Grover's disease (transient acantholytic dermatosis)

Meet the patient — the itchy man in bed 14

A 68-year-old man, day five after a hemiarthroplasty for a fractured neck of femur, is scratching so hard at his central chest and upper back that the nurses have called you. He is hot under the occlusive dressing, febrile from a urinary tract infection, on his back for most of the day, and has erupted over forty-eight hours with crops of firm, discrete, intensely itchy red papules on the central chest and upper back. Face, palms, soles and mouth are spared. You write "drug reaction" first, then look again.[1]

Hold two questions in mind for every truncal itch in an older inpatient: is the face, mouth, palm or sole involved? (no, in Grover's — and that one fact rules out Darier and pemphigus at the bedside) and what is the DIF going to show? (negative in Grover's, positive in pemphigus). Answer those two and the rest of the topic slots into place.[1]

What "transient" really means — and the misnomer trap

Grover's disease is best read as a reactive acantholytic dermatosis, not a discrete entity. Ralph Grover named it "transient acantholytic dermatosis" in 1970 because his original cases vanished within weeks; the label stuck even though up to forty per cent of patients in modern series run a chronic or relapsing course for months to years.[2][4][5]

The defining histology is focal acantholysis — suprabasal keratinocytes lose their desmosomal grip, the basal layer stays pinned to the basement membrane like a row of tombstones, and individual rounded acantholytic cells float free in a small cleft. The same trigger that does this once can do it again in a new focus, which is why the biopsy often shows several patterns at once.[1]

The diagnosis rests on a triad every registrar should be able to recite: typical morphology and distribution, typical demographic (older man), and a punch biopsy with focal acantholysis plus a negative DIF. The negative DIF is the single most discriminating test in the workup, because it cleanly separates Grover's from pemphigus.[1]

The four-pattern fingerprint — and why DIF is your tie-breaker

Grover's sits inside a family of acantholytic disorders, and the family tree is exam gold. In ICD-11 it lives under Disorders of skin appendages → Other specified disorders of skin (ED7Y) with the inclusion term "Transient acantholytic dermatosis". The useful clinical split is by mechanism and DIF, not by gene.[1]

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The classic clinical sub-classification you can name at the bedside: classical (transient) Grover's, persistent acantholytic dermatosis beyond 6–12 months, and the histology-led variants — Darier-like, pemphigus-like, Hailey-Hailey-like, spongiotic, bullous, eczematous, follicular and photo-distributed.[1]

Who gets it — and the triggers you can recite on a ward round

Grover's is uncommon but not rare — roughly 1–2 per cent of dermatology referrals for truncal papular eruptions in temperate climates. The median age is the sixth to seventh decade, and men outnumber women about three to one. The single most useful epidemiological fact, though, is the bedridden inpatient: a hospitalised, post-operative or ITU patient is roughly twice as likely to develop it as an age-matched ambulant person.[4][2]

The trigger list is short and examinable. The high-yield ones — heat and sweating (hot weather, hot baths, occlusive clothing, electric blankets, fever), prolonged bed rest and immobility (orthopaedics, stroke, ITU), xerosis and winter (paradoxically, the European peak), sun exposure (photo-distributed variant), and the rare but mandatory haematological or solid-organ malignancy that flags paraneoplastic acantholysis. Drug triggers (IL-4, penicillamine, 5-fluorouracil) exist but causation is rarely proven.[1]

The SERCA axis — one biology, three diseases

The defining histological event is acantholysis — the loss of intercellular adhesion between suprabasal keratinocytes. Distinguish it cleanly from spongiosis (intercellular oedema that widens desmosomal gaps without rupturing them); both can sit in the same Grover's biopsy, and they are different mechanisms.[1]

The unifying concept is the calcium-pump–desmosome axis. Darier's is broken at ATP2A2 (SERCA2, the endoplasmic-reticulum calcium pump); Hailey-Hailey at ATP2C1 (SPCA1, the secretory-pathway pump). Both load Ca²⁺ into intracellular stores, and that high ER calcium is required for desmosomal cadherins — desmogleins, desmocollins, plakoglobin, plakophilin — to fold and traffic to the cell border. Recent work shows Grover's lesions share the same downstream signatures — reduced plakoglobin and desmoglein at keratinocyte borders — without the germline mutation. Heat, sweat and ageing transiently cripple the same axis that Darier breaks permanently.[1][6]

