, a short course of systemic corticosteroids (eg, prednisone 0.5 to 1 mg/kg per day for three to five days) may be beneficial, although studies supporting their use are lacking. (See 'Symptomatic treatment' above.)
1 : Drug-induced cutaneous reactions. A report from the Boston Collaborative Drug Surveillance Program on 15,438 consecutive inpatients, 1975 to 1982.
4 : Drug Hypersensitivity Reactions Documented in Electronic Health Records within a Large Health System.
12 : A case of levocetirizine-induced fixed drug eruption and cross-reaction with piperazine derivatives.
13 : Fixed Food Eruption Caused by Actinidia arguta (Hardy Kiwi): A Case Report and Literature Review.
17 : Fixed eruption due to quinine in tonic water: a case report with high-performance liquid chromatography and ultraviolet A analyses.
19 : Polysensitivity in fixed drug eruption due to a novel drug combination-independent lesions due to piroxicam and cotrimoxazole.
23 : Generalized bullous fixed drug eruption after Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccination.
28 : T cell receptor (TCR) repertoire and function of human epidermal T cells: restricted TCR V alpha-V beta genes are utilized by T cells residing in the lesional epidermis in fixed drug eruption.
29 : Direct evidence for interferon-gamma production by effector-memory-type intraepidermal T cells residing at an effector site of immunopathology in fixed drug eruption.
30 : In vivo dynamics of intraepidermal CD8+ T cells and CD4+ T cells during the evolution of fixed drug eruption.
33 : Nonpigmenting fixed drug eruption as a distinctive reaction pattern: examples caused by sensitivity to pseudoephedrine hydrochloride and tetrahydrozoline.
35 : Neutrophilic fixed drug eruption caused by naproxen: a real entity or a stage in the histopathologic evolution of the disease?
40 : Trauma-localized fixed drug eruption: involvement of burn scars, insect bites and venipuncture sites.
43 : Fixed drug eruption presenting as erythema dyschromicum perstans: a flare without taking any medications.
47 : Generalized bullous fixed drug eruption is distinct from Stevens-Johnson syndrome/toxic epidermal necrolysis by immunohistopathological features.
48 : Prognosis of generalized bullous fixed drug eruption: comparison with Stevens-Johnson syndrome and toxic epidermal necrolysis.
49 : Nonpigmenting fixed drug eruption as a possible abortive variant of toxic epidermal necrolysis: immunohistochemical and serum cytokine analyses.
58 : Multiple Fixed Drug Eruption Mimicking Parapsoriasis en Plaque in a Patient with Hepatitis C Virus Infection.
59 : Catamenial dermatoses associated with autoimmune, inflammatory, and systemic diseases: A systematic review,.
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