Two further observations fill out the story. Sweat-duct occlusion is the local "second hit" that converts subclinical fragility into visible acantholysis — explaining the truncal predilection (high sweat-gland density) and the bed-rest link. Xerosis and barrier dysfunction explain the winter peak: a defective stratum corneum drives trans-epidermal water loss, inflammation and pruritus, with acantholysis as a secondary phenomenon.[1]

Why four patterns in one biopsy? Each focus of acantholysis begins as a small suprabasal cleft; as it evolves, the surrounding epidermis may develop dyskeratosis (Darier-like, with corps ronds and grains), extend through the full spinous layer (Hailey-Hailey-like "dilapidated brick wall"), stay suprabasal without dyskeratosis (pemphigus-like) or become spongiotic. The four patterns are four morphological stages of one process, not four diseases.[1][3]

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At the bedside — what you see, and the three things you must exclude

The classical picture is unmistakable once seen. Acute to subacute onset of intense pruritus, crops of 1–3 mm firm, discrete, erythematous to red-brown papules and papulovesicles on the central chest, upper back and clavicular region, sometimes spreading to flanks, mid-back and proximal limbs. Face, scalp, palms, soles and oral mucosa are spared — and that absence is the diagnostic clue that rules out Darier and pemphigus at the bedside.[1]

Know the named atypical variants because they generate traps in exams: bullous or vesiculobullous (mimics bullous pemphigoid, but suprabasal and DIF-negative), eczematous or spongiotic-predominant (misdiagnosed as eczema until biopsy), follicular (mimics folliculitis), photo-distributed (sun-exposed chest after intense UV), herpetiform (mimics dermatitis herpetiformis), universal or erythrodermic (think paraneoplastic), and Hailey-Hailey-like widespread (flexural accentuation). Onset is acute to subacute; "transient" describes the median course of six weeks to six months.[1]

The differential — when "Grover's" is the wrong word

Grover's has a wide differential because the phenotype — itchy truncal papulovesicles in an older adult — is shared by eczema, scabies, drug eruptions and several primary acantholytic disorders. Histology is the tie-breaker; the negative DIF is the single most discriminating test.[1]

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The bedside round — three lines of evidence, one fresh biopsy

The diagnosis is built on three lines of evidence: the clinical pattern (typical morphology and distribution in a typical demographic with a typical trigger), the bedside exclusion of close mimics (scabies, eczema, contact dermatitis, folliculitis), and the histological confirmation by punch biopsy from a fresh, intact papulovesicle with negative DIF.[1]

Run the bedside checklist on every suspected case. Examine the whole trunk and document lesion count; explicitly note absence of face, scalp, oral, palmar, plantar and nail involvement (your rule-out for Darier and pemphigus); inspect flexures for Hailey-Hailey-like variants; check finger webs, wrists, waistline and genitals for scabies burrows with dermoscopy (the "delta-wing" sign); look at hair and nails for Darier clues (V-nicks, longitudinal lines); elicit the Nikolsky sign (negative in Grover's, positive in pemphigus); and take a trigger history — room temperature, hot baths, electric blanket, occlusive clothing, recent sun, hospitalisation, surgery, ITU, dialysis, new drugs, fever, weight loss, night sweats.[1]

Dermoscopy is non-specific but supportive — a star-like or "crown" pattern of a brownish-red centre surrounded by a whitish halo with a fine peripheral pigment network and occasional red globules. It overlaps with several spongiotic and acantholytic dermatoses, so it confirms nothing on its own.[1]

The punch biopsy that ends the argument

First-line is two punches from one anaesthetised field. Send the diagnostic papulovesicle in formalin for H&E, and a perilesional punch for DIF in Michel's or Zeus medium (or saline-soaked gauze if transfer is under two hours). DIF is negative in Grover's; intercellular IgG/C3 redefines the diagnosis as pemphigus, linear IgG/C3 at the basement membrane as bullous pemphigoid, granular IgA at dermal papillae as dermatitis herpetiformis.[1][3]

Second-line is selective. Serum anti-desmoglein 1 and 3 ELISA in atypical, persistent or bullous cases, or where DIF is borderline or unavailable (negative in Grover's); bacterial swab if impetiginisation is suspected; viral PCR for HSV/VZV if grouped vesicles suggest eczema herpeticum; skin scraping and dermoscopy for scabies; KOH for candidal or dermatophyte infection; patch testing if contact dermatitis is plausible and persistent.[1]

Selective workup for associated disease is reserved for persistent or refractory cases — full blood count, peripheral smear and LDH for haematological malignancy; urea, creatinine and eGFR for renal failure or dialysis; HIV serology in atypical, widespread or persistent adult disease; age-appropriate cancer screening (PSA, mammography, CT chest/abdomen/pelvis) only if paraneoplastic acantholytic dermatosis is genuinely suspected (explosive onset, severe pruritus, older adult, weight loss, B-symptoms, resistance to multiple therapies); ATP2A2 or ATP2C1 sequencing if Darier or Hailey-Hailey cannot be excluded.[1]

Histopathology — four patterns, one negative DIF

The hallmark is focal acantholysis — small, discrete, well-circumscribed foci in which suprabasal keratinocytes have lost cohesion and float free in a cleft. The basal layer stays pinned to the basement membrane as a row of tombstones (as in pemphigus vulgaris, but in Grover's the change is focal, not confluent). The acantholysis may be accompanied by spongiosis and a perivascular lymphocytic infiltrate in the papillary dermis, with scattered eosinophils and neutrophils.[1]

The four classical patterns, often coexisting in the same biopsy, are reproduced verbatim because examiners expect them:[1][3]

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Direct immunofluorescence is negative in all four patterns — the single most useful test in the workup. Intercellular IgG/C3 redefines the diagnosis as pemphigus; basement-membrane staining as bullous pemphigoid; granular IgA at dermal papillae as dermatitis herpetiformis. Immunohistochemistry (research or equivocal cases only) shows reduced plakoglobin and desmoglein 1/3 at lesional keratinocyte borders, supporting the desmosomal-target model.[1][6]

The management ladder — environment first, retinoid last

Grover's is almost never a dermatological emergency. The exceptions are narrow but real. Eczema herpeticum (Kaposi varicelliform eruption) — HSV superinfection of excoriated papules, with painful punched-out erosions, fever and lymphadenopathy — means admit, start empirical IV aciclovir 5 mg/kg 8-hourly (10 mg/kg 8-hourly if immunocompromised) pending PCR, and add staphylococcal cover. Exfoliative erythroderma is rare but real — admit for temperature control, fluids and a mid-potency topical steroid to the whole body. Secondary bacterial sepsis from extensive impetiginisation needs IV flucloxacillin.[1]

For everyone else, the immediate symptomatic bundle is what the patient remembers: cool the room to 20–22 °C with light cotton clothing and no occlusive layers; emollient (50:50 white soft paraffin/liquid paraffin, or a ceramide-based moisturiser) at least twice daily and after every wash; a sedating antihistamine at night (hydroxyzine 25 mg or doxepin 10–25 mg) to break the itch-scratch cycle; a mid-potency topical corticosteroid (betamethasone valerate 0.1% cream) twice daily to inflamed papules for two to four weeks, stepping down to hydrocortisone 1%; stop or substitute any suspected drug; and address the underlying cause of bed rest — mobilise, turn two-hourly, use a cooling mattress.[1]

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The stepwise ladder, committed to memory:[1]

1. Trigger avoidance — cool environment, light clothing, emollient, stop offending drugs, mobilise the bedridden patient.
2. Topical corticosteroid — mid-potency betamethasone valerate 0.1% or mometasone furoate 0.1% twice daily for 2–4 weeks; step down to hydrocortisone 1% as disease settles.
3. Antihistamine for pruritus — non-sedating (cetirizine 10 mg, loratadine 10 mg) by day, sedating (hydroxyzine 25 mg, doxepin 10–25 mg) at night.
4. Topical calcineurin inhibitor — tacrolimus 0.1% ointment or pimecrolimus 1% cream twice daily as a steroid-sparing agent and for face and flexures.
5. Oral tetracycline — doxycycline 100 mg BD or minocycline 100 mg BD for 4–12 weeks as the first systemic option in persistent disease; the mechanism is anti-inflammatory, not antimicrobial.
6. Phototherapy — NB-UVB 311 nm two to three times weekly for 8–12 weeks for widespread disease, especially when tetracyclines fail or are not tolerated.
7. Oral retinoid — isotretinoin 10–20 mg daily or acitretin 25 mg daily for severe or refractory persistent acantholytic dermatosis; monitor LFTs, lipids, pregnancy status.
8. Refractory or severe cases — short oral prednisolone 0.5 mg/kg/day tapered over 4–6 weeks as a bridge; biologics (case reports of omalizumab, dupilumab) are experimental.[1]

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The subtypes you must name in a viva

Persistent (chronic) acantholytic dermatosis is, by convention, disease continuing beyond 6–12 months with relapses; the histology is identical and the ladder is the same, with a lower threshold for systemic therapy. Always re-evaluate the differential — pemphigus foliaceus, paraneoplastic acantholysis, scabies and chronic eczema hide here.[1]

Bullous or vesiculobullous Grover's has tense vesicles or small bullae predominating. The diagnostic dilemma is bullous pemphigoid in the elderly, and the discriminator is the negative DIF and the suprabasal (not subepidermal) split. Treatment is identical to classical Grover's; tetracyclines are particularly effective.[1]

Eczematous or spongiotic-predominant Grover's has erythema, weeping and scaling with spongiotic dominant histology; it is commonly misdiagnosed as eczema and only biopsy reveals the truth. Follicular or infundibular Grover's has papules centred on hair follicles (mimics folliculitis; culture negative). Photo-distributed Grover's has crops on sun-exposed chest, upper back and arms after intense sun, with summer seasonality — sun avoidance, broad-spectrum sunscreen and the standard ladder.[1]

Grover's in the ITU, post-operative or bedridden patient is the single most common clinical scenario. Immobility, occlusive dressings, sweating under drapes, xerosis of elderly skin and polypharmacy create the perfect storm. Prevention — cooling mattress, two-hourly turns, daily emollient, light clothing, judicious drug review — is more effective than any active treatment once established, and the eruption usually resolves within days to weeks of remobilisation.[1]

Grover's in end-stage renal disease or haemodialysis coexists with uraemic pruritus and worsens scratching; tetracyclines are best avoided or dose-reduced in severe renal impairment, so favour aggressive emollient use and optimised dialysis. Grover's in HIV or immunosuppression carries a lower biopsy threshold and a wider differential (Kaposi sarcoma, eosinophilic folliculitis, drug eruptions, scabies, papular pruritic eruption of HIV); anti-Dsg ELISA and DIF remain negative.[1]

Paraneoplastic acantholytic dermatosis is rare but mandatory to name — explosive onset, severe and often generalised pruritus, atypical distribution, resistance to multiple therapies, most often with haematological malignancy (CLL, lymphoma, myeloma) and less often solid tumours. Workup is full blood count, peripheral smear, LDH, SPEP/immunofixation and CT chest/abdomen/pelvis. Treatment is directed at the underlying malignancy, and the eruption often improves when the tumour responds.[1]

Complications — the small list, the big trap

Disease-related complications cluster around the itch–scratch axis: pruritus and excoriation disrupt sleep and drive presentation; secondary bacterial infection (impetiginisation with Staph. aureus or streptococci) needs topical fusidic acid 2% or oral flucloxacillin 500 mg QID; eczema herpeticum needs admission and IV aciclovir; chronic scratching produces lichenification and prurigo nodularis; post-inflammatory hyper- or hypopigmentation, especially visible in Fitzpatrick IV–VI skin, can persist for months; exfoliative erythroderma is rare but a dermatological emergency with temperature dysregulation and high-output cardiac failure; chronic pruritus carries a significant psychosocial burden of sleep disturbance, anxiety and depression.[1]

The diagnostic pitfalls are where candidates lose marks. Missing pemphigus vulgaris — atypical, persistent, mucosal, or DIF not performed. Missing Darier's disease — a young patient, nail changes, or a positive family history. Missing scabies — in a hospitalised or institutionalised patient, a truncal papular eruption is more often scabies than Grover's; examine the webs and the family. Missing a drug eruption — a new drug within two to four weeks; stop and observe. Treating eczema as Grover's — chronic topical and oral steroid use in unbiopsied eczema may mask an evolving pemphigus. Misreading a mixed-pattern biopsy as pemphigus or Darier — a single-section biopsy with negative DIF and no family history is Grover's, even if some features "look like" pemphigus.[1]

Therapeutic pitfalls are equally predictable. Prolonged potent topical steroid in elderly xerotic skin — atrophy, telangiectasia, striae, and the rebound flare on cessation. Systemic corticosteroids as first-line — they work, but the disease rebounds on taper; reserve as a short bridge. Isotretinoin in women of childbearing age without adequate contraception — teratogenicity; iPLEDGE is mandatory. Phototherapy in a patient with a history of skin cancer or photosensitive lupus — carcinogenesis and flare risk. Missing the underlying trigger — the disease recurs as long as heat, sweat, occlusion or a drug continues.[1]

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Prognosis and disposition — fifty per cent gone, ten per cent stuck

About 50 per cent of classical Grover's resolves spontaneously within six weeks to six months. A further 30–40 per cent have a relapsing-remitting course that may continue for years, and about 10 per cent have truly persistent disease requiring ongoing therapy. The disease does not shorten life expectancy; mortality, when it occurs, is from associated conditions — malignancy, ITU admission — rather than from Grover's itself. Once disease extends beyond six months, the probability of complete resolution falls; about half of persistent cases continue to relapse over years. Continued heat, sweat or occlusion exposure, advanced age, xerosis, immunosuppression and underlying malignancy all worsen the prognosis.[1]

Discharge is outpatient, with GP follow-up at four to six weeks to review trigger avoidance and treatment response, dermatology review at eight to twelve weeks if no improvement (sooner if atypical, persistent or worsening), and a safety-net for: widespread painful erosions or fever (eczema herpeticum), facial/mucosal/palmoplantar/nail involvement (re-diagnosis), persistent disease beyond six months (escalation), or new systemic symptoms (paraneoplastic screen).[1]

Special populations — the elderly, the dialysed, the pregnant

The elderly (over 70) are the dominant demographic. Polypharmacy, xerosis, immobility and chronic medical conditions (heart failure, renal failure, malignancy) all contribute. Tailor the ladder: low-to-mid potency topical steroid (avoid super-potent in the very elderly), emollient-based regimen, sedating antihistamine at night for sleep, tetracyclines in reduced dose if renal function is borderline, phototherapy if mobile. Avoid systemic corticosteroids — falls, infection, glycaemic decompensation.[1]

Renal failure and haemodialysis make tetracyclines problematic (doxycycline is partly renally excreted, minocycline is hepatotoxic). Use reduced-dose doxycycline, alternative systemic agents, or aggressive topical and phototherapy; optimise dialysis adequacy and uraemic pruritus with emollients, gabapentin (off-label) and UV-B. HIV and immunosuppression carry a lower biopsy threshold and a broader differential; anti-Dsg ELISA and DIF remain negative in Grover's.[1]

Post-operative and bedridden patients are the most common scenario, and prevention is the most effective intervention — cool ambient temperature, light clothing, two-hourly turns, daily emollient, judicious drug review, early mobilisation. Once established, the eruption usually resolves within two to six weeks of remobilisation. Pregnancy and breastfeeding contraindicate tetracyclines (fetal teeth and bone), isotretinoin and acitretin (teratogenic); first-line is mild-to-moderate topical steroid, tacrolimus 0.1% ointment, emollient and trigger avoidance, with NB-UVB acceptable in pregnancy with appropriate shielding; loratadine and cetirizine are considered safe antihistamines. Children are rarely affected before puberty; the differential widens (scabies, papular urticaria, atopic dermatitis, Gianotti-Crosti, pityriasis rosea, miliaria) and management is conservative — emollient, trigger avoidance, hydrocortisone 1%; avoid tetracyclines and retinoids.[1]

Evidence and where the guidelines stop

The evidence base for Grover's is dominated by retrospective case series, expert opinion and small uncontrolled trials; there are no large randomised controlled trials of any therapy. Mechanistic understanding has advanced substantially with the 2025 J Invest Dermatol review linking the SERCA-calcium-pump axis to Grover's, Darier's and Hailey-Hailey, and pointing toward SERCA-targeted small molecules as a future disease-modifying approach.[6]

There is no Grover's-specific guideline from the AAD, BAD or EDF. The framework is borrowed from the atopic dermatitis, psoriasis and acne guidelines that cover topical steroids, calcineurin inhibitors, phototherapy and oral retinoids. Phototherapy availability varies regionally: NHS and ANZ services have well-developed NB-UVB and PUVA; in resource-limited settings, tetracyclines or oral retinoids become the primary systemic options. Case reports of omalizumab (anti-IgE) and dupilumab (anti-IL-4/13) in refractory Grover's have appeared; these remain experimental and reserved for tertiary care with informed consent.[1]

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Mnemonics and the viva answer

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The mantra: Cool the man, biopsy a fresh lesion, send DIF — if the DIF is negative, the four-pattern histology does the rest.[1]

Etymology for viva gold: acantholysis is Greek akantha (thorn, later "prickle cell") plus lysis (loosing) — the prickle cells let go of each other. Grover is just the man; the disease is one of dermatology's few eponyms that admits its own discoverer without metaphor.[2]

Ward-round test — three stems, thirty seconds each

Stem 1 — the itchy man on the orthopaedic ward (answer)

A 68-year-old man, day five after a hemiarthroplasty, has erupted over forty-eight hours with intensely itchy papules on the central chest and upper back. Face, palms, soles and mouth are spared. What is the diagnosis, and what single test settles it? Model: This is Grover's disease (transient acantholytic dermatosis) in its classic scenario — heat, sweat, occlusion under drapes, xerosis and immobility in an older man, with the truncal distribution and striking sparing of face, palms, soles and mucosa. The single settling test is a 4 mm punch biopsy of a fresh, intact, under-48-hour-old papulovesicle, sent for H&E and DIF: focal acantholysis, often with mixed patterns, and a negative DIF clinch it. Order cooling, emollient and a mid-potency topical steroid (betamethasone valerate 0.1% BD) now, and mobilise.[1]

Stem 2 — the negative DIF you forgot to send (answer)

A 72-year-old woman has a persistent, crusted, occasionally blistering truncal eruption for eight months, treated empirically as eczema with potent topical steroids. She has done steadily worse. What went wrong? Model: No DIF was sent. A persistent acantholytic dermatosis treated blindly as eczema may in fact be pemphigus foliaceus (intercellular IgG/C3 on DIF, positive anti-Dsg1 ELISA), bullous pemphigoid (linear IgG/C3 at the basement membrane) or paraneoplastic acantholytic dermatosis. The recurring trainee error is treating an unbiopsied chronic blistering eruption with steroids, which partially suppresses pemphigus and delays the diagnosis. Send DIF and anti-desmoglein ELISA, screen for haematological malignancy if features fit, and involve dermatology before any further empirical escalation.[1]

Stem 3 — the punch in the mouth (answer)

A 65-year-old man labelled "Grover's" develops painful oral erosions and a positive Nikolsky sign over forty-eight hours. What is the diagnosis, and what is the first action? Model: This is not Grover's. Grover's spares the oral mucosa and has a negative Nikolsky. Painful oral erosions plus a positive Nikolsky in an acantholytic eruption is pemphigus vulgaris until proven otherwise — admit, send DIF (intercellular IgG/C3) and anti-desmoglein 3 ELISA, and involve dermatology urgently for systemic therapy (prednisolone plus rituximab in modern regimens). Untreated pemphigus vulgaris is fatal; the negative-DIF rule exists precisely so this mislabelling does not happen.[1]

References

1. [1]Weaver J, Bergfeld WF Grover disease (transient acantholytic dermatosis) Arch Pathol Lab Med, 2009.PMID 19722762
2. [2]Grover RW Transient acantholytic dermatosis Arch Dermatol, 1970.PMID 5440816
3. [3]Heenan PJ, Quirk CJ Transient acantholytic dermatosis Br J Dermatol, 1980.PMID 7387898
4. [4]Lockwood RR, Elias PM Transient acantholytic dermatosis Arch Dermatol, 1977.PMID 931408
5. [5]Wolff HH Transient acantholytic dermatosis (Grover) Hautarzt, 1977.PMID 845033
6. [6]Harmon RM, Ayers JL, McCarthy EF Pumping the Breaks on Acantholytic Skin Disorders: Targeting Calcium Pumps, Desmosomes, and Downstream Signaling in Darier, Hailey-Hailey, and Grover Disease J Invest Dermatol, 2025.PMID 39207315